Abstract
BACKGROUND: It has been suggested that alcohol consumption is associated with increased risk of a few solid cancers, although studies that examined the association with hematological malignancies have shown inconsistent results. In this study, we examined the risk of hematological malignancies among individuals who had alcohol use disorders (AUDs) in Sweden. METHODS: Individuals with AUDs were identified from the nationwide Swedish Hospital Discharge Register and Outpatient Register, the Crime Register, and the Prescription Drug Register, and they were linked to the Swedish Cancer Registry to calculate standardized incidence ratios (SIRs) of hematological malignancies, using those Swedes without AUDs as a reference. In addition, we used a quasi-experimental sibling design to investigate the odds ratios among sibling pairs who were discordant with AUDs. RESULTS: A total of 420,489 individuals were identified with AUDs. After more than 15 million person-years of follow-up, a total of 1755 individuals developed hematological malignancies demonstrating a low risk, i.e., SIR = 0.60 (95% confidence interval = 0.57-0.63). People with AUDs had low risks for developing specific types of malignancies. The lowest risk (0.51) was for leukemia, followed by myeloma (0.52), non-Hodgkin lymphoma (0.65), and Hodgkin disease (0.71). The risk was lower among AUDs identified at an older age. The low risks of hematological malignancies were also noted using sibling analysis. CONCLUSIONS: Our data suggest that alcohol consumption has a protective effect against hematological malignancies. However, further studies are needed to identity the underlying mechanisms of the protective effect of alcohol consumption against hematological malignancies.
Introduction
Alcohol use disorders (AUDs), including alcohol abuse and/or dependence, is a substantial worldwide health problem and a major contributor to the global burden of diseases [1,2]. In Sweden, AUDs affect around 18% of men and 5% of women [3,4]. Many diseases, including depressive episodes, severe anxiety, insomnia, suicide, abuse of other drugs, hypertension, heart disease, stroke, liver cirrhosis, fatal accident, and some types of solid cancers, are potentially related to excessive alcohol use [1,2]. According to the report from the International Agency for Research on Cancer [5,6], a few cancer sites, including the oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast, are believed to be causally related to alcohol consumption. Acetaldehyde derived from the metabolism of ethanol in alcohol contributes to the development of malignant esophageal cancers [5,6], but the mechanism of carcinogenesis to the other cancers is not clear.
Hematological malignancies include a heterogeneous group of malignancies, and their etiology is not fully understood. Studies that examine the associations of alcoholic beverage consumption with the risk for these hematological malignancies are limited compared to studies on the associations with solid cancers [7]. Interestingly, several previous studies found a negative association of alcohol consumption with non-Hodgkin lymphoma [8–12]. However, inconsistent data are reported in many other studies [13–15]. Possible reasons for the observed inconsistencies are different study designs, small numbers of cases, and bias due to reporting of alcohol consumption. Studies examining the associations with Hodgkin lymphoma, myeloma, and leukemia are also limited [7]. In this study, we used the national Swedish Registries including data from a total population to examine the risk of hematological malignancies (Hodgkin and non-Hodgkin lymphomas, myeloma, and leukemia) among a total of 420,489 individuals with AUDs, compared to those without AUDs. In addition, we used the quasi-experimental sibling design, which was believed to provide stronger causal evidence by controlling for unmeasured confounding factors (unmeasured genetic and environmental factors) [16], to confirm our observation by studying the effect of different AUD exposures among siblings on hematological malignancies.
Methods
This study was approved by the Ethics Committee at Lund University (Malmö, Sweden), 2013. Patients diagnosed with AUDs were identified using data from the following: 1) the Swedish Hospital Discharge Register and Outpatient Register for 1987 to 2010 (international classification of diseases-9: 291A-291F, 291W, 291X, 303, and 305A; and ICD-10: F10), 2) the Crime Register for 1973 to 2010 (to identify individuals who committed alcohol-related crimes), and 3) the Prescription Drug Register for 2005 to 2010 (to identify individuals prescribed with disulfiram, naltrexone, or acamprosate, which are usually used to treat AUDs) [17].
The Swedish Hospital Discharge Register contains hospital discharge records for all Swedish residents. Data were initially collected in the 1960s by 26 regional health authorities and were compiled by the National Board of Health and Welfare. From 1987 forward, the register included nationwide data. The National Board of Health and Welfare estimates that it contains information on 99% of all public hospitalizations. Because Sweden has very few providers of private inpatient care, this registry covers the majority of hospital admissions. Each year, 1.5 million records are added to the Hospital Discharge Register. The results of a recent external review suggest that the overall accuracy of diagnoses in this register is about 85% to 95% [18]. The information for each hospitalization comprises dates of admission and discharge, hospital and clinic codes, and up to eight discharge diagnosis codes, the first of which defines the principal cause of hospitalization. Patients were identified as AUDs if any of the eight discharge codes contained the ICD codes listed above. The Swedish Outpatient Register was created in 2001 by the National Board of Health and Welfare. Although data on outpatient care from public hospitals are almost 100% complete, the register contains no data from small private outpatient clinics, meaning that its overall national coverage is around 80%.
The Swedish Crime Register contains complete nationwide data on all convictions, including those for alcohol abuse, from 1973 to 2010. Individuals with alcohol-associated drunk driving were identified as AUDs. The Swedish Prescribed Drug Register has 100% coverage. Information on prescriptions and expenditures for prescribed drugs in the entire Swedish population covers the period July 2005 to December 2010. From the above-listed Swedish Registers, we identified 420,489 unique individuals with a phenotype of AUDs between 1973 and 2010 (lifetime prevalence in Sweden ~ 3.8%). We did a sensitivity analysis to examine the risks of cancers in the esophagus and upper aerodigestive tract (including oral, larynx, and pharynx), which are known to be associated with alcohol consumption, among individuals with AUDs to see whether AUDs identified in this study can represent the general population with excess alcohol consumption (Table W1).
We further linked these individuals with AUDs to the Swedish Cancer Registry to identify all incident cases of hematological malignancies during the study period. Hematological malignancies examined in this study include non-Hodgkin lymphoma (international classification of diseases-7 codes 200, 202, and 2041), Hodgkin disease (201), myeloma (203), and leukemia (204-209, except 2041). We also examined the risks of a few subtype lymphomas. Only those subtypes that were significantly associated with AUDs were presented (diffuse, follicular non-Hodgkin lymphoma and mixed cellularity and nodular sclerosis classic Hodgkin lymphoma). The Swedish Cancer Registry was founded in 1958 by the National Board of Health and Welfare. Since the mid-80s, there are six regional registries associated with the oncological centers in each medical region of Sweden where the registration, coding, major check-up, and correction work are performed with a close to 100% coverage in the whole Sweden. In Sweden, it is compulsory for clinicians and pathologists/cytologists to report all newly diagnosed cancers to the Cancer Registry [19]. Additional linkages were made to the Swedish National Population and Housing Census [20] to obtain information on individual-level characteristics, such as year of birth, sex, place of living, and country of birth, to the Cause of Death Register to identify date of death, and to the Emigration Registry to identify date of emigration. All linkages were performed using individual national identification numbers, which were replaced with serial numbers to preserve anonymity.
Among individuals with AUDs including a total of 420,489, we calculated person-years at risk for the hematological malignancies from the latter from the date of birth, immigration, or 1 January 1961 (when the Death of Cause Registry was started in Sweden) to the earliest of the date of diagnosis of cancer, death, emigration, or the end of the study period (31 December 2010). Standardized incidence ratios (SIRs) were calculated as the ratio of the observed to expected number of cases [21,22]. The expected number of cases was calculated according to the incidence rate for all individuals without AUDs. SIRs were standardized by 5-year age group, sex, 5-year time period, education level (≤ 9, 10-11, and 12 +), and region (big cities, south Sweden, and north Sweden) [23]. The 95% confidence intervals (CIs) were calculated and rounded to two decimal places for SIR, assuming a Poisson distribution [23].
We further selected a subsample of siblings with discordant AUDs exposure to examine the odds ratios (OR) of hematological malignancies. Only those families with at least two siblings and at least one sibling with AUDs were selected. For those families with more than two siblings, those siblings without AUDs but with their birth year close to the sibling with AUDs were selected. In total, we selected 20,084 sibling pairs with discordant AUDs. We used conditional logistic regression to calculate OR, adjusted for year of birth and gender. All analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC).
The study was approved by the Ethics Committee at Lund University.
Results
The basic characteristics of individuals with AUDs in Sweden identified between 1973 and 2010 are presented in Table 1. From a total of 420,489 individuals, three times as many men versus women were identified with AUDs. The median age at identification was 41 years for men and 40 years for women. The prevalence of AUDs was more common among individuals with low education levels and those living in big cities.
Table 1.
Basic Characteristics among Individuals with AUDs in Sweden (1973-2010).
| Male |
Female |
All |
||||
|---|---|---|---|---|---|---|
| No. | % | No. | % | No. | % | |
| Age at identification | ||||||
| < 20 | 30,390 | 9.4 | 16,979 | 17.4 | 47,369 | 11.3 |
| 20-29 | 65,495 | 20.3 | 15,258 | 15.7 | 80,753 | 19.2 |
| 30-39 | 56,729 | 17.6 | 14,989 | 15.4 | 71,718 | 17.1 |
| 40-49 | 65,333 | 20.2 | 20,270 | 20.8 | 85,603 | 20.4 |
| 50-59 | 54,412 | 16.8 | 15,816 | 16.2 | 70,228 | 16.7 |
| 60 + | 50,776 | 15.7 | 14,042 | 14.4 | 64,818 | 15.4 |
| Period | ||||||
| < 1990 | 38,201 | 11.8 | 10,239 | 10.5 | 48,440 | 11.5 |
| 1990-1994 | 90,592 | 28.0 | 16,305 | 16.7 | 106,897 | 25.4 |
| 1995-1989 | 57,215 | 17.7 | 15,059 | 15.5 | 72,274 | 17.2 |
| 2000-2004 | 66,602 | 20.6 | 23,359 | 24.0 | 89,961 | 21.4 |
| 2005 + | 70,525 | 21.8 | 32,392 | 33.3 | 102,917 | 24.5 |
| Education (years) | ||||||
| ≤ 9 | 121,273 | 37.5 | 32,775 | 33.7 | 154,048 | 36.6 |
| 10-11 | 101,464 | 31.4 | 29,328 | 30.1 | 130,792 | 31.1 |
| 12 + | 96,385 | 29.8 | 34,252 | 35.2 | 130,637 | 31.1 |
| Unknown | 4,013 | 1.2 | 999 | 1.0 | 5,012 | 1.2 |
| Region | ||||||
| Big cities | 152,679 | 47.2 | 48,105 | 49.4 | 200,784 | 47.8 |
| South | 106,096 | 32.8 | 29,756 | 30.6 | 135,852 | 32.3 |
| North | 50,469 | 15.6 | 14,453 | 14.8 | 64,922 | 15.4 |
| Unknown | 13,891 | 4.3 | 5,040 | 5.2 | 18,931 | 4.5 |
| All | 323,135 | 100.0 | 97,354 | 100.0 | 420,489 | 100.0 |
The risk of hematological malignancies among the individuals with AUDs is presented in Table 2, which was standardized by age, sex, time period, education level, and region. After more than 15 million person-years of follow-up, a total of 1755 individuals were diagnosed with hematological malignancies. The overall risk was 40% lower than in the general population without AUDs (SIR = 0.60, 95% CI = 0.57-0.63). For specific types of malignancies, most of them exhibited SIRs lower than 1.0 with the exception of nodular sclerosis classic Hodgkin lymphoma in men and mixed cellularity classic for women. The low risk of hematological malignancies was consistent in both men and women, although the number of cases identified with hematological malignancies was lower in women (n = 288) than in men (n = 1467).We further calculated the risk of hematological malignancies by age at identification of AUDs (Table 3). The risks of various types of hematological malignancies were generally low irrespective of the age at identification from the three registries; however, the risks were somewhat lower among those AUDs identified at an older age compared to those identified at a younger age.
Table 2.
Risk of Hematological Malignancies among Individuals with AUDs.
| Disease |
Men |
Women |
All |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| O | SIR | 95% CI | O | SIR | 95% CI | O | SIR | 95% CI | ||||
| Non-Hodgkin lymphoma | 791 | 0.64 | 0.60 | 0.69 | 150 | 0.69 | 0.58 | 0.81 | 941 | 0.65 | 0.61 | 0.69 |
| Diffuse large B cell | 107 | 0.83 | 0.68 | 1.01 | 24 | 0.98 | 0.62 | 1.45 | 131 | 0.86 | 0.72 | 1.02 |
| Follicular | 48 | 0.72 | 0.53 | 0.96 | 14 | 0.72 | 0.39 | 1.21 | 62 | 0.72 | 0.55 | 0.93 |
| Hodgkin disease | 184 | 0.70 | 0.60 | 0.81 | 41 | 0.77 | 0.55 | 1.04 | 225 | 0.71 | 0.62 | 0.81 |
| Mixed cellularity classic | 15 | 0.86 | 0.48 | 1.42 | 3 | 1.18 | 0.22 | 3.49 | 18 | 0.90 | 0.53 | 1.43 |
| Nodular sclerosis classic | 58 | 1.27 | 0.96 | 1.64 | 12 | 0.76 | 0.39 | 1.33 | 70 | 1.14 | 0.89 | 1.44 |
| Myeloma | 167 | 0.53 | 0.45 | 0.61 | 29 | 0.49 | 0.33 | 0.70 | 196 | 0.52 | 0.45 | 0.60 |
| Leukemia | 325 | 0.52 | 0.46 | 0.58 | 68 | 0.46 | 0.36 | 0.59 | 393 | 0.51 | 0.46 | 0.56 |
| Acute lymphatic leukemia | 55 | 0.49 | 0.37 | 0.63 | 17 | 0.57 | 0.33 | 0.91 | 72 | 0.50 | 0.39 | 0.63 |
| Acute myeloid leukemia | 54 | 0.31 | 0.24 | 0.41 | 9 | 0.21 | 0.09 | 0.39 | 63 | 0.29 | 0.22 | 0.37 |
| Chronic myeloid leukemia | 52 | 0.53 | 0.40 | 0.70 | 11 | 0.58 | 0.29 | 1.04 | 63 | 0.54 | 0.41 | 0.69 |
| All | 1467 | 0.60 | 0.57 | 0.63 | 288 | 0.60 | 0.54 | 0.68 | 1755 | 0.60 | 0.57 | 0.63 |
O, observed number of cases; SIR, standardized incidence ratio; CI, confidence interval.
Bold type, 95% CI does not include 1.00.
Table 3.
Risk of Hematological Malignancies among Individuals with AUDs by Age at Identification.
| Disease |
< 40 |
40-60 |
60 + |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| O | SIR | 95% CI | O | SIR | 95% CI | O | SIR | 95% CI | ||||
| Non-Hodgkin lymphoma | 150 | 0.97 | 0.82 | 1.13 | 420 | 0.72 | 0.65 | 0.79 | 371 | 0.53 | 0.47 | 0.58 |
| Diffuse large B cell | 28 | 1.34 | 0.89 | 1.94 | 68 | 0.96 | 0.75 | 1.22 | 35 | 0.57 | 0.40 | 0.79 |
| Follicular | 9 | 0.93 | 0.42 | 1.77 | 34 | 0.77 | 0.53 | 1.08 | 19 | 0.59 | 0.36 | 0.93 |
| Hodgkin disease | 102 | 0.92 | 0.75 | 1.11 | 97 | 0.73 | 0.59 | 0.89 | 26 | 0.36 | 0.23 | 0.52 |
| Mixed cellularity classic | 9 | 1.05 | 0.48 | 2.00 | 7 | 0.95 | 0.38 | 1.97 | 2 | 0.49 | 0.05 | 1.82 |
| Nodular sclerosis classic | 44 | 1.10 | 0.80 | 1.47 | 19 | 1.20 | 0.72 | 1.88 | 7 | 1.23 | 0.49 | 2.56 |
| Myeloma | 15 | 0.98 | 0.55 | 1.62 | 104 | 0.77 | 0.63 | 0.94 | 77 | 0.34 | 0.27 | 0.43 |
| Leukemia | 120 | 0.61 | 0.50 | 0.72 | 160 | 0.55 | 0.47 | 0.65 | 113 | 0.40 | 0.33 | 0.48 |
| Acute lymphatic leukemia | 59 | 0.62 | 0.47 | 0.80 | 12 | 0.37 | 0.19 | 0.64 | 1 | 0.06 | 0.00 | 0.37 |
| Acute myeloid leukemia | 20 | 0.57 | 0.35 | 0.88 | 25 | 0.29 | 0.19 | 0.43 | 18 | 0.19 | 0.11 | 0.30 |
| Chronic myeloid leukemia | 19 | 0.80 | 0.48 | 1.25 | 26 | 0.49 | 0.32 | 0.72 | 18 | 0.45 | 0.26 | 0.71 |
| All | 387 | 0.81 | 0.73 | 0.89 | 781 | 0.68 | 0.64 | 0.73 | 587 | 0.46 | 0.42 | 0.49 |
O, observed number of cases; SIR, standardized incidence ratio; CI, confidence interval.
Bold type, 95% CI does not include 1.00.
In Table 4, we present the risks of hematological malignancies among the siblings with AUDs compared to their siblings without AUDs with adjustment of age. The overall risk was 0.72 (95% CI = 0.65-0.819), and all the subtypes of hematological malignancies showed a decreased risk of OR.
Table 4.
ORs of Hematological Malignancies among Siblings with AUDs Compared to Siblings without AUDs Using Sibling Design Analysis.
| Disease | OR | 95% CI | |
|---|---|---|---|
| Non-Hodgkin lymphoma | 0.72 | 0.61 | 0.85 |
| Hodgkin disease | 0.46 | 0.31 | 0.69 |
| Myeloma | 0.76 | 0.53 | 1.09 |
| Leukemia | 0.57 | 0.46 | 0.71 |
| All | 0.72 | 0.65 | 0.81 |
OR, odds ratio; CI, confidence interval.
Bold type, 95% CI does not include 1.00.
In Table W1, we present our sensitivity analyses for the risk of esophageal and upper aerodigestive tract cancers among individuals with AUDs, and the risk was 2.41 (95% CI = 2.31-2.51) and 2.26 (95% CI = 2.10-2.43), respectively.
Discussion
In this population-based cohort study, a total of 420,489 individuals were identified with AUDs in Sweden. This is, to our best knowledge, the largest study examining the association of AUDs with hematological malignancies. The primary finding in this study was that the risks of hematological malignancies, including non-Hodgkin lymphoma, Hodgkin disease, myeloma, and leukemia, were significantly decreased among individuals with AUDs compared to the general population without AUDs. The risk patterns were similar in both men and women, and the SIR was somewhat lower among AUDs identified at an older age. In addition, by controlling for unmeasured confounding factors using sibling design, the risk patterns were similar to the conventional population-based cohort study.
The low risk of non-Hodgkin lymphoma observed in this study was consistent with a few previous studies [8–12]. The inverse association between non-Hodgkin lymphoma and alcohol consumption was noted in a few previous case-control studies [10–12], and a pool analysis based on these case-control studies finds that the risk of non-Hodgkin lymphoma is 0.83 among alcohol drinkers [8], somewhat lower than our calculated risk of 0.65. We expect that the difference is because individuals identified with AUDs in this study may have been heavier drinkers compared to those in previous studies. A cohort study investigated the relation of alcohol consumption among 35,156 Iowa women to risk of non-Hodgkin lymphoma found that higher alcohol consumption was significantly associated with a decreased risk of non-Hodgkin lymphoma during the 9-year follow-up period (P trend = .03) [9]. Some inconsistent data were reported previously [13–15]. Possible reasons for the observed inconsistencies are different study designs and small numbers of cases. In addition, most previous case-control studies defined alcohol consumption using mailed questionnaire with potential reporting bias, and many of them focused on the associations with specific alcoholic beverages, such as wine or beer. We found an association between AUDs and two subtypes of non-Hodgkin lymphoma, namely, diffuse lymphoma and follicular lymphoma. This agrees with a previous study [8]. Studies examining the associations with Hodgkin lymphoma, myeloma, and leukemia are also limited [7].The decreased risk of Hodgkin lymphoma was also in agreement with previous reports [24,25]; however, the risk for nodular sclerosis classic and mixed cellularity Hodgkin disease was not lower among individuals with AUDs. Previous studies examining the associations between AUDs and myeloma and leukemia did not find consistent risk patterns [26–29]. In contrast, we found that the risks of myeloma and leukemia were lower than the risk of non-Hodgkin lymphoma among individuals with AUDs.
A review article suggests that moderate alcohol consumption can also improve cellular and humoral immune response [30], but a very high amount of alcohol may impair the immune function [30]. On the basis of the fact that AUD cases identified in this study represent a population with excessive alcohol consumption, our observation of the inverse association with hematological malignancies could not be explained through immune mechanisms. Previous studies suggested that antioxidants (resveratrol) in grape skins can reduce the risk of non-Hodgkin lymphoma [31,32]. Unfortunately, we have no information about specific alcoholic beverages among individuals with AUDs; thus, the reverse associations observed in our study could not be totally attributed to consumption of wine drinking. However, it is known that consumption of wine in Sweden has increased greatly during the later half of the 20th century although Sweden is historically with high consumption of distilled beverages and binge drinking [33]. In addition, it is known that a few types of viruses are associated with hematological malignancies [34,35]. For example, the Epstein-Barr virus is associated with lymphoma (Burkitt and extranodal natural killer/T cell non-Hodgkin lymphoma and Hodgkin lymphoma), hepatitis C virus is associated with non-Hodgkin lymphoma, Kaposi sarcoma herpesvirus is associated with primary effusion lymphoma, human immunodeficiency virus is associated with lymphoma, and human T cell lymphotrophic virus is associated with adult T cell leukemia and lymphoma. A review article by Moorer suggests that alcohol can be used for surface disinfection of various types of viruses [36,37]. However, whether alcohol consumption can inactivate various types of viruses in vivo and/or in vitro is still unknown. Although it is widely known that consumption of alcohol can increase the risk of several types of solid cancers [5,6], the mechanisms are still unclear. The protective effect of alcohol on hematological malignancies is somewhat a novel finding compared to their adverse effect, and the potential mechanisms are even unclear, to our knowledge. However, further studies are greatly needed to duplicate our observation, and it is important to include more information regarding other associated risk factors (e.g., smoking, dietary habits, and amount and frequency of alcohol consumed over time) in future studies. Our study did not imply the applications of excessive alcohol consumption to prevent hematological malignancies. Instead, our study promotes research to disentangle the underlying mechanisms of the protective effect of alcohol consumption against hematological malignancies, which may lead to more effective prevention of these malignancies. In addition, it may also be interesting to examine whether the protective effect varied by the type of alcoholic beverage.
An important strength of this study is that all the data were retrieved from Swedish Registers with high quality and almost 100% coverage. In addition, the number of patients included is large enough to guarantee reliable risk estimates. The prospective study design and the completeness of the follow-up of patients are other major strengths of this study. Moreover, we adjusted for a number of confounding factors, such as age, sex, education, and we used the sibling design analysis to control for unmeasured confounding factors. In addition, our sensitivity analyses found that the risk of esophageal and upper aerodigestive tract cancers (Table W1) were greatly increased and consistent with previous reports, suggesting that the AUD cases identified in this study can represent a population with excessive alcohol consumption in general.
One limitation of this study is that AUD cases may represent individuals with severe alcohol consumption, and the results in this study may not be directly applicable to the general population. Another limitation is the lack of information about some individual-level risk factors, such as the amount of alcohol consumption, the presence of smoking, and dietary habits; however, the effects of these risk factors could be somewhat minimized by adjusting for socioeconomic factors such as education level and region of residence.
To summarize, alcohol consumption has a protective effect against hematological malignancies. In particular, individuals with AUDs had low risks of lymphoma, myeloma, and leukemia, and this finding was consistent in men as well as women. However, further studies are needed to confirm our findings and to identity the underlying mechanisms of the protective effect of alcohol consumption against hematological malignancies.
Acknowledgments
The authors thank the CPF's Science Editor Stephen Gilliver for his valuable comments on the text.
Footnotes
J.J., K.S., and J.S. were responsible for the study concept and design. J.S. and K.S. obtained funding and acquired the data. J.J. analyzed and interpreted the data, did the statistical analysis, and drafted the manuscript. All authors revised it for important intellectual content. J.S. is the guarantor.
This work was supported by grants to K.S. from the Swedish Research Council (K2009-70X-15428-05-3 and K2012-70X-15428-08-3), to J.S. from the Swedish Council for Working Life and Social Research (2007–1754) as well as Avtal om Läkarutbildning och Forskning funding from Region Skåne awarded to J.S., K.S., and J.J. The funding agencies had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. The researchers were independent of the funding agencies. Conflict of interests: None.
Ethical approval: This study was approved by the Regional Ethical Review Board of Lund University in Sweden.
Supplementary information is available at Leukemia's website.
This article refers to supplementary material, which is designated by Table W1 and is available online at www.neoplasia.com.
Supplementary Material
Table W1.
Risk of Cancers in the Esophagus and Upper Aerodigestive Tract among Individuals with AUDs.
| Diseases |
Male |
Female |
All |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| O | SIR | 95% CI | O | SIR | 95% CI | O | SIR | 95% CI | ||||
| Upper aerodigestive tract | 1950 | 2.27 | 2.17 | 2.37 | 320 | 3.82 | 3.42 | 4.27 | 2270 | 2.41 | 2.31 | 2.51 |
| Esophagus | 641 | 2.12 | 1.96 | 2.29 | 94 | 4.10 | 3.31 | 5.02 | 735 | 2.26 | 2.10 | 2.43 |
O, observed number of cases; SIR, standardized incidence ratio; CI, confidence interval.
Bold type, 95% CI does not include 1.00.
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