Abstract
PURPOSE
Data from population-based studies have shown an increased incidence of certain types of neoplasms in patients younger than 50 years (early-onset cancer [EOC]); however, little information is derived from other real-world data sources. In a nonpopulation registry, we analyzed changes in the incidence of several neoplasms in successive generations.
METHODS
This cross-sectional study included all patients with a cancer diagnosis registered in one university hospital in Málaga, Spain, between 1998 and 2021, and 18 neoplasms were analyzed. For each neoplasm, the proportion of patients younger than 50 years and age 50 years and older (late-onset cancer [LOC]) of the total number of patients diagnosed each year was determined. In addition, the age limit was lowered to 45-40 years. Changes in these proportions between each year and the following year were assessed by calculating the annual percentage change (APC), and a final assessment of these changes was performed by determining the average APC (AAPC).
RESULTS
Of the 24,596 patients, 5,466 (22.2%) had EOC, and 19,130 (77.8%) had LOC. The incidence of all tumors increased throughout the study period in both age groups. The AAPC increase was higher in patients with EOC than in those with LOC for the following neoplasms: head and neck (6.1% v 4.6%), colon (11.0% v 8.2%), testicular (16.3% v –13.1%), non-Hodgkin lymphoma (8.4% v 5.9%), rectum (16.1% v 6.8%), kidney (27.8% v 20.1%), and sarcoma (43.4% v 28.6%). This increase was confirmed in patients younger than 45 years and 40 years.
CONCLUSION
Our results are consistent with the data published for most tumor sites analyzed. This global public health problem requires the utmost attention to decrease excess cancer in young patients.
INTRODUCTION
Cancer is commonly diagnosed in patients older than 50 years. However, using real-world data, an increase in the incidence of some types of cancer in younger patients has been observed. This problem has been defined as early-onset cancer (EOC) and includes any cancer diagnosed between age 20 and 49 years.1 This phenomenon has been identified since the early 1990s in different geographical areas worldwide, affecting countries with varying levels of development. The main types of malignancies in which this increasing incidence has been observed are colorectal, uterine corpus, gallbladder, esophageal, kidney, pancreatic, oral cavity and pharynx, liver, thyroid, multiple myeloma, gastric, and leukemia.1-13 Data from population-based registries in the United States with data from 1995 to 2014 showed that compared with the annual incidence rate for patients born in the 1950s, the annual incidence rate for patients born in the 1980s increased by 1.81 for colorectal cancer, 2.5 for uterine corpus cancer, 2.25 for pancreatic cancer, and 4.91 for kidney tumors.2 An analysis of the incidence of colorectal cancer worldwide between 2003 and 2012 concluded that in one group of countries (New Zealand, the United Kingdom, Canada, Australia, the United States, Germany, and Denmark), the incidence of colorectal cancer is decreasing in patients age 50 years and older, whereas an increase is observed in the annual incidence in patients younger than 50 years. In another group of countries where the incidence of colorectal cancer is increasing, the increase is greater in patients younger than 50 years (Korea, Cyprus, Turkey, the Netherlands, and Norway).5 Another study of registries from 48 countries conducted to analyze the changes in the incidence of pancreatic cancer between 2003 and 2012 found that the annual incidence increase was greater in patients younger than 50 years than in those age 50 years and older (New Zealand, Australia, Canada, the United States, Sweden, the United Kingdom, Switzerland, Germany, Turkey, and Spain).9
CONTEXT
Key Objective
Is it possible to verify with data available in our environment from a single hospital the increase in cancer incidence in patients younger than 50 years? This phenomenon has been identified since the 1990s in different parts of the world.
Knowledge Generated
In our patients, there is an increase of cancer cases in the population born in the last decades of the 20th century of greater magnitude than in previous generations.
Relevance
Our data contribute to the body of evidence on the early-onset cancer issue, which is already a significant problem today and will be a major problem in the future.
The underlying causes of this increase in sporadic cases in young patients are not fully understood. It is possible that screening programs could have played a role to a certain extent in some tumors, such as prostate or thyroid, but this relationship has only been observed in certain countries and, in addition, may not have been identified in other organs.1 Exposure to multiple risk factors during early life may have significant consequences by affecting the individual's risk of developing tumors in the future.14 These data are consistent with growing evidence that the earliest phases of carcinogenesis occur during childhood and young adulthood.15 These risk factors could be related to significant changes in the population's behavioral patterns during the second half of the 20th century. The different risk factors that would affect EOC are related to changes in diet (Western-style diet) and lifestyle (increase in sedentary lifestyle and physical inactivity, decrease in sleep hours), environmental changes, or changes in microbiota that could have occurred during childhood and adolescence.1 All these behavioral changes would increase the prevalence of obesity and the incidence of type 2 diabetes mellitus. Therefore, it is not surprising that most neoplasms observed in EOC are obesity-related cancers.16
This study analyzed the differences in the changes in the annual incidence of 18 types of neoplasms in patients age 20-49 years and age 50 years and older in a population of approximately one and a half million inhabitants during 24 years of follow-up. Furthermore, possible differences in the extent of neoplasia between the two age groups at the time of diagnosis were analyzed. In additional analyses, the age limit was lowered to 45 and 40 years for a detailed assessment of trends in younger individuals.
METHODS
Study Population
This descriptive cross-sectional study evaluated for inclusion all patients with a pathologic cancer diagnosis at an invasive stage who had at least one encounter at one of two university hospitals in Málaga, Spain (Hospital Regional Universitario and Hospital Universitario Virgen de la Victoria) between January 1, 1998, and December 31, 2021. A total of 1,500,000 people belong to the referral areas of both hospitals, representing 80% of the regional population. All patients with at least one encounter in either hospital were consistently digitally registered in our information system. This system is called Galen and includes, among other utilities, a database of patients and their electronic health records, with data on more than 65,000 patients and almost 67,000 neoplasms.17 Neoplasm-related data were prospectively entered into the system in a structured format by a medical oncologist during the first medical encounter. A data entry specialist subsequently reviewed the data to ensure accuracy. These neoplasm-related data are date of diagnosis (defined as first documented data of invasive cancer in a pathologic specimen), age at diagnosis (patient's age at the time of diagnosis date), organ involved (organ of the primary tumor site), histology (type of histology of the neoplasm), stage (stage of neoplasm), type of oncologic treatment (ie, surgery, chemotherapy, hormone therapy, and biologic treatments), and intention of oncologic treatment (ie, adjuvant, neoadjuvant, palliative, and follow-up). The 18 neoplasms included in our study were head and neck, cervical, colon, uterine corpus, esophagus, gastric, testicular, Hodgkin lymphoma, non-Hodgkin lymphoma, breast, melanoma, ovary, pancreas, lung, rectum, kidney, sarcoma, and biliary tree. These neoplasms were selected because of their incidence in our reference area and because they were adequately collected throughout the study period. Prostate neoplasms were not considered because only patients with advanced disease were included in our department and were, therefore, registered electronically.
This study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines for cross-sectional studies.18 The local research ethics committee approved this study and waived the requirement for informed consent.
Statistical Analysis
Categorical variables were described as frequencies and percentages and compared using the chi-square test and Fisher exact test, and continuous variables were expressed as means or medians. We analyzed the proportion of patients younger than 50 years and age 50 years and older (late-onset cancer [LOC]) of the total number of patients diagnosed each year during the study period for each neoplasm. Annual percentage change (APC) was calculated by taking the difference in incidence between one year and the next and calculating the corresponding percentage. The average APC (AAPC) was obtained by adding all the APC for each neoplasm and dividing by the total number of years of the study period. APC indicates the difference in a single time interval, while AAPC characterizes the global trend over the entire study period. Two additional analyses were performed using age thresholds at diagnosis lower than the EOC definition: younger than 45 years and 40 years.
All statistical analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria), and a P ≤ .05 was considered statistically significant.
RESULTS
A total of 44,156 patients diagnosed during the study period were selected from our information system: 29,737 were registered in the Hospital Virgen de la Victoria (HVV) and 14,419 in the Hospital Regional. Patient registration at the Hospital Universitario Virgen de la Victoria was initiated in the 1980s, whereas at the Hospital Regional Universitario, it began in 2014. This circumstance could constitute a selection bias, and consequently, the patient population of Hospital Regional could be considered nonrepresentative of the cancer incidence in its population area between 1998 and 2021. Therefore, we decided to include only the population diagnosed at HVV. Of the 29,737 patients selected, 29,514 were age 20 years or older at the time of diagnosis, and in 25,336 cases, the organ involved corresponded to one of the 18 neoplasms included in the study. In 24,596 patients, the neoplasm was diagnosed at the invasive stage and constituted the final study population. There was sufficient information to perform annual incidence change analysis for all patients (Fig 1).
FIG 1.
Flowchart of the study population. HR, Hospital Regional; HVV, Hospital Virgen de la Victoria.
A total of 5,466 (22.2%) patients were age between 20 and 49 years (EOC population), and 19,130 (77.8%) patients were age 50 years and older (LOC population; Table 1). The median age was 42 years in the EOC group and 66 years in the LOC group. Just over 67% of patients younger than 50 years were female, and 51.7% were in the LOC population. The three most common neoplasms in EOC patients were breast (40.5%), non-Hodgkin lymphoma (7.1%), and testicular (6.3%) tumors, and in LOC patients were breast (24.3%), lung (18.7%), and colon (13.6%) tumors.
TABLE 1.
Characteristics of EOC (<50 years) and LOC (≥50 years) Cohorts
| Characteristic | EOC | LOC | Total | P |
|---|---|---|---|---|
| Total, No. (%) | 5,466 (22.2) | 19,130 (77.8) | 24,596 | |
| Age, years, median (range) | 42 (20-49) | 66 (50-98) | ||
| Sex, No. (%) | <.001 | |||
| Male | 1,800 (32.9) | 9,245 (48.3) | 11,045 | |
| Female | 3,666 (67.1) | 9,885 (51.7) | 13,551 | |
| Neoplasms, No. (%) | <.001 | |||
| Head and neck | 244 (4.5) | 1,355 (7.1) | 1,599 | |
| Cervical | 190 (3.5) | 240 (1.3) | 430 | |
| Colon | 300 (5.5) | 2,604 (13.6) | 2,904 | |
| Uterine corpus | 29 (1.6) | 423 (2.2) | 452 | |
| Esophagus | 31 (0.6) | 318 (1.7) | 349 | |
| Stomach | 111 (2.0) | 652 (3.4) | 763 | |
| Testicular | 344 (6.3) | 27 (0.1) | 371 | |
| Hodgkin lymphoma | 253 (4.6) | 94 (0.5) | 347 | |
| Non-Hodgkin lymphoma | 387 (7.1) | 1,187 (6.2) | 1,574 | |
| Breast | 2,213 (40.5) | 4,642 (24.3) | 6,855 | |
| Melanoma | 212 (3.9) | 406 (2.1) | 618 | |
| Ovary | 187 (3.4) | 506 (2.3) | 693 | |
| Pancreas | 77 (1.4) | 545 (2.8) | 622 | |
| Lung | 308 (5.6) | 3,579 (18.7) | 3,887 | |
| Rectum | 203 (3.7) | 1,456 (7.6) | 1,659 | |
| Kidney | 65 (1.2) | 359 (1.9) | 424 | |
| Sarcoma | 294 (5.4) | 475 (2.5) | 769 | |
| Gallbladder and biliary tree | 18 (0.3) | 262 (1.4) | 280 |
Abbreviations: EOC, early-onset cancer; LOC, late-onset cancer.
When analyzing the changes in the annual incidence of different neoplasms (Tables 2 and 3), we observed that the incidence of all tumors increased throughout the study period in both age groups. However, the average annual percentage increase in patients younger than 50 years was higher than that in patients with LOC for the following neoplasms: head and neck (6.1% v 4.6%), colon (11.0% v 8.2%), testicular (16.3% v –13.1%), non-Hodgkin lymphoma (8.4% v 5.9%), rectum (16.1% v 6.8%), kidney (27.8% v 20.1%), and sarcoma (43.4% v 28.6%).
TABLE 2.
AAPC by Age Cohorts (<50 years v ≥50 years)
| Neoplasm | AAPC EOC, % | CI Lower, % | CI Upper, % | AAPC LOC, % | CI Lower, % | CI Upper, % |
|---|---|---|---|---|---|---|
| Total | 2.4 | 2.0 | 2.8 | 5.3 | 5.0 | 5.6 |
| Head and neck | 6.1 | 5.5 | 6.7 | 4.6 | 4.3 | 4.9 |
| Cervical | 28.1 | 26.9 | 29.3 | 35.9 | 35.2 | 36.6 |
| Colon | 11.0 | 10.2 | 11.8 | 8.2 | 7.8 | 8.6 |
| Uterine corpus | 8.3 | 7.6 | 9.0 | 22.1 | 21.5 | 22.7 |
| Esophagus | –29.6 | –28.4 | –30.8 | 25.5 | 24.9 | 26.1 |
| Stomach | 18.4 | 17.4 | 19.4 | 31.1 | 30.4 | 31.8 |
| Testicular | 16.3 | 15.3 | 17.3 | –13.1 | –12.6 | –13.6 |
| Hodgkin lymphoma | 12.1 | 11.2 | 13.0 | 49.0 | 48.3 | 49.7 |
| Non-Hodgkin lymphoma | 8.4 | 7.7 | 9.1 | 5.9 | 5.6 | 6.2 |
| Breast | 2.7 | 2.3 | 3.1 | 6.1 | 5.8 | 6.4 |
| Melanoma | 13.0 | 12.1 | 13.9 | 17.7 | 17.2 | 18.2 |
| Ovary | 11.6 | 10.8 | 12.4 | 14.7 | 14.2 | 15.2 |
| Pancreas | 26.7 | 25.5 | 27.9 | 39.2 | 38.5 | 39.9 |
| Lung | 3.8 | 3.3 | 4.3 | 7.2 | 6.8 | 7.6 |
| Rectum | 16.1 | 15.1 | 17.1 | 6.8 | 6.4 | 7.2 |
| Kidney | 27.8 | 26.6 | 29.0 | 20.1 | 19.5 | 20.7 |
| Sarcomas | 43.4 | 42.1 | 44.7 | 28.6 | 28.0 | 29.2 |
| Gallbladder and biliary tree | –34.9 | –33.6 | –36.2 | 28.7 | 28.1 | 29.3 |
Abbreviations: AAPC EOC, average annual percentage change early-onset cancer; AAPC LOC, average annual percentage change late-onset cancer; CI lower, lower limit of 95% CI; CI upper, upper limit of 95% CI.
TABLE 3.
Summary of Neoplasms With Higher AAPC EOC Than AAPC LOC
| Neoplasm | <50 Years v ≥50 Years, % | <45 Years v ≥45 Years, % | <40 Years v ≥40 Years, % | |||
|---|---|---|---|---|---|---|
| AAPC EOC | AAPC LOC | AAPC EOC | AAPC LOC | AAPC EOC | AAPC LOC | |
| Head and neck | 6.1 | 4.6 | 12.4 | 3.9 | 28.8 | 3.6 |
| Colon | 11.0 | 8.2 | 10.2 | 8.3 | 38.7 | 8.0 |
| Testicular | 16.3 | 13.1 | 16.8 | 3.3 | — | — |
| Non-Hodgkin lymphoma | 8.4 | 5.9 | 17.6 | 5.2 | 22.8 | 5.2 |
| Melanoma | — | — | — | — | 14.5 | 11.7 |
| Ovary | — | — | 24.9 | 6.3 | 34.9 | 4.2 |
| Rectum | 16.1 | 6.8 | 12.2 | 6.9 | — | — |
| Kidney | 27.8 | 20.1 | — | — | — | — |
| Sarcomas | 43.4 | 28.6 | 36.7 | 29.9 | 48.5 | 19.7 |
Abbreviations: AAPC EOC, average annual percentage change early-onset cancer; AAPC LOC, average annual percentage change late-onset cancer.
Analysis of the extent of disease at diagnosis between the two age groups showed no significant differences in most neoplasms. A significantly higher number of early stages was only observed in younger patients with non-Hodgkin lymphoma, testicular, melanoma, and ovarian tumors and in those with more advanced stages of breast tumors (Table 4).
TABLE 4.
Stage at Diagnosis by Age Cohorts (<50 years v ≥50 years)
| Neoplasm Stage | EOC, No. (%) | LOC, No. (%) | Total, No. | P |
|---|---|---|---|---|
| Head and neck | .06 | |||
| I | 24 (10.9) | 181 (14.3) | 205 | |
| II | 37 (16.8) | 149 (11.8) | 186 | |
| III | 49 (22.3) | 351 (27.8) | 400 | |
| IV | 110 (50.0) | 581 (46.0) | 691 | |
| Cervix | .17 | |||
| I | 43 (23.9) | 39 (17.2) | 82 | |
| II | 70 (38.9) | 91 (40.1) | 161 | |
| III | 44 (24.4) | 53 (23.3) | 97 | |
| IV | 23 (12.8) | 44 (19.4) | 67 | |
| Colon | .55 | |||
| I | 16 (5.6) | 104 (4.2) | 120 | |
| II | 78 (27.3) | 665 (26.2) | 743 | |
| III | 97 (33.9) | 928 (37.1) | 1.025 | |
| IV | 95 (33.2) | 806 (32.2) | 901 | |
| Uterine corpus | .46 | |||
| I | 14 (58.3) | 206 (50.9) | 220 | |
| II | 4 (16.7) | 39 (9.6) | 43 | |
| III | 4 (16.7) | 103 (25.4) | 107 | |
| IV | 2 (8.3) | 57 (14.1) | 59 | |
| Esophagus | .92 | |||
| I | — | 9 (35.3) | 9 | |
| II | 6 (23.1) | 54 (21.1) | 60 | |
| III | 10 (38.5) | 88 (34.4) | 98 | |
| IV | 10 (38.5) | 105 (41.0) | 115 | |
| Stomach | .19 | |||
| I | 6 (6.3) | 72 (13.1) | 78 | |
| II | 12 (12.6) | 86 (15.7) | 98 | |
| III | 25 (26.3) | 133 (24.2) | 158 | |
| IV | 52 (54.7) | 258 (47.0) | 310 | |
| Testicular | .001 | |||
| I | 212 (71.6) | 15 (57.7) | 227 | |
| II | 42 (14.2) | 1 (3.8) | 43 | |
| III | 22 (7.4) | 2 (7.7) | 24 | |
| IV | 20 (6.8) | 8 (30.8) | 28 | |
| Hodgkin lymphoma | .12 | |||
| I | 28 (12.4) | 14 (17.7) | 42 | |
| II | 121 (53.5) | 30 (38.0) | 151 | |
| III | 37 (16.4) | 17 (21.5) | 54 | |
| IV | 40 (17.7) | 18 (22.8) | 58 | |
| Non-Hodgkin lymphoma | <.001 | |||
| I | 93 (26.9) | 178 (17.3) | 271 | |
| II | 74 (21.4) | 187 (18.1) | 261 | |
| III | 68 (19.7) | 240 (23.3) | 308 | |
| IV | 111 (32.1) | 426 (41.3) | 537 | |
| Breast | <.001 | |||
| I | 654 (30.2) | 1.729 (38.1) | 2.383 | |
| II | 993 (45.9) | 1.866 (41.1) | 2.859 | |
| III | 380 (17.6) | 676 (14.9) | 1.056 | |
| IV | 135 (6.2) | 271 (6.0) | 406 | |
| Melanoma | .003 | |||
| I | 46 (24.2) | 50 (14.2) | 96 | |
| II | 42 (22.1) | 79 (22.5) | 121 | |
| III | 63 (33.2) | 107 (30.5) | 170 | |
| IV | 39 (20.5) | 115 (32.8) | 154 | |
| Ovary | <.001 | |||
| I | 66 (37.9) | 69 (14.5) | 135 | |
| II | 22 (12.6) | 36 (7.6) | 58 | |
| III | 64 (36.8) | 220 (46.2) | 284 | |
| IV | 22 (12.6) | 151 (31.7) | 173 | |
| Pancreas | .89 | |||
| I | 7 (10.6) | 39 (8.1) | 46 | |
| II | 7 (10.6) | 60 (12.5) | 67 | |
| III | 11 (16.7) | 79 (16.5) | 90 | |
| IV | 41 (62.1) | 301 (62.8) | 342 | |
| Lung | .16 | |||
| I | 12 (4.3) | 227 (7.0) | 239 | |
| II | 13 (4.7) | 183 (5.6) | 196 | |
| III | 75 (27.2) | 965 (29.6) | 1.040 | |
| IV | 176 (63.8) | 1.881 (57.8) | 2.057 | |
| Rectum | .56 | |||
| I | 10 (5.4) | 65 (4.7) | 75 | |
| II | 35 (19.0) | 321 (23.4) | 356 | |
| III | 93 (50.5) | 641 (46.8) | 734 | |
| IV | 46 (25.0) | 343 (25.0) | 389 | |
| Kidney | .1 | |||
| I | 10 (16.9) | 51 (15.8) | 61 | |
| II | 9 (15.3) | 24 (7.5) | 33 | |
| III | 4 (6.8) | 49 (15.2) | 53 | |
| IV | 36 (61.0) | 198 (61.5) | 234 | |
| Sarcomas | .28 | |||
| I | 68 (33.0) | 98 (27.6) | 166 | |
| II | 39 (18.9) | 57 (16.1) | 96 | |
| III | 47 (22.8) | 90 (25.4) | 137 | |
| IV | 52 (25.2) | 110 (31.0) | 162 | |
| Gallbladder and biliary tree | .84 | |||
| I | 1 (5.6) | 24 (11.2) | 25 | |
| II | 2 (11.1) | 31 (14.5) | 33 | |
| III | 5 (27.8) | 31 (14.5) | 36 | |
| IV | 10 (55.6) | 128 (59.8) | 138 |
Abbreviations: EOC, early-onset cancer; LOC, late-onset cancer.
The number of patients younger than 45 years was 3,404 (13.8%) and the number of patients age 45 years and older was 21,192 (86.2%; Table 5). The median age was 39 and 64 years in the former and LOC groups, respectively. Approximately 68% of the patients younger than 45 years were female compared with 53.2% of the patients age 45 years and older. Similar to the analysis performed with an age cutoff of 50 years, the most common neoplasms in younger patients were breast, testicular, and non-Hodgkin lymphoma (38.6%, 8.8%, and 7.5%, respectively). As expected, breast (25.9%), lung (17.9%), and colon (13.1%) neoplasms were the most common neoplasms in the LOC population.
TABLE 5.
Characteristics of EOC (<45 years) and LOC (≥45 years) Cohorts
| Characteristic | EOC | LOC | Total | P |
|---|---|---|---|---|
| Total, No. (%) | 3,404 (13.8) | 21,192 (86.2) | 24,596 | |
| Age, years, median (range) | 39 (20-44) | 64 (45-98) | ||
| Sex, No. (%) | <.001 | |||
| Male | 1,297 (34.3) | 9,748 (46.8) | 11,045 | |
| Female | 2,482 (65.7) | 11,069 (53.2) | 13,551 | |
| Neoplasms, No. (%) | <.001 | |||
| Head and neck | 131 (3.5) | 1,468 (7.1) | 1,599 | |
| Cervical | 147 (3.9) | 283 (1.4) | 430 | |
| Colon | 185 (4.9) | 2,719 (13.1) | 2,904 | |
| Uterine corpus | 16 (0.4) | 436 (2.1) | 452 | |
| Esophagus | 20 (0.5) | 329 (1.6) | 349 | |
| Stomach | 73 (1.9) | 690 (3.3) | 763 | |
| Testicular | 334 (8.8) | 37 (0.2) | 371 | |
| Hodgkin lymphoma | 235 (6.5) | 112 (0.5) | 347 | |
| Non-Hodgkin lymphoma | 285 (7.5) | 1,289 (6.2) | 1,574 | |
| Breast | 1,459 (38.6) | 5,396 (25.9) | 6,855 | |
| Melanoma | 163 (4.3) | 455 (2.2) | 618 | |
| Ovary | 125 (3.3) | 568 (2.7) | 693 | |
| Pancreas | 45 (1.2) | 577 (2.8) | 622 | |
| Lung | 164 (4.3) | 3,723 (17.9) | 3,887 | |
| Rectum | 118 (3.1) | 1,541 (7.4) | 1,659 | |
| Kidney | 39 (1.0) | 385 (1.8) | 424 | |
| Sarcoma | 232 (6.1) | 537 (2.6) | 769 | |
| Gallbladder and biliary tree | 8 (0.2) | 272 (1.3) | 280 |
Abbreviations: EOC, early-onset cancer; LOC, late-onset cancer.
The study of changes in the annual incidence of different neoplasms in these age groups confirmed the results obtained in the previous analysis (Tables 3 and 6). In addition, other types of neoplasms showed a higher AAPC in patients younger than 45 years than in the LOC group: cervical (37.4% v 32.8%), melanoma (22.3% v 14.6%), ovarian (24.9% v 6.3%), and pancreatic (33.1% v 23.2%).
TABLE 6.
AAPC by Age Cohorts (<45 years v ≥45 years)
| Neoplasm | AAPC EOC, % | CI Lower, % | CI Upper, % | AAPC LOC, % | CI Lower, % | CI Upper, % |
|---|---|---|---|---|---|---|
| Total | 2.5 | 2.0 | 3.0 | 5.0 | 4.7 | 5.3 |
| Head and neck | 12.4 | 11.3 | 13.5 | 3.9 | 3.6 | 4.2 |
| Cervical | 37.4 | 35.8 | 39.0 | 32.8 | 32.2 | 33.4 |
| Colon | 10.2 | 9.2 | 11.2 | 8.3 | 7.9 | 8.7 |
| Uterine corpus | –2.1 | –1.6 | –2.6 | 22.1 | 21.5 | 22.7 |
| Esophagus | –29.2 | –27.7 | –30.7 | 23.6 | 23.0 | 24.2 |
| Stomach | 28.8 | 27.3 | 30.3 | 33.1 | 32.5 | 33.7 |
| Testicular | 16.8 | 15.5 | 18.1 | 3.3 | 3.1 | 3.5 |
| Hodgkin lymphoma | 12.0 | 10.9 | 13.1 | 37.8 | 37.1 | 38.5 |
| Non-Hodgkin lymphoma | 17.6 | 16.3 | 18.9 | 5.2 | 4.9 | 5.5 |
| Breast | 2.7 | 2.2 | 3.2 | 5.4 | 5.1 | 5.7 |
| Melanoma | 22.3 | 20.9 | 23.7 | 14.6 | 14.1 | 15.1 |
| Ovary | 24.9 | 23.4 | 26.4 | 6.3 | 6.0 | 6.6 |
| Pancreas | 33.1 | 31.5 | 34.7 | 23.2 | 22.6 | 23.8 |
| Lung | 7.4 | 6.5 | 8.3 | 6.7 | 6.4 | 7.0 |
| Rectum | 12.2 | 11.1 | 13.3 | 6.9 | 6.6 | 7.2 |
| Kidney | –1.7 | –1.3 | –2.1 | 20.3 | 19.8 | 20.8 |
| Sarcomas | 36.7 | 35.1 | 38.3 | 29.9 | 29.3 | 30.5 |
| Gallbladder and biliary tree | –23.8 | –22.4 | –25.2 | 32.0 | 31.4 | 32.6 |
Abbreviations: AAPC EOC, average annual percentage change early-onset cancer; AAPC LOC, average annual percentage change late-onset cancer; CI lower, lower limit of 95% CI; CI upper, upper limit of 95% CI.
The analysis of the possible differences in stage at diagnosis showed results consistent with those observed in previous age groups (Table 7).
TABLE 7.
Stage at Diagnosis by Age Cohorts (<45 years v ≥45 years)
| Neoplasm Stage | EOC, No. (%) | LOC, No. (%) | Total, No. | P |
|---|---|---|---|---|
| Head and neck | .17 | |||
| I | 16 (14.0) | 189 (13.8) | 205 | |
| II | 21 (18.4) | 165 (12.1) | 186 | |
| III | 24 (21.1) | 376 (27.5) | 400 | |
| IV | 53 (46.5) | 638 (46.6) | 691 | |
| Cervix | .04 | |||
| I | 33 (24.1) | 49 (18.1) | 82 | |
| II | 57 (41.6) | 104 (38.5) | 161 | |
| III | 34 (24.8) | 63 (23.3) | 97 | |
| IV | 13 (9.5) | 54 (20.0) | 67 | |
| Colon | ||||
| I | 15 (8.7) | 105 (4.0) | 120 | .03 |
| II | 44 (25.4) | 699 (26.7) | 743 | |
| III | 58 (33.5) | 967 (37.0) | 1.025 | |
| IV | 56 (32.4) | 845 (32.3) | 901 | |
| Uterine corpus | .04 | |||
| I | 8 (66.7) | 212 (50.8) | 220 | |
| II | 3 (25.0) | 40 (9.6) | 43 | |
| III | — | 107 (25.7) | 107 | |
| IV | 1 (8.3) | 58 (13.9) | 59 | |
| Esophagus | .96 | |||
| I | — | 9 (3.4) | 9 | |
| II | 4 (25.0) | 56 (21.1) | 60 | |
| III | 5 (31.3) | 93 (35.0) | 98 | |
| IV | 7 (43.8) | 108 (40.6) | 115 | |
| Stomach | .56 | |||
| I | 5 (8.1) | 73 (12.5) | 78 | |
| II | 7 (11.3) | 91 (15.6) | 98 | |
| III | 16 (25.8) | 142 (24.4) | 158 | |
| IV | 34 (54.8) | 276 (47.4) | 310 | |
| Testicular | .005 | |||
| I | 208 (72.5) | 19 (54.3) | 227 | |
| II | 39 (13.6) | 4 (11.4) | 43 | |
| III | 21 (7.3) | 3 (8.6) | 24 | |
| IV | 19 (6.6) | 9 (25.7) | 28 | |
| Hodgkin lymphoma | .1 | |||
| I | 28 (13.1) | 14 (15.2) | 42 | |
| II | 115 (54.0) | 36 (39.1) | 151 | |
| III | 35 (16.4) | 19 (20.7) | 54 | |
| IV | 35 (16.4) | 23 (25.0) | 58 | |
| Non-Hodgkin lymphoma | <.001 | |||
| I | 75 (29.6) | 196 (17.4) | 271 | |
| II | 50 (19.8) | 211 (18.8) | 261 | |
| III | 48 (19.0) | 260 (23.1) | 308 | |
| IV | 80 (31.6) | 457 (40.7) | 537 | |
| Breast | <.001 | |||
| I | 403 (28.4) | 1.980 (37.5) | 2.383 | |
| II | 637 (44.9) | 2.222 (42.1) | 2.859 | |
| III | 280 (19.7) | 776 (14.7) | 1.056 | |
| IV | 100 (7.0) | 306 (5.8) | 406 | |
| Melanoma | .001 | |||
| I | 39 (26.9) | 57 (14.4) | 96 | |
| II | 33 (22.8) | 88 (22.2) | 121 | |
| III | 46 (31.7) | 124 (31.3) | 170 | |
| IV | 27 (18.6) | 127 (32.1) | 154 | |
| Ovary | <.001 | |||
| I | 48 (40.0) | 87 (16.4) | 135 | |
| II | 14 (11.7) | 44 (8.3) | 58 | |
| III | 44 (36.7) | 240 (45.3) | 284 | |
| IV | 14 (11.7) | 159 (30.0) | 173 | |
| Pancreas | .9 | |||
| I | 4 (9.8) | 42 (8.3) | 46 | |
| II | 6 (14.6) | 61 (12.1) | 67 | |
| III | 6 (14.6) | 84 (16.7) | 90 | |
| IV | 25 (61.0) | 317 (62.9) | 342 | |
| Lung | 0 | .1 | ||
| I | 6 (4.1) | 233 (6.9) | 239 | |
| II | 8 (5.4) | 188 (5.6) | 196 | |
| III | 34 (23.0) | 1.006 (29.7) | 1.040 | |
| IV | 100 (67.6) | 1.957 (57.8) | 2.057 | |
| Rectum | .622 | |||
| I | 7 (6.6) | 68 (4.7) | 75 | |
| II | 24 (22.6) | 332 (22.9) | 356 | |
| III | 53 (50.0) | 681 (47.0) | 734 | |
| IV | 22 (20.8) | 367 (25.3) | 389 | |
| Kidney | .44 | |||
| I | 6 (16.7) | 55 (16.9) | 61 | |
| II | 4 (11.1) | 29 (8.4) | 33 | |
| III | 2 (5.6) | 51 (14.8) | 53 | |
| IV | 24 (66.7) | 210 (60.9) | 234 | |
| Sarcomas | .76 | |||
| I | 49 (30.8) | 117 (29.1) | 166 | |
| II | 29 (18.2) | 67 (16.7) | 96 | |
| III | 34 (21.4) | 103 (25.6) | 137 | |
| IV | 47 (29.6) | 115 (28.6) | 162 | |
| Gallbladder and biliary tree | .93 | |||
| I | — | 25 (11.2) | 25 | |
| II | 1 (14.3) | 32 (14.3) | 33 | |
| III | — | 35 (15.6) | 35 | |
| IV | 6 (85.7) | 132 (58.9) | 138 |
Abbreviations: EOC, early-onset cancer; LOC, late-onset cancer.
The study of the youngest age group showed that only 7.8% (n = 1,920) of our study population was younger than 40 years (Table 8), with a median age of 34 years and almost 60% females. The most common neoplasms in both groups were the same as in the two previous analyses, with the only difference being that in patients younger than 40 years, the most common lymphoma was Hodgkin lymphoma instead of non-Hodgkin lymphoma.
TABLE 8.
Characteristics of EOC (<40 years) and LOC (≥40 years) Cohorts
| Characteristic | EOC | LOC | Total | P |
|---|---|---|---|---|
| Total, No. (%) | 1,920 (7.8) | 22,676 (92.2) | 24,596 | |
| Age, years, median (range) | 34 (20-39) | 63 (40-98) | ||
| Sex, No. (%) | <.001 | |||
| Male | 771 (40.2) | 10,274 (45.3) | 11,045 | |
| Female | 1,149 (59.8) | 12,402 (54.7) | 13,551 | |
| Neoplasms, No. (%) | <.001 | |||
| Head and neck | 56 (2.9) | 1,543 (6.8) | 1,599 | |
| Cervical | 70 (3.6) | 360 (1.6) | 430 | |
| Colon | 75 (3.9) | 2,829 (12.5) | 2,904 | |
| Uterine corpus | 6 (0.3) | 446 (2.0) | 452 | |
| Esophagus | 9 (0.5) | 340 (1.5) | 349 | |
| Stomach | 28 (1.2) | 735 (3.2) | 763 | |
| Testicular | 277 (14.4) | 94 (0.4) | 371 | |
| Hodgkin lymphoma | 195 (10.2) | 152 (0.7) | 347 | |
| Non-Hodgkin lymphoma | 172 (9.0) | 1,402 (6.2) | 1,574 | |
| Breast | 571 (29.7) | 6,284 (27.7) | 6,855 | |
| Melanoma | 106 (5.5) | 512 (2.3) | 618 | |
| Ovary | 62 (3.2) | 631 (2.8) | 693 | |
| Pancreas | 12 (0.6) | 610 (2.7) | 622 | |
| Lung | 51 (2.7) | 3,836 (16.9) | 3,887 | |
| Rectum | 46 (2.4) | 1,613 (7.1) | 1,659 | |
| Kidney | 20 (1.0) | 404 (1.8) | 424 | |
| Sarcoma | 162 (8.4) | 607 (2.7) | 769 | |
| Gallbladder and biliary tree | 2 (0.1) | 278 (1.2) | 280 |
Abbreviations: EOC, early-onset cancer; LOC, late-onset cancer.
In these age groups, several neoplasms showed a higher increase in average annual percentage (Tables 3 and 9): head and neck (28.8% v 4.8%), colon (38.7% v 8.0%), non-Hodgkin lymphoma (22.8% v 5.2%), melanoma (14.5% v 11.7%), ovarian (34.9% v 4.2%), and sarcoma (48.5% v 19.7%).
TABLE 9.
AAPC by Age Cohorts (<40 years v ≥40 years)
| Neoplasm | AAPC EOC, % | CI Lower, % | CI Upper, % | AAPC LOC, % | CI Lower, % | CI Upper, % |
|---|---|---|---|---|---|---|
| Total | 2.7 | 2.0 | 3.4 | 4.8 | 4.5 | 5.1 |
| Head and neck | 28.8 | 26.8 | 30.8 | 3.6 | 3.4 | 3.8 |
| Cervical | 6.9 | 5.8 | 8.0 | 23.0 | 22.5 | 23.5 |
| Colon | 38.7 | 36.5 | 40.9 | 8.0 | 7.6 | 8.4 |
| Uterine corpus | –8.3 | –7.1 | –9.5 | 22.5 | 22.0 | 23.0 |
| Esophagus | –27.1 | 25.1 | –29.1 | 22.2 | 21.7 | 22.7 |
| Stomach | –19.4 | 17.6 | –21.2 | 35.5 | 34.9 | 36.1 |
| Testicular | 17.3 | 15.6 | 19.0 | 43.3 | 42.7 | 43.9 |
| Hodgkin lymphoma | 12.0 | 10.5 | 13.5 | 37.8 | 37.2 | 38.4 |
| Non-Hodgkin lymphoma | 22.8 | 20.9 | 24.7 | 5.2 | 4.9 | 5.5 |
| Breast | 2.5 | 1.8 | 3.2 | 5.1 | 4.8 | 5.4 |
| Melanoma | 14.5 | 12.9 | 16.1 | 11.7 | 11.3 | 12.1 |
| Ovary | 34.9 | 32.8 | 37.0 | 4.2 | 3.9 | 4.5 |
| Pancreas | –17.4 | –15.7 | –19.1 | 25.0 | 24.4 | 25.6 |
| Lung | –1.0 | –0.6 | –1.4 | 6.2 | 5.9 | 6.5 |
| Rectum | –19.4 | –17.6 | –21.2 | 6.4 | 6.1 | 6.7 |
| Kidney | –30.6 | –28.5 | –32.7 | 21.8 | 21.3 | 22.3 |
| Sarcomas | 48.5 | 46.3 | 50.7 | 19.7 | 19.2 | 20.2 |
| Gallbladder and biliary tree | –9.5 | –8.2 | –10.8 | 31.5 | 30.9 | 32.1 |
Abbreviations: AAPC EOC, average annual percentage change early-onset cancer; AAPC LOC, average annual percentage change late-onset cancer; CI lower, lower limit of 95% CI; CI upper, upper limit of 95% CI.
Data regarding the extent of the disease at diagnosis were similar to those reported in previous studies. A significantly higher number of early stages was observed only in younger patients with colon, non-Hodgkin lymphoma, testicular, melanoma, ovarian, and more advanced stages in breast tumors (Table 10).
TABLE 10.
Stage at Diagnosis by Age Cohorts (<40 years v ≥40 years)
| Neoplasm Stage | EOC, No. (%) | LOC, No. (%) | Total, No. | P |
|---|---|---|---|---|
| Head and neck | .15 | |||
| I | 9 (18.0) | 196 (13.7) | 205 | |
| II | 9 (18.0) | 177 (12.4) | 186 | |
| III | 7 (14.0) | 393 (27.4) | 400 | |
| IV | 25 (50.0) | 666 (46.5) | 691 | |
| Cervix | .06 | |||
| I | 18 (28.6) | 64 (18.6) | 82 | |
| II | 22 (34.9) | 139 (40.4) | 161 | |
| III | 18 (28.6) | 79 (23.0) | 97 | |
| IV | 5 (7.9) | 62 (18.0) | 67 | |
| Colon | <.001 | |||
| I | 10 (14.7) | 110 (4.0) | 120 | |
| II | 20 (29.4) | 723 (26.6) | 743 | |
| III | 17 (25.0) | 1.008 (37.0) | 1.025 | |
| IV | 21 (30.9) | 880 (32.3) | 901 | |
| Uterine corpus | .093 | |||
| I | 2 (40.0) | 218 (51.4) | 220 | |
| II | 2 (40.0) | 41 (9.7) | 43 | |
| III | — | 107 (25.2) | 107 | |
| IV | 1 (20.0) | 58 (13.7) | 59 | |
| Esophagus | .63 | |||
| I | — | 9 (3.3) | 9 | |
| II | 2 (28.6) | 58 (21.1) | 60 | |
| III | 1 (14.3) | 97 (35.3) | 98 | |
| IV | 4 (57.1) | 111 (40.4) | 115 | |
| Stomach | .23 | |||
| I | 2 (8.7) | 76 (12.2) | 78 | |
| II | 4 (17.4) | 94 (15.1) | 98 | |
| III | 2 (8.7) | 156 (25.1) | 158 | |
| IV | 15 (65.1) | 295 (47.5) | 310 | |
| Testicular | ||||
| I | 168 (70.6) | 59 (70.2) | 227 | .046 |
| II | 36 (15.1) | 7 (8.3) | 43 | |
| III | 19 (8.0) | 5 (6.0) | 24 | |
| IV | 15 (6.3) | 13 (15.5) | 28 | |
| Hodgkin lymphoma | .038 | |||
| I | 20 (11.3) | 22 (17.2) | 42 | |
| II | 100 (56.5) | 51 (39.8) | 151 | |
| III | 28 (15.8) | 26 (20.3) | 54 | |
| IV | 29 (16.4) | 29 (22.7) | 58 | |
| Non-Hodgkin lymphoma | <.001 | |||
| I | 50 (32.3) | 221 (18.1) | 271 | |
| II | 31 (20.0) | 230 (18.8) | 261 | |
| III | 30 (19.4) | 278 (22.7) | 308 | |
| IV | 44 (28.4) | 493 (40.3) | 537 | |
| Breast | <.001 | |||
| I | 135 (24.3) | 2.248 (36.6) | 2.383 | |
| II | 241 (43.4) | 2.618 (45.6) | 2.859 | |
| III | 132 (23.8) | 924 (15.0) | 1.056 | |
| IV | 47 (8.5) | 359 (5.8) | 406 | |
| Melanoma | <.001 | |||
| I | 30 (31.9) | 66 (14.8) | 96 | |
| II | 19 (20.2) | 102 (22.8) | 121 | |
| III | 30 (31.9) | 140 (31.3) | 170 | |
| IV | 15 (16.0) | 139 (31.1) | 154 | |
| Ovary | <.001 | |||
| I | 28 (46.7) | 107 (18.1) | 135 | |
| II | 10 (16.7) | 48 (8.1) | 58 | |
| III | 18 (30.0) | 266 (45.1) | 284 | |
| IV | 4 (6.7) | 169 (28.6) | 173 | |
| Pancreas | .624 | |||
| I | — | 46 (8.6) | 46 | |
| II | 1 (10.0) | 66 (12.6) | 67 | |
| III | 3 (30.0) | 87 (65.8) | 90 | |
| IV | 6 (60.0) | 336 | 342 | |
| Lung | .933 | |||
| I | 3 (6.7) | 236 (6.8) | 239 | |
| II | 3 (6.7) | 193 (5.5) | 196 | |
| III | 12 (26.7) | 1.028 (29.5) | 1.040 | |
| IV | 27 (60.0) | 2.030 (58.2) | 2.057 | |
| Rectum | .452 | |||
| I | 4 (10.0) | 71 (4.7) | 75 | |
| II | 8 (20) | 348 (23.0) | 356 | |
| III | 19 (47.5) | 715 (47.2) | 734 | |
| IV | 9 (22.5) | 380 (25.1) | 389 | |
| Kidney | .824 | |||
| I | 3 (16.7) | 58 (16.0) | 61 | |
| II | 1 (5.6) | 32 (8.8) | 33 | |
| III | 1 (5.6) | 52 (14.3) | 53 | |
| IV | 13 (72.2) | 221 (60.9) | 234 | |
| Sarcomas | .654 | |||
| I | 36 (31.9) | 130 (29.0) | 166 | |
| II | 17 (15.0) | 79 (17.6) | 96 | |
| III | 24 (21.2) | 113 (25.2) | 137 | |
| IV | 36 (31.9) | 126 (28.1) | 162 | |
| Gallbladder and biliary tree | .163 | |||
| I | — | 25 (10.9) | 25 | |
| II | 1 (50.0) | 32 (13.9) | 33 | |
| III | 1 (50.0) | 35 (15.2) | 36 | |
| IV | — | 138 (60.0) | 138 |
Abbreviations: EOC, early-onset cancer; LOC, late-onset cancer.
DISCUSSION
The increase in cancer cases in patients younger than 50 years is undoubtedly a global public health problem. Several studies, primarily based on population-based cancer registry data, have reported a significant increase in the incidence of various tumor types in individuals born between the 1970s and the 1990s in virtually all countries worldwide. More critically, this increase in incidence was greater than that observed in individuals born in the 1950s.2,19 This increase in incidence has been observed in several types of neoplasms, especially in those related to obesity: colorectal,2,4-7,12,13,19,20 uterine corpus,2,13 gallbladder,2 kidney,2,12,13 pancreas,2,9,13 breast,13,21 esophageal adenocarcinoma,2,10 gastric,2,13,22 and multiple myeloma.2 The number of cases diagnosed in successive generations has also been observed to increase in neoplasms unrelated to obesity, such as gastric noncardia, cutaneous melanoma, and oropharyngeal-related or testicular tumors. However, in other tumor sites, the incidence has decreased (cervical, squamous cell esophagus, bladder, lung, larynx, and non-Hodgkin lymphoma) or remains stable (brain and Hodgkin lymphoma).2,12,13 There has also been an increase in the global incidence of neoplasms in young adults (age between 20 and 39 years), not only in those typical of this age group but also in some of the neoplasms associated with obesity: thyroid,23,24 colorectal,23,24 breast,21,23,24 kidney,23 uterine corpus,23 gallbladder,23 liver,23 gastric,8,22 and pancreatic.9
Our results show that cancer incidence in our reference population has increased over the 24 years of the study in both the EOC and LOC groups. Although this increase was higher in patients age 50 years and older, the differences have favored EOC patients for some neoplasms. The magnitude of the increase in the number of cases was higher in patients younger than 50 years in head and neck tumors, colon, testicular, non-Hodgkin lymphoma, rectum, kidney, and sarcoma. In addition, the analysis performed with a cutoff point of 45 years has confirmed this increase in incidence and highlighted the increase in other types of neoplasms, such as cervical, melanoma, ovarian, and pancreatic. Not all of these increases were observed when examining the differences between <40 and ≥40 years groups, but this fact could be due to the small size of the <40 years population. However, our results do not seem to indicate that cancer cases in young patients are diagnosed at more advanced stages than in patients age 50 years and older. Moreover, significant differences are found in some types of neoplasia, but it favors early stages.
Our results are consistent with data published in the literature for most of the tumor sites analyzed. However, in some cases, the increased incidence observed in our patients younger than 50 years to those age 50 years and older has not been reported in other studies (cervical, ovarian, non-Hodgkin lymphoma, and sarcoma).1,2,12,23 In addition, we did not find data observed in other studies for some sites such as the uterine corpus, esophageal adenocarcinoma, stomach, or gallbladder.1,2,12,23 In this regard, it is important to point out that these studies used data from a population-based cancer registry, whereas our study used data from a clinic-based cohort included in an institutional registry of a single hospital. In addition, information in the supplementary material of the published data shows that there are several countries where the incidence patterns of these neoplasms do not follow the trend of global data, as is the case in our results.1,23
It does not seem likely that the screening procedures may have influenced our results. Of the neoplasms analyzed, only screening for cervical cancer and breast cancer was implemented in our region, and we only observed a greater increase in the incidence of cervical cancer in the group younger than 45 years compared with those age 45 years and older (37.4% v 32.8%).1
Providing data that contribute to understanding changes in cancer incidence is of unquestionable interest, especially in young patients. Although the absolute incidence and mortality rates of cancer are lower in younger patients than in adults,12 the individual, social, and economic impacts are much more significant in patients younger than 50 years. Patients diagnosed with cancer at an early age have disrupted future life plans, further altering their expected contribution to society's economic and demographic maintenance. In addition, the disease and treatments used can leave patients with sequelae that require health systems to provide appropriate resources for their care.3,25
Analysis of the incidence patterns in successive generations can help identify various risk factors that may have contributed to the appearance of these changes and thus implement measures to reduce their impact on future generations. Several epidemiologic studies have shown that the multiple environmental factors to which individuals are exposed during early life and young adulthood have changed significantly since the second half of the 20th century.2,15,26,27 These factors include changes in diet, adoption of a Western-style diet, and an increase in sugar-sweetened beverages.28,29 As a result of these changes, the prevalence of obesity and type 2 diabetes mellitus has increased and, therefore, so have the adverse effects of both pathologies on the future development of possible neoplasms.30,31 All of the above would have been exacerbated by other lifestyle changes related to increased sedentary habits, decreased physical activity, and hours of sleep.32,33 Other factors of unquestionable interest that should also be considered are the effects of indiscriminate use of antibiotics on the microbiota and the subsequent risk of developing some types of neoplasia, mainly colorectal cancer.34,35 Another relevant point in the analysis of the causes that have led to an increase in cancer cases in young patients is the study of the genomic and molecular characteristics of the onset of cancer in both age groups. It appears that tumors in patients with EOC have fewer mutations, but a greater number would be driver mutations. In addition, there may be differences in the tumor immune microenvironment between the two groups of patients.36
Actions at all levels of health, politics, and society are needed to change trends in future generations. These actions should aim to promote a healthy lifestyle in the broadest sense. Additionally, it is essential to act directly on the population of children, adolescents, and young adults with overweight and obesity problems by implementing targeted measures in the family, school, and primary care that will allow them to normalize their weight sustainably. However, further research is needed on the genetic and epidemiologic risk factors that lead to the development of EOC.
The consequences of lowering the age of access to screening programs are still being determined, and further research is needed. A recent study identified four signs and symptoms that would favor early diagnosis of colorectal EOC.37 However, these common symptoms may require an additional screening method before colonoscopy to ensure that the screening process is truly efficient.38 Health care professionals should be aware of certain symptoms and should not ignore them because patients are young.
The main strength of our study is that it used high-quality data collected prospectively and systematically from an impressive number of patients collected at a single center. In addition, the study period was very long, allowing for a detailed analysis of the changes in incidence over time. Furthermore, data on the changes in the incidence of several obesity-related and non–obesity-related neoplasms are presented. The concordant results obtained in the three analyses strengthen our data. Moreover, they show that, at least in our population, there is an increase in the incidence of cancer cases in younger age groups than those usually accepted in the definition of EOC, suggesting that the relevance of the problem could be even greater than currently considered. The origin of the study data could be considered a limitation because they were not collected in a population registry but in a hospital-based registry of cancer incidence in a specific geographical area. However, it is important to note that our study provides local data from a circumscribed area that agrees with a large population of published studies. Nevertheless, we do not have data on the total incidence in this area because part of this population is treated in private care.
In conclusion, our results show once again that there is a greater increase in the incidence of cases of certain types of malignancies in the population born in the last decades of the 20th century than in previous generations. Although this increase has been observed in obesity-related neoplasms, similar changes have been observed in other types of neoplasms, suggesting that factors other than lifestyle changes may be involved. This problem is of enormous importance now and in the future, so maximum effort should be devoted to its study and management.
AUTHOR CONTRIBUTIONS
Conception and design: Nuria Ribelles, Emilio Alba
Administrative support: Nuria Ribelles
Provision of study materials or patients: All authors
Collection and assembly of data: All authors
Data analysis and interpretation: Nuria Ribelles, Javier Pascual, Javier Garcia-Corbacho, Emilio Alba
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Nuria Ribelles
Speakers' Bureau: Novartis, Pfizer, Gilead Sciences, Daiichi Sankyo/Astra Zeneca
Research Funding: Pfizer (Inst)
Javier Pascual
Honoraria: Pfizer, Novartis, AstraZeneca
Consulting or Advisory Role: AstraZeneca
Travel, Accommodations, Expenses: AstraZeneca, Gilead Sciences, Pfizer
Jose Carlos Benitez
Research Funding: AstraZeneca (Inst), Gilead Sciences (Inst)
Travel, Accommodations, Expenses: AstraZeneca Spain, Sanofi, Roche, Takeda, Daiichi Sankyo/Astra Zeneca
Esperanza Torres
Travel, Accommodations, Expenses: Merck
Antonio Rueda
Honoraria: Roche, Bristol Myers Squibb, Merck Serono
Consulting or Advisory Role: Roche, Bristol Myers Squibb, Merck Serono, MSD, Takeda, Novartis
Emilio Alba
Consulting or Advisory Role: Pfizer, Novartis, Roche, Lilly, Bristol Myers Squibb, Exact Sciences
Travel, Accommodations, Expenses: Merck Sharp & Dohme
No other potential conflicts of interest were reported.
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