Abstract
Background
Colorectal cancer (CRC) incidence and mortality in those aged 50 years and above have decreased over the past 2 decades. However, there is a rising incidence of CRC among individuals under 50 years of age, termed early-onset colorectal cancer (EOCRC). Patients with EOCRC are diagnosed at an advanced stage and may be in more psychosocial, emotional, and financial distress.
Objective
Our study examined the epidemiological shifts in CRC in Singapore, a multiethnic country.
Methods
CRCs diagnosed at age 20 years and above were identified from the Singapore Cancer Registry (SCR) from 1968 to 2019. Patient characteristics included gender, ethnicity, and age of CRC diagnosis. Population information was obtained from the Department of Statistics Singapore (SingStat). Age-specific incidence rates (ASRs) and age-standardized incidence rates (ASIRs) were calculated. The cohort was divided into 3 age groups: 20-49, 50-64, and ≥65 years. Temporal trends in incidence rates were modeled with joinpoint regression. Birth cohort models were fitted using the National Cancer Institute (NCI) age-period-cohort analysis tool. Cancer-specific survival analysis was performed with the Cox proportional hazards model.
Results
In total, 53,044 CRCs were included, and 6183 (11.7%) adults aged 20-49 years were diagnosed with EOCRC. The ASR of EOCRC rose from 5 per 100,000 population in 1968 to 9 per 100,000 population in 1996 at 2.1% annually and rose to 10 per 100,000 population in 2019 at 0.64% annually. The ASR for CRC among adults aged 50-64 years rose at 3% annually from 1968 to 1987 and plateaued from 1987, while the ASR for adults aged 65 years and above rose at 4.1% annually from 1968 to 1989 and 1.3% annually from 1989 to 2003 but decreased from 2003 onwards at 1% annually. The ASR of early-onset rectal cancer increased significantly at 1.5% annually. There was a continued rise in the ASR of EOCRC among males (annual percentage change [APC] 1.5%) compared to females (APC 0.41%). Compared to the 1950-1954 reference birth cohort, the 1970-1984 birth cohort had a significantly higher incidence rate ratio (IRR) of 1.17-1.36 for rectal cancer, while there was no significant change for colon cancer in later cohorts. There were differences in CRC trends across the 3 ethnic groups: Malays had a rapid and persistent rise in the ASR of CRC across all age groups (APC 1.4%-3%), while among young Chinese, only the ASR of rectal cancer was increasing (APC 1.5%). Patients with EOCRC had better survival compared to patients diagnosed at 65 years and above (hazard ratio [HR] 0.73, 95% CI 0.67-0.79, P<.001) after adjusting for covariates.
Conclusions
The rise in the incidence of rectal cancer among young adults, especially among Chinese and Malays, in Singapore highlights the need for further research to diagnose CRC earlier and reduce cancer-related morbidity and mortality.
Keywords: early-onset colorectal cancer, epidemiology, Singapore, joinpoint regression, age-period-cohort, public health, health disparity
Introduction
Colorectal cancer (CRC) presents a significant health care problem as it is the third-most common cancer diagnosed and the second-leading cause of death worldwide. In 2020, CRC accounted for 10% of the worldwide cancer incidence and 9% of cancer deaths. Currently, 2 million new cases are diagnosed annually worldwide, which is projected to rise to 3.2 million per annum by 2040 [1,2].
With the implementation of population-wide, average risk CRC screening for all adults aged 50 years or above, CRC incidence and mortality in this age group have progressively decreased over the past 2 decades. However, there is emerging evidence that the incidence of CRC in people under 50 years of age is rising, especially in high-income countries. Based on the World Health Organization–International Agency of Research on Cancer Incidence in Five Continents Plus database, the incidence of early-onset colorectal cancer (EOCRC) rose in 27 (54%) of 50 countries, with the highest incidence rates of 14-16 per 100,000 person-years seen in the United States, Australia, New Zealand, and South Korea [3]. In United States, since the 1990s, colon and rectal cancer incidence has been increasing at 1.3% and 2.3% per year, respectively, for adults aged 40-49 years [4]. This is in contrast to the declining incidence of CRC among adults aged 55 years or older. Similar trends in colon and rectal cancer incidence were observed in Australia, with an increase of 1.7% and 0.9% per year, respectively, for adults aged 40-49 years [5].
EOCRC may be associated with hereditary syndromes, such as Lynch syndrome and familial adenomatous polyposis, but these only account for 1%-3% of the total number of new CRC cases. The large majority of EOCRC cases are still sporadic and contribute 10%-12% of new CRC cases. EOCRC is more likely to occur in the left colon, with higher rates of mucinous and poorly differentiated cancers, which may be associated with poor prognosis [6]. Patients with EOCRC tend to possess an underappreciation of symptoms; more reluctance to seek medical assistance, leading to delayed diagnosis; and more advanced stage at diagnosis [7]. They present with unique challenges—as younger patients with young children, heavy financial commitments, and fertility preservation [8]. The rise in the incidence of EOCRC may be a consequence of increased endoscopic capacity, which may lower the threshold for performing colonoscopy in younger patients. However, another important factor is the strong birth cohort effect observed worldwide, which may be the result of changes in exposure to risk factors. Although most studies have found EOCRC prevalence to be independent of gender, racial disparities in EOCRC incidence have been described in the United States, with a higher incidence seen in African Americans [9,10].
Singapore has a multiethnic resident population of 4 million, of which 74% are Chinese, 13% Malays, and 9% Indians [11]. In Singapore, CRC has the highest incidence among all cancers for the past several years, which, therefore, imposes a substantial burden in terms of complications, mortality, health care resources, and medical costs [12]. According to the Singapore Cancer Registry Annual Report 2021, there were a total of 12,239 new cases of CRC diagnosed from 2017 to 2021. There was a notable rise in the age-standardized incidence rate (ASIR) of CRC from 19.4 per 100,000 population in 1968-1972 to 37.5 per 100,000 population in 2017-2021 among men. A similar trend among females was observed, at 15.4 per 100,000 population in 1968-1972 to 26.9 per 100,000 population in 2017-2021. Among those aged 40-49 years, CRC was the most common cause of cancer among men and the fourth-most common cause of cancer among women. There were differing trends in the ASIRs of cancer among the 3 main ethnic groups. Although the Chinese had the highest ASIR of cancer throughout the years, there is evidence of a closing ethnic gap in cancer incidence between the Chinese and Malays [13]. Although there has been an overall increase in survival rates for CRC over the past decades, the age-specific patterns and effects of gender and ethnicity on the incidence trends in CRC in Singapore are not well studied. Therefore, the aim of this study was to perform a comprehensive analysis of temporal trends in colon and rectal cancer incidence in Singapore.
Methods
Study Design and Data Source
The Singapore Cancer Registry (SCR) is a population-based registry that was established in 1968 and is part of the National Registry of Disease Office. The SCR collects notifications from medical practitioners about all patients with cancer diagnosed in Singapore, as mandated by the National Registry of Diseases Act 2007. The data are internationally comparable and valid, with completeness of about 97.5%. Annual audits of the data are performed to ensure data accuracy of at least 95% as the data are critical to guide cancer prevention policies and cancer research [14].
Patients aged 20 years and older diagnosed with colon cancer (International Classification of Diseases [ICD]-9 code 153, ICD-10 code C18) and rectal cancer (ICD-9 codes 154.0, 154.1; ICD-10 codes C19.9, C20.9) from 1968 to 2019 from the SCR were included in this study. Recurrent and metachronous CRCs, premalignant tumors, carcinoma in situ, extranodal colorectal lymphoma, and sarcomas were excluded. Information about the Singapore population was obtained from the Department of Statistics Singapore (SingStat), which provides publicly available data that were used to define the denominator for incidence rates [11]. Patient characteristics included gender, ethnicity, and age at diagnosis. The tumor, node, and metastasis (TNM) stage at diagnosis was available for patients diagnosed from 2003 onward.
Colon cancers were separated from cancers of the rectosigmoid and rectum, which were grouped together as rectal cancer for analysis. Age-specific incidence rates (ASRs) were calculated as the number of new CRC cases diagnosed each year divided by the population at risk for that age group. The population at risk was defined as the group of individuals susceptible to CRC during the period of interest. ASIRs were calculated as the sum of weighted ASRs using the direct method and the Segi-Doll World Standard as the reference population.
Joinpoint Analysis
The cohort was initially divided into 3 age groups: 20-49, 50-64, and ≥65 years. EOCRC was defined as CRC diagnosed at age 20-49 years. Annual incidence rates from 1968 to 2019 were estimated for the 3 age groups. Joinpoint regression analysis was used to describe the temporal trends in cancer incidence, identify points of change in direction, and estimate the magnitude of the change in rates. Joinpoint analysis estimates the annual percentage change (APC) by assessing observed data and fitting a series of joined straight lines to determine the APC over each period. The changes are tested for statistical significance [15,16]. It assumes that the regression function is piecewise linear, and the segments are continuously connected at unknown change points [17]. Compared to the traditional Monte Carlo permutation method, the data-driven weighted Bayes information criterion (BIC) was used for model selection as it was computationally more efficient yet produced similar results [18].
Age-Period-Cohort Modeling
Birth cohort models were fitted using the National Cancer Institute (NCI) Age Period Cohort web tool [19]. Age-period-cohort modeling provides estimates of parameters that describe relationships between observed incidence rates and age, calendar period, and birth cohort based on age groups and time periods of equal length. There was no information available for those aged ≥70 years for several time points from SingStat population estimates. Therefore, age-period-cohort analysis was limited to those aged 20-69 years. Input data were CRC cases and population counts for 10 five-year time periods (1970-1974, 1975-1979, …, 2015-2019), 10 five-year age groups (20-24, 25-29, …, 65-69 years), and 19 birth cohorts generated starting from the 1905-1909 to the 1995-1999 birth cohort. Cohort effects were presented as incidence rate ratios (IRRs) for a given birth cohort, with the 1950-1954 as the reference birth cohort. Additionally, local drifts estimated the age-specific net APC in incidence rates across the different age groups.
Survival Analysis
Cancer-specific survival was defined as the period from the date of CRC diagnosis to the date of death due to CRC. Patients who died of other causes were censored at their date of death; similarly, patients who were still alive were censored at the date of last follow-up. Clinical characteristics, such as surgical, radiation, and chemotherapy treatments received, were available. Multivariable survival analysis was performed with the Cox proportional hazards model.
Ethical Considerations
The study was approved by the SingHealth Institutional Review Board (IRB 2022/2415) to access and analyze data from the SCR. Informed consent was waived (waiver of consent was approved by the SingHealth IRB) as study data were deidentified.
Results
Characteristics of the Study Population
In total, 53,044 CRCs were included, with 32,880 (62%) colon and 20,164 (38%) rectal cancers. Figure 1 describes the flowchart of identifying and extracting patients from the SCR. Furthermore, 6183 (11.7%) EOCRCs were diagnosed, with 3585 (58%) colon and 2598 (42%) rectal cancers. Clinical characteristics of the study population are described in Table 1. There was a higher proportion of stage 3 (37.4% vs 32.4%) and stage 4 (26.1% vs 24%) CRCs and a lower proportion of stage 2 (21.2% vs 28.1%) CRCs among EOCRCs compared to patients diagnosed at an age of 65 years and above (P<.001).
Figure 1.
Flowchart of the patients identified and extracted from the SCR. ICD: International Classification of Diseases; SCR: Singapore Cancer Registry.
Table 1.
Characteristics of CRCsa from the SCRb.
| Characteristics | Total cases (N=53,044), n (%) | Group 1 (20-49 years; n=6183), n (%) | Group 2 (50-64 years; n=17,862), n (%) | Group 3 (≥65 years; n=28,999), n (%) | |
| Gender; P<.001 | |||||
|
|
Male | 28,429 (53.6) | 3235 (52.3) | 10,245 (57.4) | 14,949 (51.6) |
|
|
Female | 24,615 (46.4) | 2948 (47.7) | 7617 (42.6) | 14,050 (48.4) |
| Ethnicity; P<.001 | |||||
|
|
Chinese | 46,831 (88.3) | 5167 (83.6) | 15,495 (86.7) | 26,169 (90.2) |
|
|
Indian | 1767 (3.3) | 305 (4.9) | 671 (3.8) | 791 (2.7) |
|
|
Malay | 3723 (7.0) | 583 (9.4) | 1448 (8.1) | 1692 (5.8) |
|
|
Others | 723 (1.4) | 128 (2.1) | 248 (1.4) | 347 (1.2) |
| Tumor site; P<.001 | |||||
|
|
Colon | 32,880 (62) | 3585 (58.0) | 10,332 (57.8) | 18,963 (65.4) |
|
|
Rectum | 20,164 (38) | 2598 (42.0) | 7530 (42.2) | 10,036 (34.6) |
| TNMc stage (2003 and beyond); P<.001 | |||||
|
|
1 | 4436 (15.9) | 397 (15.3) | 1643 (16.6) | 2396 (15.6) |
|
|
2 | 7178 (25.7) | 551 (21.2) | 2299 (23.2) | 4328 (28.1) |
|
|
3 | 9495 (34) | 969 (37.4) | 3534 (35.6) | 4992 (32.4) |
|
|
4 | 6830 (24.4) | 677 (26.1) | 2448 (24.7) | 3705 (24.0) |
aCRC: colorectal cancer.
bSCR: Singapore Cancer Registry.
cTNM: tumor, node, and metastasis.
Joinpoint Regression Analysis of Incidence Rates of Colorectal, Colon, and Rectal Cancers
The ASIR of CRC rose from 15 in 1968 to 36 per 100,000 population in 1992 at an APC of 3.5% and plateaued (Figure 2). The ASIR of colon cancer rose from 8 in 1968 to 20 per 100,000 population in 1990 at an APC of 4.3% and plateaued. The ASIR of rectal cancer rose from 7 in 1968 to 14 per 100,000 population in 1990 at an APC of 2.5% and decreased to 12 per 100,000 population in 2019 at an APC of –0.5%.
Figure 2.
Joinpoint regression of the ASIR of CRC, colon cancer, and rectal cancer. APC: annual percentage change; ASIR: age-standardized incidence rate; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
The results of joinpoint regression are shown in Table 2 and Figure 3 for CRC, colon cancer, and rectal cancer stratified by age group. For EOCRC, the ASR rose from 5 in 1968 to 9 in 1997 at an APC of 2% and increased to 10 per 100,000 population in 2019 at an APC of 0.6%. For those aged 50-64 years, trends were similar to the ASIR of CRC for the overall Singapore population. For those aged 65 years and above, the ASR of CRC rose from 113 in 1968 to 299 in 2002 at an APC of 4.11% and decreased to 242 per 100,000 population in 2019 at an APC of –1.03%.
Table 2.
APCa of CRCb, colon cancer, and rectal cancer ASRsc by age group and tumor location. See Multimedia Appendix 1 for a high-resolution version.
| Type of cancer and age groups | Patients, n (%) | Trend 1 | Trend 2 | Trend 3 | ||||
|
|
|
|
Years | APC, % | Years | APC, % | Years | APC, % |
| CRC | ||||||||
|
|
20-49 years | 6183 (11.6) | 1968-1996 | 2.07d | 1996-2019 | 0.64d | —e | — |
|
|
50-64 years | 17,862 (33.7) | 1968-1987 | 2.97d | 1987-2019 | 0.09 | — | — |
|
|
≥65 years | 28,999 (54.7) | 1968-1989 | 4.11d | 1989-2003 | 1.30d | 2003-2019 | –1.03f |
| Colon cancer | ||||||||
|
|
20-49 years | 3585 (10.9) | 1968-1995 | 2.16d | 1995-2019 | 0.37 | — | — |
|
|
50-64 years | 10,332 (31.4) | 1968-1986 | 3.45d | 1986-2019 | 0.29d | — | — |
|
|
≥65 years | 18,963 (57.7) | 1968-1989 | 4.95d | 1989-2005 | 1.30d | 2005-2019 | –0.92f |
| Rectal cancer | ||||||||
|
|
20-49 years | 2598 (12.9) | 1968-2019 | 1.49d | — | — | — | — |
|
|
50-64 years | 7530 (37.3) | 1968-1992 | 1.97d | 1992-2019 | –0.34f | — | — |
|
|
≥65 years | 10,036 (49.8) | 1968-1996 | 2.67d | 1996-2019 | –1.15f | — | — |
aAPC: annual percentage change.
bCRC: colorectal cancer.
cASR: age-specific incidence rate.
dStatistically significant positive APCs.
eNot applicable.
fStatistically significant negative APCs.
Figure 3.
Joinpoint regression of the ASRs of CRC, colon cancer, and rectal cancer by age group and tumor location. APC: annual percentage change; ASR: age-specific incidence rate; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
The ASR of early-onset colon cancer rose from 3 in 1968 to 5 per 100,000 population in 1995 at an APC of 2.2% and thereafter had a nonsignificant increase at an APC of 0.4%. For those aged 50-64 years, colon cancer trends were similar to the ASIR of CRC for the overall Singapore population. For those aged 65 years and above, the ASR of colon cancer rose from 57 in 1968 to 193 in 2005 at an APC of 4.95% and decreased to 170 per 100,000 population in 2019 at an APC of –0.92%.
The ASR of early-onset rectal cancer rose from 2 in 1968 to 5 per 100,000 population in 2019 at an APC of 1.5% per year. For those aged 50-64 years and 65 years and above diagnosed with rectal cancer, trends were similar to the ASIR of rectal cancer for the overall Singapore population (Table 2 and Figure 3).
Effect of Gender
The male population had higher incidence rates for colon and rectal cancers. Similar to the ASIR, for both genders aged 50-64 years and 65 years and above, the incidence of CRC, colon cancer, and rectal cancer rose before it plateaued or decreased in the recent 2 decades (Table 3 and Figures 4 and 5). Among those aged 50-64 years, there was a rapid initial rise in colon cancer among women compared to men (APC 5% vs 3.8%).
Table 3.
APCa of CRCb, colon cancer, and rectal cancer ASRsc by age group, tumor location, and gender.
| Type of cancer and age groups | Patients, n (%) | Trend 1 | Trend 2 | Trend 3 | ||||
|
|
|
|
Years | APC, % | Years | APC, % | Years | APC, % |
| CRC (20-49 years) | ||||||||
|
|
Male | 3235 (52.3) | 1968-2019 | 1.48d | —e | — | — | — |
|
|
Female | 2948 (47.7) | 1968-1994 | 2.10d | 1994-2019 | 0.41 | — | — |
| CRC (50-64 years) | ||||||||
|
|
Male | 10,245 (57.4) | 1968-1989 | 3.34d | 1989-2019 | 0.11 | — | — |
|
|
Female | 7617 (42.6) | 1968-1980 | 4.20d | 1980-2019 | 0.04 | — | — |
| CRC (≥65 years) | ||||||||
|
|
Male | 14,949 (51.6) | 1968-1989 | 3.76d | 1989-2003 | 1.79 | 2003-2019 | –0.95 |
|
|
Female | 14,050 (48.4) | 1968-1981 | 6.18d | 1981-1999 | 2.17d | 1999-2019 | –1.01f |
| Colon cancer (20-49 years) | ||||||||
|
|
Male | 1715 (47.8) | 1968-2019 | 1.10d | — | — | — | — |
|
|
Female | 1870 (52.2) | 1968-1986 | 3.81d | 1986-2019 | 0.55d | — | — |
| Colon cancer (50-64 years) | ||||||||
|
|
Male | 5471 (53.0) | 1968-1988 | 3.76d | 1988-2019 | 0.34 | — | — |
|
|
Female | 4861 (47.0) | 1968-1980 | 4.99d | 1980-2019 | 0.19 | — | — |
| Colon cancer (≥65 years) | ||||||||
|
|
Male | 9289 (49.0) | 1968-1988 | 4.92d | 1988-2005 | 1.64 | 2005-2019 | –0.77 |
|
|
Female | 9674 (51.0) | 1968-1989 | 5.04d | 1989-2004 | 1.18d | 2004-2019 | –1.04f |
| Rectal cancer (20-49 years) | ||||||||
|
|
Male | 1520 (58.5) | 1968-2019 | 1.91d | — | — | — | — |
|
|
Female | 1078 (41.5) | 1968-2019 | 0.93d | — | — | — | — |
| Rectal cancer (50-64 years) | ||||||||
|
|
Male | 4774 (63.4) | 1968-1989 | 2.61d | 1992-2019 | –0.27 | — | — |
|
|
Female | 2756 (36.6) | 1968-2019 | 0 | — | — | — | — |
| Rectal cancer (≥65 years) | ||||||||
|
|
Male | 5660 (56.4) | 1968-2002 | 2.18d | 2002-2019 | –1.59f | — | — |
|
|
Female | 4376 (43.6) | 1968-1995 | 2.69d | 1995-2004 | –1.55f | — | — |
aAPC: annual percentage change.
bCRC: colorectal cancer.
cASR: age-specific incidence rate.
dStatistically significant positive APCs.
eNot applicable.
fStatistically significant negative APCs.
Figure 4.
Joinpoint regression of ASRs of CRC, colon cancer, and rectal cancer by gender (male: red; female: blue). APC: annual percentage change; ASR: age-specific incidence rate; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
Figure 5.
Joinpoint regression of ASRs of CRC, colon cancer, and rectal cancer by age group and gender (male: red; female: blue). APC: annual percentage change; ASR: age-specific incidence rate; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
For males aged 20-49 years, there was a rising incidence in CRC (APC 1.5%), mainly rectal cancer (APC 1.9%), with a smaller rise in colon cancer (APC 1.1%). For females aged 20-49 years, similar to older females aged 50-64 years, there was a rapid initial rise, particularly in colon cancer (APC 3.8%); however, in recent years, for colon cancer, rectal cancer, and CRC, the APC has been <1% (Table 3 and Figure 5).
Effect of Ethnicity
Similar to the ASIR, for Chinese patients aged 50-64 years and 65 years and above, the ASR of CRC, colon cancer, and rectal cancer showed an initial rise but plateaued or decreased in the recent 2 decades. In Malays across all 3 age groups, there was a persistent rise in the ASR of CRC, colon cancer, and rectal cancer (APC 1.4%-3.2%) without evidence of it plateauing. In Indians aged 50-64 years and 65 years and above, there was a smaller persistent rise in the ASR of CRC, colon cancer, and rectal cancer (APC 1%-1.4%) without evidence of it plateauing (Tables 4-6 and Figures 6 and 7).
Table 4.
APCa of CRCb, colon cancer, and rectal cancer ASRsc for patients diagnosed at age 20-49 years by tumor location and ethnicity.
| Tumor location and ethnicity | Patients, n (%) | Trend 1 | Trend 2 | Trend 3 | ||||
|
|
|
|
Years | APC, % | Years | APC, % | Years | APC, % |
| CRC | ||||||||
|
|
Chinese | 5167 (85.3) | 1968-1999 | 1.96d | 1999-2019 | 0.23 | —e | — |
|
|
Indian | 305 (5.1) | 1968-2019 | 0.47 | — | — | — | — |
|
|
Malay | 583 (9.6) | 1968-2019 | 2.90d | — | — | — | — |
| Colon cancer | ||||||||
|
|
Chinese | 2992 (85.4) | 1968-1999 | 1.75d | 1999-2019 | –0.09 | — | — |
|
|
Indian | 164 (4.7) | 1968-2019 | 0.03 | — | — | — | — |
|
|
Malay | 346 (9.9) | 1968-2019 | 1.96d | — | — | — | — |
| Rectal cancer | ||||||||
|
|
Chinese | 2175 (85.2) | 1968-2019 | 1.48d | — | — | — | — |
|
|
Indian | 141 (5.5) | 1968-2019 | 0.45 | — | — | — | — |
|
|
Malay | 237 (9.3) | 1968-2019 | 1.96d | — | — | — | — |
aAPC: annual percentage change.
bCRC: colorectal cancer.
cASR: age-specific incidence rate.
dStatistically significant positive APCs.
eNot applicable.
Table 6.
APCa of CRCb, colon cancer, and rectal cancer ASRsc for patients diagnosed at age ≥65 years by tumor location and ethnicity.
| Tumor location and ethnicity | Patients, n (%) | Trend 1 | Trend 2 | Trend 3 | ||||
|
|
|
|
Years | APC, % | Years | APC, % | Years | APC, % |
| CRC | ||||||||
|
|
Chinese | 26,169 (91.3) | 1968-1990 | 4.32d | 1990-2002 | 1.35d | 2002-2019 | –1.47e |
|
|
Indian | 791 (2.8) | 1968-2019 | 1.32d | —f | — | — | — |
|
|
Malay | 1692 (5.9) | 1968-2019 | 2.97d | — | — | — | — |
| Colon cancer | ||||||||
|
|
Chinese | 17,254 (92.0) | 1968-1990 | 5.21d | 1990-2003 | 1.35d | 2003-2019 | –1.26e |
|
|
Indian | 483 (2.6) | 1968-2019 | 1.38d | — | — | — | — |
|
|
Malay | 1006 (5.4) | 1968-2019 | 3.24d | — | — | — | — |
| Rectal cancer | ||||||||
|
|
Chinese | 8915 (90.0) | 1968-1996 | 2.93d | 1996-2019 | –1.60e | — | — |
|
|
Indian | 308 (3.1) | 1968-2019 | 0.99d | — | — | — | — |
|
|
Malay | 686 (6.9) | 1968-2019 | 1.88d | — | — | — | — |
aAPC: annual percentage change.
bCRC: colorectal cancer.
cASR: age-specific incidence rate.
dStatistically significant positive APCs.
eStatistically significant negative APCs.
fNot applicable.
Figure 6.
Joinpoint regression of ASIRs of CRC, colon cancer, and rectal cancer by ethnic group (Chinese/CN: blue; Indian/IN: green; Malay/MY: red). APC: annual percentage change; ASIR: age-standardized incidence rate; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
Figure 7.
Joinpoint regression of ASRs of CEC, colon cancer, and rectal cancer by age group, tumor location, and ethnic group (Chinese/CN: blue; Indian/IN: green; Malay/MY: red). APC: annual percentage change; ASR: age-specific incidence rate; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
Table 5.
APCa of CRCb, colon cancer, and rectal cancer ASRsc for patients diagnosed at age 50-64 years by tumor location and ethnicity.
| Tumor location and ethnicity | Patients, n (%) | Trend 1 | Trend 2 | Trend 3 | ||||
|
|
|
|
Years | APC, % | Years | APC, % | Years | APC, % |
| CRC | ||||||||
|
|
Chinese | 15,495 (88.0) | 1968-1985 | 3.45d | 1985-2019 | –0.12 | —e | — |
|
|
Indian | 671 (3.8) | 1968-2019 | 0.95d | — | — | — | — |
|
|
Malay | 1448 (8.2) | 1968-2019 | 2.30d | — | — | — | — |
| Colon cancer | ||||||||
|
|
Chinese | 9012 (88.4) | 1968-1981 | 5.57d | 1981-2019 | 0.13 | — | — |
|
|
Indian | 356 (3.5) | 1968-2019 | 1.22d | — | — | — | — |
|
|
Malay | 823 (8.1) | 1968-2019 | 2.69d | — | — | — | — |
| Rectal cancer | ||||||||
|
|
Chinese | 6483 (87.3) | 1968-1988 | 2.31d | 1988-2019 | –0.42f | — | — |
|
|
Indian | 315 (4.3) | 1968-2019 | 0.45 | — | — | — | — |
|
|
Malay | 625 (8.4) | 1968-2019 | 1.42d | — | — | — | — |
aAPC: annual percentage change.
bCRC: colorectal cancer.
cASR: age-specific incidence rate.
dStatistically significant positive APCs.
eNot applicable.
fStatistically significant negative APCs.
Malay patients aged 20-49 years had the highest rise in the ASR of CRC (APC 2.9%), colon cancer (APC 2%), and rectal cancer (APC 2%). Among Chinese patients aged 20-49 years, the ASR of rectal cancer persistently rose (APC 1.5%), while the ASR of CRC and colon cancer plateaued from 1999. In Indians aged 20-49 years, there was a small and nonsignificant rise in the ASR of CRC (APC 0.5%) and rectal cancer (APC 0.5%), as shown in Tables 4-6 and Figure 7.
Age-Period-Cohort Model of IRRs and APCs for CRC, Colon Cancer, and Rectal Cancer
Table 7 and Figure 8 show the IRRs by birth cohort for CRC, colon cancer, and rectal cancer. Compared to the reference birth cohort of 1950-1954, there was a trend toward higher IRRs for colon cancer among the 1970-1990 birth cohorts; however, these changes were not statistically significant. In addition, compared to the reference birth cohort of 1950-1954, the IRRs for rectal cancer among the birth cohorts from 1905 onward were marginally lower. However, there was significant increase in the IRR for rectal cancer among the birth cohorts from 1970 onward, and this peaked in the 1980-1984 birth cohort (IRR 1.35, 95% CI 1.043-1.748). Subsequent birth cohorts from 1985 onward had similar IRRs as the reference birth cohort (Figure 7 and Table 7).
Table 7.
IRRsa for CRCb, colon cancer, and rectal cancer by birth cohort.
| Birth cohort | CRC IRR (95% CI) | Colon cancer IRR (95% CI) | Rectal cancer IRR (95% CI) |
| 1905-1909 | 0.516 (0.435-0.613) | 0.434 (0.345-0.547) | 0.660 (0.503-0.867) |
| 1910-1914 | 0.697 (0.633-0.768) | 0.648 (0.570-0.736) | 0.781 (0.668-0.912) |
| 1915-1919 | 0.763 (0.706-0.825) | 0.696 (0.626-0.771) | 0.867 (0.765-0.983) |
| 1920-1924 | 0.761 (0.708-0.817) | 0.745 (0.679-0.817) | 0.784 (0.696-0.883) |
| 1925-1929 | 0.856 (0.802-0.912) | 0.846 (0.779-0.920) | 0.873 (0.784-0.972) |
| 1930-1934 | 0.889 (0.837-0.943) | 0.863 (0.799-0.933) | 0.929 (0.842-1.025) |
| 1935-1939 | 0.939 (0.889-0.993) | 0.916 (0.852-0.984) | 0.977 (0.892-1.070) |
| 1940-1944 | 0.948 (0.901-0.997) | 0.937 (0.878-1.000) | 0.966 (0.889-1.050) |
| 1945-1949 | 0.970 (0.926-1.015) | 0.956 (0.901-1.015) | 0.988 (0.915-1.067) |
| 1950-1954 | 1.000 (1.000) | 1.000 (1.000) | 1.000 (1.000) |
| 1955-1959 | 1.030 (0.986-1.075 | 1.047 (0.991-1.107) | 1.010 (0.940-1.086) |
| 1960-1964 | 1.006 (0.956-1.059) ) | 0.989 (0.925-1.057) | 1.030 (0.947-1.120) |
| 1965-1969 | 1.063 (0.998-1.133) | 1.047 (0.964-1.137) | 1.086 (0.978-1.205) |
| 1970-1974 | 1.091 (1.002-1.187) | 1.015 (0.907-1.136) | 1.199 (1.045-1.375) |
| 1975-1979 | 1.120 (0.999-1.255) | 1.016 (0.873-1.182) | 1.28 (1.067-1.541) |
| 1980-1984 | 1.172 (1.001-1.372) | 1.057 (0.858-1.302) | 1.35 (1.043-1.748) |
| 1985-1989 | 1.184 (0.940-1.491) | 1.251 (0.947-1.652) | 0.971 (0.623-1.512) |
| 1990-1994 | 1.266 (0.893-1.795) | 1.269 (0.841-1.914) | 1.031 (0.511-2.080) |
| 1995-1999 | 0.967 (0.517-1.807) | 0.951 (0.443-2.040) | 0.884 (0.280-2.792) |
aIRR: incidence rate ratio.
bCRC: colorectal cancer.
Figure 8.
IRRs by birth cohort for CRC, colon cancer, and rectal cancer. CRC: colorectal cancer; IRR: incidence rate ratio. See Multimedia Appendix 1 for a high-resolution version.
Figure 9 shows the net age-specific APC or local drift for CRC, colon cancer, and rectal cancer incidence rates. There was an increase in the incidence rates for CRC among those aged 25-69 years, with an average APC of 0.61% (95% CI 0.44-0.79) for all age groups over the entire period. There was an increase in incidence rates for colon cancer among those aged 40-69 years, while there was an increase in incidence rates for rectal cancer among those aged 35-69 years.
Figure 9.
Age-specific APC (local drift) for CRC, colon cancer, and rectal cancer. APC: annual percentage change; CRC: colorectal cancer. See Multimedia Appendix 1 for a high-resolution version.
Survival Outcomes
Patients with EOCRC had better cancer-specific survival compared to patients diagnosed at 65 years and above (hazard ratio [HR] 0.73, 95% CI 0.67-0.79, P<.001) after adjusting for the TNM stage, gender, tumor site, surgery, radiotherapy, and chemotherapy (Table 8).
Table 8.
Multivariable cancer-specific survival analysis of patients with CRCa using the Cox proportional hazards model.
| Variables and groups | HRb (95% CI) | P value | ||
| Age (years) | ||||
|
|
20-49 vs ≥65 | 0.73 (0.67-0.79) | <.001 | |
|
|
50-64 vs ≥65 | 0.74 (0.70-0.78) | <.001 | |
| TMNc stage | ||||
|
|
2 vs 1 | 3.84 (3.23-4.56) | <.001 | |
|
|
3 vs 1 | 11.14 (9.43-13.16) | <.001 | |
|
|
4 vs 1 | 58.70 (49.66-69.38) | <.001 | |
| Gender: male vs female | 1.06 (1.02-1.11) | .006 | ||
| Tumor site: rectum vs colon | 0.55 (0.52-0.58) | <.001 | ||
| Treatment | ||||
|
|
Surgery vs no surgery | 0.43 (0.41-0.46) | <.001 | |
|
|
Radiotherapy vs no radiotherapy | 1.10 (1.01-1.19) | <.026 | |
|
|
Chemotherapy vs no chemotherapy | 0.54 (0.51-0.57) | <.001 | |
aCRC: colorectal cancer.
bHR: hazard ratio.
cTNM: tumor, node, and metastasis.
Discussion
Principal Findings
Historically, CRC has been more commonly associated with older age groups, but in recent years, many countries have reported a concerning rise in cases among younger individuals. Although the overall incidence of CRC has been declining in older people, there has been a notable increase in the incidence of EOCRC, particularly in individuals younger than 50 years. In the United States, the overall annual, CRC ASIR has decreased by 46% from 66.2 per 100,000 population in 1985 to 35.7 per 100,000 population in 2019. Notably, CRC is now the most common cause of cancer deaths among individuals less than 50 years old [20]. However, from 2011 through 2019, the CRC incidence rate increased by 1.9% per year for individuals younger than 50 years. Rectal cancer has driven the EOCRC epidemiological trend with an increase of 2% per year. There was a steep decline in incidence among adults aged 50 years and older in the United States at 3%-5% annually in the late 2000s, and this is likely attributed to changing patterns in the risk factors and uptake of CRC screening. Incidence rates have been increasing in adults aged 20-39 years since the mid-1980s and in those aged 40-54 years since the mid-1990s [21]. Similar trends are seen in Canada, the United Kingdom, Australia, New Zealand, Europe, and Asia [5,22-25]. The rising incidence of EOCRC in East Asia may be due to an increase in the prevalence of risk factors, such as smoking, alcoholism, and obesity among young individuals [26]. A population-based study in Taiwan, Korea, Japan, and Hong Kong suggests that from 1995 to 2014, the pooled incidence of early-onset colon and rectal cancers increased by 2.1% and 3.8%, respectively, among men. Similarly, the pooled incidence of early-onset colon and rectal cancers increased by 2.2% and 4%, respectively, among women [27]. In China, the incidence rate of EOCRC rose from 3.6 to 12.1 per 100,000 population from 1990 to 2019 at a rate of 4.6% per year [25].
Our analysis of incidence trends over time suggests that the rising incidence of EOCRC in Singapore is nuanced. The rising trend for people under 50 years of age is particularly for rectal cancer, especially in males. This trend also affects, in particular, the Malays but also the Chinese, with the Indians less affected. Our study supports the increasing literature that the increase in EOCRC is not confined to the West and may be a worldwide phenomenon. The cause of these observations is still unclear, but it can be explained by the cohort effects. The IRR for rectal cancer has been increasing among the 1970-1984 birth cohorts and suggests that it is the changes in exposure to these birth cohorts that influence the risk of carcinogenesis. High consumption of processed meat, alcohol, a sedentary lifestyle, a lack of dietary fiber consumption, smoking, and obesity are known lifestyle factors associated with CRC. However, these modifiable risk factors are present in all age groups and not specific to young individuals and cannot explain fully the rising incidence among young people [28,29]. It has also been reported that there are similar rates of obesity between EOCRC and older patients with CRC [30]. The increasing prevalence of the use of antibiotics and alterations in the gut microbiome may play a role in the development of CRC through effects of bacterial-derived metabolites and virulence factors. Results of a recent study show an increase in Fusobacterium spp. in the microbiome of EOCRC [31]. Understanding the generational shifts in early life exposures may provide further insights into the etiologies of EOCRC [7].
Most tumors in EOCRC are in the sigmoid colon and rectum [32]. The reasons regarding the steep rise in the incidence of rectal compared to colon cancer among young adults are unclear. Understanding the differences in the molecular profile between rectal and colon cancers may be key toward developing preventative strategies. EOCRC in young adults has been associated with synchronous and metachronous tumors, a more poorly differentiated histology, and mucinous and signet ring histology compared to older patients [7,33]. The rates of high microsatellite instability (MSI-H) are higher in EOCRC due to the higher incidence of Lynch syndrome. However, among the microsatellite-stable (MSS) cohort of metastatic CRC, patients with EOCRC have lower rates of KRAS and BRAF V600 mutations [31]. These observations suggest that the underlying biological process and basis of these clinicopathological conditions in EOCRC are different from those found in people above 50 years old.
The male gender is associated with a higher incidence of CRC compared to females. The incidence of rectal cancer is higher among young males compared to females. In 2019, the incidence rate of early-onset rectal cancer was 6.2 per 100,000 population among men, while it was 3.6 per 100,000 population among women. The higher proportion of men diagnosed with rectal cancer suggests a differential distribution of the tumor location between genders. Although the etiology between the gender differences is uncertain, it may be attributed to the varied exposure in dietary and lifestyle risk factors between both gender groups [34]. Some studies have explored the protective effect of estrogens and progestins against CRC in hormone replacement therapy in postmenopausal women [35,36].
The Chinese population in Singapore had the highest ASIR of CRC when compared to Indians and Malays. Previously, the Asia Pacific Consensus identified Chinese as an ethnic group that is more susceptible to CRC, and this was supported by cohort studies in Singapore and Malaysia [37-40]. In this study, although the incidence initially increased among the Chinese, the incidence rates have plateaued and declined over the past decade, except for early-onset rectal cancer, which continues to rise at 1.5% per year among young Chinese adults. However, the steep increase in the incidence of both colon and rectal cancers among the Malays across all age groups is concerning. This observation is supported by another study of age-period-cohort analyses in the SCR, stratified by ethnicity, that suggests a rising risk of CRC across all periods among the Malay population [41]. The rising incidence of EOCRC predominantly among Malays was also observed in Malaysia [42]. The varied epidemiologic trends across the 3 ethnic groups may be attributed to the differences in health-seeking behavior and lifestyle exposures between the groups in Singapore [41]. Modifiable risk factors, such as the rising rates and high prevalence of obesity among the Malays and the increased consumption of sweetened food, may play a role [43]. Malays were also less likely to participate in cancer screening compared to the Chinese. There is a need for tailored cancer-screening promotion campaigns to narrow the knowledge-behavior gap among the Malays [44]. Socioeconomic indicators, such as educational attainment, homeownership rates, and income levels, have shown improvement across all racial groups in Singapore [45]. Although there is a relatively similar socioeconomic environment in Singapore, the varying rates of the rise of EOCRC among the 3 races suggest that cultural, dietary, or genetic factors may potentially contribute to these differences. Further studies should be conducted that compare the lifestyle factors and social practices among the 3 ethnic groups and evaluate the impact on CRC incidence.
Our study suggests that patients with EOCRC have better cancer-specific survival compared to patients with CRC aged 65 years and older. However, there are conflicting data with regard to the survival outcomes of EOCRC compared to patients with late-onset CRC after adjustment for stage. A survival analysis of 35,713 patients with stage 3 colon cancer from the ACCENT database revealed that patients with EOCRC have improved overall survival, disease-free survival, and survival after recurrence. After adjusting for molecular markers (MMR, KRAS, BRAF), the prognostic impact of age of onset was lost [46]. However, there was a poorer 3-year relapse-free survival among patients with stage 3 EOCRC based on the pooled analyses of 16,349 patients from the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) database. This was despite better treatment adherence and higher administered treatment intensity among the younger patients, hence suggestive of a more aggressive disease biology [47].
The current screening guidelines for CRC in Singapore start at 50 years of age for asymptomatic, average-risk individuals and have no impact on the incidence of early-onset CRC. Recently, the American Cancer Society recommended initiating CRC screening at age 45 years instead of 50 years for average-risk individuals to address the rising CRC incidence among young adults [48]. This recommendation was based on modeling data that suggest that this will prevent 29,400 CRC cases and 11,000 CRC deaths in the United States over the next 5 years [49]. Compared to the rising incidence of colon and rectal cancers in the United States, Europe, and Australia, our study suggests that rectal cancer among young adults is rising. Therefore, it is important for physicians to investigate young adults who present with anorectal symptoms, such as rectal bleeding, tenesmus, anal pain, and changes in bowel habits. Although these findings may suggest a need to re-evaluate the recommended age range for screening and consider extending screening to those 45-49 years of age, the incidence of EOCRC in Singapore remains low, and this strategy may not be cost effective. Despite the launch of the National Colorectal Screening Programme in 2011, the uptake of CRC screening remains low nationally at 41.7% [50,51]. However, flexible sigmoidoscopy among young adults is a less costly alternative as compared to colonoscopy and may capture the majority of EOCRCs since the tumor location of EOCRC is usually in the sigmoid colon or the rectum.
Strengths and Limitations
Although this study provides a comprehensive overview of CRC trends in Singapore, further research into the biological basis of carcinogenesis among young adults and differences in modifiable risk factors among ethnic groups is warranted. Age-period-cohort analysis was limited due to missing population data of those aged 70 years and above. Additionally, the study was limited due to the lack of information about the proportion of hereditary cancer syndromes in the cohort. The prevalence of hereditary cancer syndromes among EOCRCs ranges from 5% to 35% compared to 2%-5% for CRCs overall [52-55]. Although genetic predisposition may be associated with EOCRC, the majority of EOCRCs are still sporadic. Additionally, screening of families with hereditary cancer syndromes may only capture a small proportion of EOCRCs [52]. Future research should focus on identification of risk factors and predictors of EOCRC to determine high-risk groups that should be targeted for screening before 50 years of age. It may be a more viable strategy to develop risk stratification tools that combine family history and blood-based tests to identify high-risk neoplasia among young adults.
Conclusion
The incidence of rectal cancer among people under 50 years of age in Singapore appears to be increasing, especially among the Chinese and Malays. The differences in the epidemiologic trends among the 3 main ethnic groups may be due to varied lifestyle factors and social practices. Although it is possible that the observed increase may be attributable to lifestyle changes in the population over time, further studies are required to determine the underlying etiology. In contrast, CRC rates are decreasing among those above 65 years of age, and this may be due to the impact of the national screening program. These findings suggest the need for further research to diagnose CRC earlier among young adults and reduce the associated cancer-related morbidity and mortality.
Acknowledgments
The authors would like to acknowledge the National Registry of Diseases Office, Health Promotion Board, Singapore, for providing access to colorectal cancer data from the Singapore Cancer Registry. CHLR is supported by the Research Training Fellowship (MOH-001300-00) from the National Medical Research Council Singapore. The work was also supported by the Goh Hak Su Professorship in Colorectal Surgery.
Abbreviations
- APC
annual percentage change
- ASR
age-specific incidence rate
- ASIR
age-standardized incidence rate
- CRC
colorectal cancer
- EOCRC
early-onset colorectal cancer
- HR
hazard ratio
- ICD
International Classification of Diseases
- IRR
incidence rate ratio
- SCR
Singapore Cancer Registry
- SingStat
Department of Statistics Singapore
- TNM
tumor, node, and metastasis
High-resolution versions of Figures 2-9.
Data Availability
Data collected from the Singapore Cancer Registry are not available publicly.
Footnotes
Authors' Contributions: The authors attest that there was no use of generative artificial intelligence in the generation of text, figures, or other content of this manuscript.
Conflicts of Interest: None declared.
References
- 1.Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol. 2021 Oct;14(10):101174. doi: 10.1016/j.tranon.2021.101174. https://linkinghub.elsevier.com/retrieve/pii/S1936-5233(21)00166-2 .S1936-5233(21)00166-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Rabeneck L, Chiu H, Senore C. International perspective on the burden of colorectal cancer and public health effects. Gastroenterology. 2020 Jan;158(2):447–452. doi: 10.1053/j.gastro.2019.10.007.S0016-5085(19)41444-3 [DOI] [PubMed] [Google Scholar]
- 3.Sung H, Siegel RL, Laversanne M, Jiang C, Morgan E, Zahwe M, Cao Y, Bray F, Jemal A. Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data. Lancet Oncol. 2024 Dec 11;:S1470-2045. doi: 10.1016/S1470-2045(24)00600-4. https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(24)00600-4 .S1470-2045(24)00600-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233–254. doi: 10.3322/caac.21772. https://onlinelibrary.wiley.com/doi/10.3322/caac.21772 . [DOI] [PubMed] [Google Scholar]
- 5.Feletto E, Yu XQ, Lew J, St John DJB, Jenkins MA, Macrae FA, Mahady SE, Canfell K. Trends in colon and rectal cancer incidence in Australia from 1982 to 2014: analysis of data on over 375,000 cases. Cancer Epidemiol Biomarkers Prev. 2019 Jan;28(1):83–90. doi: 10.1158/1055-9965.EPI-18-0523.1055-9965.EPI-18-0523 [DOI] [PubMed] [Google Scholar]
- 6.Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):262–274. doi: 10.1016/s2468-1253(21)00426-x. [DOI] [PubMed] [Google Scholar]
- 7.Akimoto N, Ugai T, Zhong R, Hamada T, Fujiyoshi K, Giannakis M, Wu K, Cao Y, Ng K, Ogino S. Rising incidence of early-onset colorectal cancer - a call to action. Nat Rev Clin Oncol. 2021 Apr;18(4):230–243. doi: 10.1038/s41571-020-00445-1. https://europepmc.org/abstract/MED/33219329 .10.1038/s41571-020-00445-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Lieu CH, Golemis EA, Serebriiskii IG, Newberg J, Hemmerich A, Connelly C, Messersmith WA, Eng C, Eckhardt SG, Frampton G, Cooke M, Meyer JE. Comprehensive genomic landscapes in early and later onset colorectal cancer. Clin Cancer Res. 2019 Oct 01;25(19):5852–5858. doi: 10.1158/1078-0432.CCR-19-0899. https://europepmc.org/abstract/MED/31243121 .1078-0432.CCR-19-0899 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Saraiva MR, Rosa I, Claro I. Early-onset colorectal cancer: a review of current knowledge. World J Gastroenterol. 2023 Feb 28;29(8):1289–1303. doi: 10.3748/wjg.v29.i8.1289. https://www.wjgnet.com/1007-9327/full/v29/i8/1289.htm . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Pan H, Zhao Z, Deng Y, Zheng Z, Huang Y, Huang S, Chi P. The global, regional, and national early-onset colorectal cancer burden and trends from 1990 to 2019: results from the Global Burden of Disease Study 2019. BMC Public Health. 2022 Oct 12;22(1):1896. doi: 10.1186/s12889-022-14274-7. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-022-14274-7 .10.1186/s12889-022-14274-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Resident population by ethnic group, age group and sex dashboard. Department of Statistics Singapore. [2024-01-02]. https://www.singstat.gov.sg/find-data/search-by-theme/population/population-and-population-structure/visualising-data/resident-population-by-ethnic-group-age-group-and-sex-dashboard .
- 12.Lim GH, Chow KY, Lee HP. Singapore cancer trends in the last decade. Singapore Med J. 2012 Jan;53(1):3–9. http://smj.sma.org.sg/5301/5301ra1.pdf . [PubMed] [Google Scholar]
- 13.Singapore Cancer Registry Annual Report 2021. National Registry of Diseases Office. 2023. Aug, [2024-01-02]. https://nrdo.gov.sg/publications/cancer/
- 14.Fung JWM, Lim SBL, Zheng H, Ho WYT, Lee BG, Chow KY, Lee HP. Data quality at the Singapore Cancer Registry: an overview of comparability, completeness, validity and timeliness. Cancer Epidemiol. 2016 Aug;43:76–86. doi: 10.1016/j.canep.2016.06.006.S1877-7821(16)30077-7 [DOI] [PubMed] [Google Scholar]
- 15.Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2001 Feb 15;19(3):335–351. doi: 10.1002/(sici)1097-0258(20000215)19:3<335::aid-sim336>3.0.co;2-z.10.1002/(SICI)1097-0258(20000215)19:3<335::AID-SIM336>3.0.CO;2-Z [DOI] [PubMed] [Google Scholar]
- 16.Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating average annual per cent change in trend analysis. Stat Med. 2009 Dec 20;28(29):3670–3682. doi: 10.1002/sim.3733. https://europepmc.org/abstract/MED/19856324 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Kim H, Luo J, Kim J, Chen H, Feuer EJ. Clustering of trend data using joinpoint regression models. Stat Med. 2014 Oct 15;33(23):4087–4103. doi: 10.1002/sim.6221. https://europepmc.org/abstract/MED/24895073 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Kim H, Chen H, Midthune D, Wheeler B, Buckman DW, Green D, Byrne J, Luo J, Feuer EJ. Data-driven choice of a model selection method in joinpoint regression. J Appl Stat. 2023;50(9):1992–2013. doi: 10.1080/02664763.2022.2063265. https://www.tandfonline.com/doi/10.1080/02664763.2022.2063265?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub0pubmed .2063265 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Rosenberg PS, Check DP, Anderson WF. A web tool for age-period-cohort analysis of cancer incidence and mortality rates. Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2296–2302. doi: 10.1158/1055-9965.EPI-14-0300. https://europepmc.org/abstract/MED/25146089 .1055-9965.EPI-14-0300 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12–49. doi: 10.3322/caac.21820. https://onlinelibrary.wiley.com/doi/10.3322/caac.21820 . [DOI] [PubMed] [Google Scholar]
- 21.Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, Jemal A. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017 Aug 01;109(8):djw322. doi: 10.1093/jnci/djw322. https://europepmc.org/abstract/MED/28376186 .3053481 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Siegel RL, Torre LA, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019 Dec;68(12):2179–2185. doi: 10.1136/gutjnl-2019-319511.gutjnl-2019-319511 [DOI] [PubMed] [Google Scholar]
- 23.Chambers AC, Dixon SW, White P, Williams AC, Thomas MG, Messenger DE. Demographic trends in the incidence of young-onset colorectal cancer: a population-based study. Br J Surg. 2020 Apr;107(5):595–605. doi: 10.1002/bjs.11486. https://europepmc.org/abstract/MED/32149386 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Brenner DR, Ruan Y, Shaw E, De P, Heitman SJ, Hilsden RJ. Increasing colorectal cancer incidence trends among younger adults in Canada. Prev Med. 2017 Dec;105:345–349. doi: 10.1016/j.ypmed.2017.10.007. https://linkinghub.elsevier.com/retrieve/pii/S0091-7435(17)30357-2 .S0091-7435(17)30357-2 [DOI] [PubMed] [Google Scholar]
- 25.Li Q, Yu M, Lv H, Zhang L, Deng Y, Yu H. Burden of early-onset colorectal cancer along with attributable risk factors from 1990 to 2019: a comparative study between China and other G20 countries. BMC Public Health. 2023 Jul 31;23(1):1463. doi: 10.1186/s12889-023-16407-y. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-023-16407-y .10.1186/s12889-023-16407-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Huang J, Lucero-Prisno DE, Zhang L, Xu W, Wong SH, Ng SC, Wong MCS. Updated epidemiology of gastrointestinal cancers in East Asia. Nat Rev Gastroenterol Hepatol. 2023 May;20(5):271–287. doi: 10.1038/s41575-022-00726-3.10.1038/s41575-022-00726-3 [DOI] [PubMed] [Google Scholar]
- 27.Sung JJY, Chiu H, Jung K, Jun JK, Sekiguchi M, Matsuda T, Kyaw MH. Increasing trend in young-onset colorectal cancer in Asia: more cancers in men and more rectal cancers. Am J Gastroenterol. 2019 Feb;114(2):322–329. doi: 10.14309/ajg.0000000000000133. [DOI] [PubMed] [Google Scholar]
- 28.AlZaabi A, AlHarrasi A, AlMusalami A, AlMahyijari N, Al Hinai K, ALAdawi H, Al-Shamsi HO. Early onset colorectal cancer: challenges across the cancer care continuum. Ann Med Surg (Lond) 2022 Oct;82:104453. doi: 10.1016/j.amsu.2022.104453. https://linkinghub.elsevier.com/retrieve/pii/S2049-0801(22)01213-4 .S2049-0801(22)01213-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Lingas EC. Early-onset colon cancer: a narrative review of its pathogenesis, clinical presentation, treatment, and prognosis. Cureus. 2023 Sep;15(9):e45404. doi: 10.7759/cureus.45404. https://europepmc.org/abstract/MED/37854763 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Chen FW, Sundaram V, Chew TA, Ladabaum U. Advanced-stage colorectal cancer in persons younger than 50 years not associated with longer duration of symptoms or time to diagnosis. Clin Gastroenterol Hepatol. 2017 May;15(5):728–737.e3. doi: 10.1016/j.cgh.2016.10.038. https://europepmc.org/abstract/MED/27856366 .S1542-3565(16)31051-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Eng C, Jácome AA, Agarwal R, Hayat MH, Byndloss MX, Holowatyj AN, Bailey C, Lieu CH. A comprehensive framework for early-onset colorectal cancer research. Lancet Oncol. 2022 Mar;23(3):e116–e128. doi: 10.1016/S1470-2045(21)00588-X.S1470-2045(21)00588-X [DOI] [PubMed] [Google Scholar]
- 32.Bailey CE, Hu C, You YN, Bednarski BK, Rodriguez-Bigas MA, Skibber JM, Cantor SB, Chang GJ. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg. 2015 Jan;150(1):17–22. doi: 10.1001/jamasurg.2014.1756. https://europepmc.org/abstract/MED/25372703 .1920838 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Muller C, Ihionkhan E, Stoffel EM, Kupfer SS. Disparities in early-onset colorectal cancer. Cells. 2021 Apr 26;10(5):1018. doi: 10.3390/cells10051018. https://www.mdpi.com/resolver?pii=cells10051018 .cells10051018 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Nguyen SP, Bent S, Chen Y, Terdiman JP. Gender as a risk factor for advanced neoplasia and colorectal cancer: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2009 Jun;7(6):676–681.e1. doi: 10.1016/j.cgh.2009.01.008.S1542-3565(09)00050-0 [DOI] [PubMed] [Google Scholar]
- 35.Newcomb PA, Zheng Y, Chia VM, Morimoto LM, Doria-Rose VP, Templeton A, Thibodeau SN, Potter JD. Estrogen plus progestin use, microsatellite instability, and the risk of colorectal cancer in women. Cancer Res. 2007 Aug 01;67(15):7534–7539. doi: 10.1158/0008-5472.CAN-06-4275.67/15/7534 [DOI] [PubMed] [Google Scholar]
- 36.Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SAA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women's Health Initiative Investigators Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321–333. doi: 10.1001/jama.288.3.321.joc21036 [DOI] [PubMed] [Google Scholar]
- 37.Sung JJY, Lau JYW, Young GP, Sano Y, Chiu HM, Byeon JS, Yeoh KG, Goh KL, Sollano J, Rerknimitr R, Matsuda T, Wu KC, Ng S, Leung SY, Makharia G, Chong VH, Ho KY, Brooks D, Lieberman DA, Chan FKL, Asia Pacific Working Group on Colorectal Cancer Asia Pacific consensus recommendations for colorectal cancer screening. Gut. 2008 Aug;57(8):1166–1176. doi: 10.1136/gut.2007.146316. https://core.ac.uk/reader/37895907?utm_source=linkout .57/8/1166 [DOI] [PubMed] [Google Scholar]
- 38.Abu Hassan MR, Ismail I, Mohd Suan MA, Ahmad F, Wan Khazim WK, Othman Z, Mat Said R, Tan WL, Mohammed SRNS, Soelar SA, Nik Mustapha NR. Incidence and mortality rates of colorectal cancer in Malaysia. Epidemiol Health. 2016;38:e2016007. doi: 10.4178/epih.e2016007. https://europepmc.org/abstract/MED/26971697 .epih.e2016007 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Lee HP, Lee J, Shanmugaratnam K. Trends and ethnic variation in incidence and mortality from cancers of the colon and rectum in Singapore, 1968 to 1982. Ann Acad Med Singap. 1987 Jul;16(3):397–401. [PubMed] [Google Scholar]
- 40.Wong MC, Ding H, Wang J, Chan PS, Huang J. Prevalence and risk factors of colorectal cancer in Asia. Intest Res. 2019 Jul;17(3):317–329. doi: 10.5217/ir.2019.00021. https://europepmc.org/abstract/MED/31085968 .ir.2019.00021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Burkill S, Tan CS, Lau J, Koh GC, Tan KK. Colorectal cancer incidence in a multi-ethnic population: age-period-cohort analysis of trends in Singapore. Cancer Epidemiol. 2021 Dec;75:102046. doi: 10.1016/j.canep.2021.102046.S1877-7821(21)00163-6 [DOI] [PubMed] [Google Scholar]
- 42.Muhammad Nawawi KN, Mokhtar NM, Wong Z, Mohd Azman ZA, Hsin Chew DC, Rehir R, Leong J, Ismail F, Mohamed Rose I, Yaacob Y, Abdul Hamid H, Sagap I, Raja Ali RA. Incidence and clinicopathological features of colorectal cancer among multi-ethnic patients in Kuala Lumpur, Malaysia: a hospital-based retrospective analysis over two decades. PeerJ. 2021;9:e12425. doi: 10.7717/peerj.12425. https://europepmc.org/abstract/MED/34820182 .12425 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Zhang Y, Abdin E, Sambasivam R, Shafie S, Roystonn K, Vaingankar JA, Chong SA, Subramaniam M. Changes in body mass index and its association with socio-demographic characteristics between 2010 and 2016 in Singapore. Front Public Health. 2024;12:1374806. doi: 10.3389/fpubh.2024.1374806. https://europepmc.org/abstract/MED/38601489 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Chan TK, Tan LWL, van Dam RM, Seow WJ. Cancer screening knowledge and behavior in a multi-ethnic Asian population: the Singapore Community Health Study. Front Oncol. 2021;11:684917. doi: 10.3389/fonc.2021.684917. https://europepmc.org/abstract/MED/34476210 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Key socio-economic outcomes across cohorts. Ministry of Finance Singapore. 2019. Oct, [2024-01-02]. https://www.mof.gov.sg/docs/default-source/default-document-library/news-and-publications/press-releases/mof-report.pdf?sfvrsn=5eadc128_2> .
- 46.Jin Z, Dixon JG, Fiskum JM, Parekh HD, Sinicrope FA, Yothers G, Allegra CJ, Wolmark N, Haller D, Schmoll H, de Gramont A, Kerr R, Taieb J, Van Cutsem E, Tweleves C, O'Connell M, Saltz LB, Sadahiro S, Blanke CD, Tomita N, Seitz J, Erlichman C, Yoshino T, Yamanaka T, Marsoni S, Andre T, Mahipal A, Goldberg RM, George TJ, Shi Q. Clinicopathological and molecular characteristics of early-onset stage III Colon adenocarcinoma: an analysis of the ACCENT database. J Natl Cancer Inst. 2021 Nov 29;113(12):1693–1704. doi: 10.1093/jnci/djab123. https://europepmc.org/abstract/MED/34405233 .6353731 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Fontana E, Meyers J, Sobrero A, Iveson T, Shields AF, Taieb J, Yoshino T, Souglakos I, Smyth EC, Lordick F, Moehler M, Giraut A, Harkin A, Labianca R, Meyerhardt J, André T, Boukovinas I, Lonardi S, Saunders M, Vernerey D, Oki E, Georgoulias V, Ben-Aharon I, Shi Q. Early-onset colorectal adenocarcinoma in the IDEA Database: treatment adherence, toxicities, and outcomes with 3 and 6 months of adjuvant fluoropyrimidine and oxaliplatin. J Clin Oncol. 2021 Dec 20;39(36):4009–4019. doi: 10.1200/JCO.21.02008. https://europepmc.org/abstract/MED/34752136 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Wolf AMD, Fontham ETH, Church TR, Flowers CR, Guerra CE, LaMonte SJ, Etzioni R, McKenna MT, Oeffinger KC, Shih YT, Walter LC, Andrews KS, Brawley OW, Brooks D, Fedewa SA, Manassaram-Baptiste D, Siegel RL, Wender RC, Smith RA. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018 Jul;68(4):250–281. doi: 10.3322/caac.21457. https://onlinelibrary.wiley.com/doi/10.3322/caac.21457 . [DOI] [PubMed] [Google Scholar]
- 49.Ladabaum U, Mannalithara A, Meester RGS, Gupta S, Schoen RE. Cost-effectiveness and national effects of initiating colorectal cancer screening for average-risk persons at age 45 years instead of 50 years. Gastroenterology. 2019 Jul;157(1):137–148. doi: 10.1053/j.gastro.2019.03.023. https://europepmc.org/abstract/MED/30930021 .S0016-5085(19)33578-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Wong RK, Wong ML, Chan YH, Feng Z, Wai CT, Yeoh KG. Gender differences in predictors of colorectal cancer screening uptake: a national cross sectional study based on the health belief model. BMC Public Health. 2013 Jul 23;13:677. doi: 10.1186/1471-2458-13-677. https://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-13-677 .1471-2458-13-677 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.National Population Health Survey 2023 Report. Ministry of Health Singapore. 2024. Aug, [2024-01-02]. https://www.moh.gov.sg/others/resources-and-statistics/nphs-2023> .
- 52.Zaborowski AM, REACCT Collaborative Colorectal cancer in the young: Research in Early Age Colorectal Cancer Trends (REACCT) Collaborative. Cancers (Basel) 2023 May 30;15(11):2979. doi: 10.3390/cancers15112979. https://www.mdpi.com/resolver?pii=cancers15112979 .cancers15112979 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, Goldberg RM, Paskett E, Shields PG, Freudenheim JL, Stanich PP, Lattimer I, Arnold M, Liyanarachchi S, Kalady M, Heald B, Greenwood C, Paquette I, Prues M, Draper DJ, Lindeman C, Kuebler JP, Reynolds K, Brell JM, Shaper AA, Mahesh S, Buie N, Weeman K, Shine K, Haut M, Edwards J, Bastola S, Wickham K, Khanduja KS, Zacks R, Pritchard CC, Shirts BH, Jacobson A, Allen B, de la Chapelle A, Hampel H, Ohio Colorectal Cancer Prevention Initiative Study Group Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. 2017 Apr 01;3(4):464–471. doi: 10.1001/jamaoncol.2016.5194. https://europepmc.org/abstract/MED/27978560 .2593042 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Mork ME, You YN, Ying J, Bannon SA, Lynch PM, Rodriguez-Bigas MA, Vilar E. High prevalence of hereditary cancer syndromes in adolescents and young adults with colorectal cancer. J Clin Oncol. 2015 Nov 01;33(31):3544–3549. doi: 10.1200/JCO.2015.61.4503. https://europepmc.org/abstract/MED/26195711 .JCO.2015.61.4503 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Goel A, Nagasaka T, Spiegel J, Meyer R, Lichliter WE, Boland CR. Low frequency of Lynch syndrome among young patients with non-familial colorectal cancer. Clin Gastroenterol Hepatol. 2010 Nov;8(11):966–971. doi: 10.1016/j.cgh.2010.06.030. https://europepmc.org/abstract/MED/20655395 .S1542-3565(10)00676-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
High-resolution versions of Figures 2-9.
Data Availability Statement
Data collected from the Singapore Cancer Registry are not available publicly.
