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. 2023 Sep 13;116(2):309–315. doi: 10.1093/jnci/djad187

Autoimmune disease and the risk of anal cancer in the US population aged 66 years and over

Minkyo Song 1,✉, Eric A Engels 2, Megan A Clarke 3, Aimée R Kreimer 4, Meredith S Shiels 5
PMCID: PMC10852610  PMID: 37701981

Abstract

Background

In the United States, anal squamous cell carcinoma rates have increased rapidly, particularly among women 50 or older than 66 years of age. As immunosuppression is associated with increased risk, autoimmune conditions may be associated with greater risk of anal squamous cell carcinoma.

Methods

We conducted a population-based, case-control study using Surveillance, Epidemiology, and End Results–Medicare data (2000-2017). Anal squamous cell carcinoma cases (n = 4505) were matched to 200 000 cancer-free controls. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between 47 autoimmune conditions diagnosed before selection, identified using Medicare claims, and anal squamous cell carcinoma. The Bonferroni threshold was used to correct for multiple comparisons. Population attributable fractions were calculated for conditions nominally associated with anal squamous cell carcinoma.

Results

In total, 18% of anal squamous cell carcinoma cases and 15% of cancer-free controls had a diagnosed autoimmune condition. Any autoimmune condition was associated with an increased risk of anal squamous cell carcinoma (OR = 1.11, 95% CI = 1.02 to 1.21; population attributable fraction = 1.8%). Anal squamous cell carcinoma was associated with systemic lupus erythematosus (OR = 1.79, 95% CI = 1.32 to 2.42; population attributable fraction = 0.4%) and nominally associated (P < .05) with sarcoidosis (OR = 2.09, 95% CI = 1.30 to 3.37; population-attributable fraction = 0.2%) and psoriasis (OR = 1.28, 95% CI = 1.06 to 1.56; population attributable fraction = 0.5%). Stratified by sex, only women showed statistically significant associations for systemic lupus erythematosus (OR = 1.97, 95% CI = 1.46 to 2.68). Statistically significant interaction was observed by sex for psoriasis (men vs women: OR = 1.68 [95% CI = 1.03 to 4.28] vs OR = 1.12 [95% CI = 0.88 to 1.43]) and polymyalgia rheumatica (OR = 0.33 [95% CI = 0.12 to 0.89] vs OR = 0.99 [95% CI = 0.75 to 1.30]).

Conclusion

Systemic lupus erythematosus, sarcoidosis, and psoriasis were associated with a moderately increased risk of anal squamous cell carcinoma. Given these conditions’ rarity and moderate associations with anal squamous cell carcinoma, autoimmune diseases cannot explain the rising trend in this disease.

Anal squamous cell carcinoma, the primary histologic type of anal cancer, is relatively rare, but rates have increased rapidly over time in the United States and other parts of the world (1). Notably, in the United States, this trend has been most pronounced among women 50 to 69 years of age, increasing by 5.0% per year (2-4) Anal cancer is among the most rapidly increasing cancer types in the United States, and it may soon overtake cervical cancer as the most common human papillomavirus (HPV)–linked cancer in older adult women, where rates have decreased due to cervical cancer screening (3).

Anal squamous cell carcinoma is predominantly caused by infection with HPV, which causes nearly 90% of cases (5). Rates of anal squamous cell carcinoma have sharply increased in immunosuppressed populations, particularly among people with HIV infection (6), where rates are elevated nearly 20-fold compared with the general population (7). A prior study showed that anal squamous cell carcinoma occurring among people with HIV have strongly influenced trends among men but have had no impact on trends among women (8). The risk of anal cancer also increased among solid organ transplant recipients, who receive immunosuppressive antirejection medications (9).

Immunosuppressant drugs can also be used to treat autoimmune diseases, which may lead to an increased risk of anal squamous cell carcinoma in the presence of anal HPV infection. There is some prior evidence that elevated rates of anal cancer may occur among those with autoimmune disease, but these studies were limited to certain types of autoimmune diseases, included data more than a decade old, and did not stratify by sex (10,11). Many autoimmune conditions disproportionately affect women, and their prevalence is increasing over time; thus, common autoimmune diseases could be contributing to rising rates of anal squamous cell carcinoma if they are associated with increased risk. In a large nested case-control study, we investigated whether autoimmune conditions are associated with anal squamous cell carcinoma among men and women 66 years of age and older.

Methods

The Surveillance, Epidemiology, and End Results (SEER)–Medicare database links 2 large, population-based data sources: cancer registries from the National Cancer Institute’s SEER program and claims data from Medicare (12). The SEER program collects and publishes information about cancer incidence, mortality, and survival from population-based cancer registries, covering approximately 48% of the US population (13). Medicare is a federally funded health insurance program for approximately 97% of the US population 65 years of age or older. All Medicare beneficiaries are entitled to Part A coverage (for hospital inpatient treatment), while around 96% of beneficiaries have Part B coverage (physician and outpatient services), as well.

We conducted a nested case-control study using SEER-Medicare data (14). Eligible patients with anal squamous cell carcinoma were 66 to 99 years of age, with a first cancer diagnosis and no prior cancer history, identified in SEER during 1999-2017. Cancers diagnosed only at autopsy or by death certificate were excluded. We defined anal cancer cases using the International Classification of Diseases for Oncology, Third Edition, codes C21.0-C21.2 and C21.8 (15). Invasive anal squamous cell carcinoma cases (behavior = 3) were further classified by histology (8050-8076, 8083-8084, and 8123-8124).

From the 5% random sample of Medicare beneficiaries, 200 000 population-based controls were chosen at random and frequency matched to the invasive anal squamous cell carcinoma cases by selection year, age category (66-69, 70-74, 75-79, 80-84, and 85-99 years), sex, and race (non-White, White). Controls could be sampled more than once over the course of a calendar year and could later turn into cases, but had to be cancer free on July 1 of the selection year.

Autoimmune disease diagnoses occurring before cancer diagnosis were ascertained by using Medicare claims. To avoid any potential bias of differential assessment of autoimmune conditions between cases and controls, we did not include claims for autoimmune diseases from the year leading up to the cancer diagnosis or the corresponding period in controls. Therefore, both cases and controls had to have at least 13 months of Medicare coverage before their cancer diagnosis or before being selected as a control. We excluded individuals covered under health maintenance organizations because they are not required to submit itemized claims to Medicare.

We selected a priori 47 autoimmune conditions for evaluation based on International Classification of Diseases, Tenth Revision (ICD-10) codes (Supplementary Table 1, available online). We considered only those conditions documented in at least 1 hospital claim or 2 clinician or outpatient claims at least 30 days apart. The results for 29 autoimmune conditions that had fewer than 10 exposed cases are not presented separately in our study (alopecia areata, amyotrophic lateral sclerosis, ankylosing spondylitis, aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, Behçet disease, celiac disease, dermatomyositis, dermatitis herpetiformis, discoid lupus erythematosus, erythema nodosum, granulomatosis with polyangiitis, Guillain-Barré syndrome, hypersensitivity angiitis, immune thrombocytopenic purpura, Kawasaki disease, membranous nephropathy, myasthenia gravis, polyarteritis nodosa, polymyositis, primary biliary cirrhosis, primary sclerosing cholangitis, reactive arthritis, rheumatic fever, scleritis, Takayasu arteritis, uveitis, and vitiligo) in accordance with the SEER-Medicare data use agreement to protect patient confidentiality.

We also used ICD-10 codes in Medicare claims to identify smoking and alcohol abuse for adjustment, though these behaviors are incompletely ascertained in claims data (Supplementary Table 2, available online). We assessed the socioeconomic status of individuals based on the median income of the area in which they lived and calculated health-care utilization as the average number of physician claims per year in the time period at least 13 months before diagnosis or selection. Colorectal screening procedures were included in the model to control for incidental detection and were ascertained based on outpatient claims for a colonoscopy or sigmoidoscopy 12 months before diagnosis or selection (Supplementary Table 3, available online).

Multivariable unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each autoimmune condition with invasive anal squamous cell carcinoma. To account for the fact that some controls were selected multiple times over different years and for control individuals who later developed cancer, the variance of the odds ratio was adjusted (14). Models were adjusted for matching variables (age, sex, race or ethnicity, calendar year of diagnosis or selection) as well as average number of physician visits per year, zip code median income, smoking status, and ever having received colonoscopy or sigmoidoscopy. A sensitivity analysis was conducted to exclude individuals with immunosuppressive (including HIV infection) and transplant conditions (N = 849; definition by ICD-10 in Supplementary Table 4, available online).

We calculated population attributable fractions for overall and selective autoimmune conditions with P < .05 using the following formula: (prevalence of autoimmune condition in cases) × (OR – 1)/OR (16). We present results using a nominal P < .05, but because of the large number of statistical tests (ie, 47 autoimmune conditions), we used a Bonferroni correction to determine statistical significance (cutoff of P < .05/47 = .001). Significant associations were further explored for heterogeneity by sex using Cochrane Q statistics. As incidence rates of anal squamous cell carcinoma among those with autoimmune disease could not be assessed using a case-control design, we used an indirect approach. Sex-specific incidence rates of anal squamous cell carcinoma among individuals with autoimmune diseases overall and for select conditions that were statistically significantly or nominally associated with anal cancer risk were estimated by multiplying odds ratios by incidence rates estimated from data from SEER-22 cancer registries using the same definition of anal squamous cell carcinoma outlined earlier. Anal squamous cell carcinoma rates among those 66 years of age or older were estimated from data from 2016-2020. All statistical analyses were performed using SAS, version 9.4 (SAS Institute Inc, Cary, NC) and SEER*Stat software, version 8.4.1.2 (seer.cancer.gov/seerstat).

Results

The characteristics of SEER-Medicare controls (n = 200 000) and patients diagnosed with anal squamous cell carcinoma (n = 4505) are shown in Supplementary Table 5 (available online). The mean (SD) ages at selection were 75.8 (7.2) and 75.7 (7.2) years for controls and anal squamous cell carcinoma cases, respectively. Approximately 70% of patients with anal squamous cell carcinoma cases and control individuals were women. Year of diagnosis or selection and race or ethnicity distribution were similar between anal squamous cell carcinoma cases and controls. Among controls and anal squamous cell carcinoma cases, the average (SD) number of physician claims per year was 13.0 (11.1) and 13.1 (12.1), and the average (SD) number of months of Medicare coverage was 77.9 (53.0) and 78.8 (54.2). More patients with anal squamous cell carcinoma than control individuals smoked (42.2% vs 36.6%), drank alcohol (14.6% vs 9.4%), and had ever had a colonoscopy and/or sigmoidoscopy (40.1% vs 37.4%).

Overall, 17.6% of patients with anal squamous cell carcinoma and 15.5% of control individuals had any of the a priori selected 47 autoimmune conditions. Having any of these 47 autoimmune conditions was positively associated with anal squamous cell carcinoma (OR = 1.11, 95% CI = 1.02 to 1.21). The associations between 18 individual autoimmune conditions with more than 10 cases each and anal squamous cell carcinoma are presented in Figure 1 and Supplementary Table 6 (available online). The strongest association was observed for sarcoidosis (18 in the anal squamous cell carcinoma group; OR = 2.09, 95% CI = 1.30 to 3.37), followed by systemic lupus erythematosus (SLE; 45 in the anal squamous cell carcinoma group: OR = 1.79, 95% CI = 1.32 to 2.42) and psoriasis (112; OR = 1.28, 95% CI = 1.06 to 1.56), of which only SLE was statistically significant after Bonferroni correction. The findings from the sensitivity analyses, excluding those with immunosuppressive (including HIV infection) and transplant conditions, remain the same, result in an OR of 1.12 (95% CI = 1.03 to 1.22) (rest of the data not shown).

Figure 1.

Figure 1.

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Association between selected autoimmune conditions and anal squamous cell carcinoma. Odds ratios are adjusted for age, sex, race or ethnicity, calendar year of cancer diagnosis or control selection, average number of clinician visits per year, zip code median income, smoking status, and colonoscopy or sigmoidoscopy. *P < .05, ** P < .05/47 = .001. CI = confidence interval; OR = odds ratio.

Figure 2 shows a similar analysis stratified by sex. Women had a higher prevalence of any autoimmune condition in the case group (19.7%) and the control group (17.3%) than men (12.6% vs 11.2%, respectively). Five autoimmune conditions (SLE, systemic sclerosis, scleroderma, giant cell arteritis, Sjögren syndrome) could not be analyzed in men because of the small number of cases. Among these, sarcoidosis (OR = 2.14, 95% CI = 1.27 to 3.61) and scleroderma (OR = 1.51, 95% CI = 1.00 to 2.28) were nominally significant, and SLE (OR = 1.97, 95% CI = 1.46 to 2.68) was statistically significant after Bonferroni correction in women. Although not statistically significant in women, there was a statistically significant association for psoriasis (OR = 1.68, 95% CI = 1.03 to 4.28) and polymyalgia rheumatica (OR = 0.33, 95% CI = 0.12 to 0.89) in men (P < .05 for interaction by sex).

Figure 2.

Figure 2.

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Association between select autoimmune conditions and anal squamous cell carcinoma, by sex. Odds ratios are adjusted for age, sex, race or ethnicity, calendar year of cancer diagnosis or control selection, average number of clinician visits per year, zip code median income, smoking status, and colonoscopy or sigmoidoscopy. *P < .05. CI = confidence interval; OR = odds ratio.

The population attributable fractions for various autoimmune conditions in individuals with anal squamous cell carcinoma were as follows: 1.8% for total autoimmune conditions, 0.5% for psoriasis, 0.4% for SLE, and 0.2% for sarcoidosis in the overall population (Supplementary Table 6, available online). In the context of women, the population attributable fractions were 2.0% for any autoimmune conditions, 1.2% for scleroderma, 1.1% for sarcoidosis, and 0.7% for SLE. For men, the respective fractions were 1.2% for any autoimmune conditions, 1.3% for psoriasis, and 0.3% for pure red cell aplasia. The estimated crude anal squamous cell carcinoma incidence rates for autoimmune conditions were observed to be 6.5 per 100 000 individuals. When examining specific diseases, the incidence rates were found to be 10.4, 12.1, and 7.4 per 100 000 individuals for SLE, sarcoidosis, and psoriasis, respectively. In terms of sex-specific incidence rates, among women, the incidence rates were 14.2, 15.4, and 10.9 per 100 000 individuals for SLE, sarcoidosis, and scleroderma, respectively, while among men, they were 6.9, 8.6, and 1.4 per 100 000 individuals for psoriasis, pure red cell aplasia, and polymyalgia rheumatica.

Discussion

In a large, population-based, nested, case-control study, we found that having an autoimmune condition was positively and moderately associated with anal squamous cell carcinoma. Among a comprehensive list of 47 autoimmune conditions investigated, SLE was statistically significantly associated with increased risk of anal squamous cell carcinoma, and sarcoidosis and psoriasis showed nominal positive associations. The associations with psoriasis and polymyalgia rheumatica differed between women and men, and SLE was stiatistically significant only in women.

Anal cancer is caused by anal HPV infection, primarily HPV-16 (17). Immunosuppression strongly increases the risk of anal squamous cell carcinoma. For example, the degree of immunosuppression among people with HIV, including prior AIDS diagnosis, nadir CD4 cell count, and duration of CD4 cell count below 200, is associated with anal cancer risk (7,18).

Similarly, immune function may be impaired in patients with autoimmune disease because of alterations in the intrinsic immune system, immunosuppressive treatments, or a combination of the 2. Current treatments, such as corticosteroids, immunosuppressive drugs (eg, methotrexate, azathioprine, cyclophosphamide), and biologic agents (eg, tumor necrosis factor inhibitors) suppress immunity. In general, immunosuppressive treatments work by reducing the activity or number of immune cells, inhibiting the production of inflammatory chemicals, or targeting specific molecules or cells involved in the immune response. Observational studies have documented increased risk of cancer associated with the use of immunosuppressants, such as in the example of thiopurines and tumor necrosis factor inhibitors with lymphoma in patients with inflammatory bowel disease or rheumatoid arthritis (19,20). As a result, people with autoimmune disorders may be more susceptible to anal squamous cell carcinoma. Having any of the examined common autoimmune conditions increased the risk of anal squamous cell carcinoma by 11%. Several national registry-based studies investigated various autoimmune conditions with anal squamous cell carcinoma (10,11). The overall association between autoimmune diseases and anal squamous cell carcinoma was moderately higher (30%-60%) than in those without autoimmune diseases, but these results were based on fewer than 100 anal squamous cell carcinoma cases compared with our approximately 4500 cases. Furthermore, we have investigated a wider range of autoimmune conditions (47) than the previous 24 to 28 conditions. Several other studies have included anal cancer as part of colorectal cancer analysis or were not able to differentiate the histologic types (21).

Individuals with SLE had twice the risk of anal squamous cell carcinoma than those without the disease in our study. SLE has consistently been reported to be positively associated with anal squamous cell carcinoma, with a range of relative risk estimates between 2 and 7 in population-based studies (10,22,23). Although gastrointestinal involvement is common in patients with SLE, colonic involvement is rare and presents in the form of vasculitis or complications that occur due to immune complex deposition in smooth muscle cells (24,25). In addition to the possible effect of immunosuppressants used for the disease, 1 possible explanation for the positive association with anal squamous cell carcinoma in patients with SLE is their higher risk of genital HPV infection, perhaps because of impaired clearance of the virus secondary to disease-related or therapy-induced immunodeficiency (26,27). Higher risk of potentially virus-associated cancers in these patients provides hints to altered immunity’s role in infection-cancer association (23).

Despite the lack of Bonferroni significance, we found potential positive associations between 2 other autoimmune diseases and anal squamous cell carcinoma. Sarcoidosis is an autoimmune disease characterized by granulomatous inflammation that can affect any organ of the body, most commonly the lungs, skin, or lymph nodes (28). The evidence for a link between sarcoidosis and anal squamous cell carcinoma is limited, with 1 previous population-based study reporting a 3.5 times higher risk in patients with sarcoidosis than in the general population (10), whereas another study reported a statistically nonsignificant positive association (11). Perianal involvement of sarcoidosis is rare, with only a few cases reported in the literature (29-31). Interestingly, patients with sarcoidosis are at higher risk of squamous cell skin cancer (32) and squamous cell lung cancer (33). Psoriasis is a relatively common chronic inflammatory skin disease that results in hyperproliferation and abnormal differentiation of the dermis. Two previous population-based studies have similarly reported a 3-fold increased risk of anal squamous cell carcinoma in patients with psoriasis compared with the general population (10,11). Psoriasis is also reported to be associated with HPV-related cancers, such as penile, vulvar, and oropharyngeal squamous cell carcinomas (34,35).

Both anal squamous cell carcinoma and autoimmune diseases occur more often in women (36). Therefore, in sex-stratified analysis, some associations could be analyzed only in women. The range of the magnitude of association in women did not differ from men, with a maximum odds ratio of 2.14 for sarcoidosis. Interestingly, the prevalence of psoriasis does not differ between women and men, but men have more severe symptoms (37). Perhaps the severity of the disease may be associated with the stronger association in men with anal squamous cell carcinoma observed in our study. Polymyalgia rheumatica occurs twice as often in women than in men (38). There has been inconsistent report between polymyalgia rheumatic and cancer risk (39,40), and our findings of a nominal inverse association in men requires further investigation.

Part of the motivation for studying the associations between autoimmune disease and anal squamous cell carcinoma was to assess whether the rising prevalence of autoimmune disease may have contributed to rising rates of anal squamous cell carcinoma, particularly among women, among which HIV has had little impact (8). Though some associations were identified, the conditions that were statistically significantly associated with anal squamous cell carcinoma occurred too infrequently in the general population to influence general population trends. For example, though SLE increases anal squamous cell carcinoma risk almost 2-fold, the population attributable fraction was 0.4% in the overall population and 0.7% in women.

There is currently a lack of consensus on a standardized approach for anal squamous cell carcinoma screening, though a recent trial showed that the treatment of high-grade anal squamous intraepithelial lesions in people with HIV reduced the risk of anal cancer (41). Given the rarity of anal squamous cell carcinoma in the general population, it is impractical to conduct universal screening for this cancer. As an alternative, targeted screening for certain groups with elevated risk of anal cancer compared with the general population, including people with HIV; men who have sex with men; women diagnosed with HPV-related precancerous lesions or cancer of the cervix, vulva, or vagina; solid organ transplant recipients; and patients with autoimmune conditions, may be considered. Our findings align with the anal cancer risk scale developed by Clifford et al. (9), which summarizes anal cancer incidence rates among different groups, including those with non–HIV-related autoimmune conditions. Specifically, we show an elevated risk of 10.4 for SLE, which is similar to the rate of 10 per 100 000 individuals (95% CI = 5 to 19), reported by Clifford et al. We also identified certain conditions with elevated risks that were not assessed as part of the Clifford meta-analysis, including sarcoidosis and psoriasis, which were associated with risks of 12.1 and 7.4 per 100 000 individuals, respectively, among all individuals. Among women, anal cancer risk among those with SLE was 14.2, 15.4 among those with sarcoidosis, and 10.9 among those with scleroderma. These risk estimates are comparable to and, in some cases, higher than those among women with prior diagnoses of cervical and vaginal cancer and precancer, suggesting that women 66 years of age or older with SLE, sarcoidosis, or scleroderma should be considered alongside women with a history of precancerous or cancerous lesions of the cervix or vagina when making clinical recommendations based on the principle of equal management for populations with similar absolute risks (9).

Our study has important strengths. First, it was conducted using a population-based design and a large sample size. SEER-Medicare provides a representative sample of US adults aged 66 years and older and offers reliable data on cancer diagnoses by cancer registries. Consequently, we were able to assess more than 4500 confirmed anal squamous cell carcinoma cases and examine a vast array of rare autoimmune conditions. Second, we were able to minimize reverse causation by restricting our analysis to autoimmune diseases diagnosed more than 1 year before anal squamous cell carcinoma diagnosis. Finally, we were able to adjust for possible confounding factors that other population-based studies producing standardized incidence ratios could not. Patients with autoimmune disease may have undergone more frequent surveillance and thus were prone to detection bias; we tried to mitigate that bias by adjusting for physician visits per year and colorectal cancer screening.

Our study has some limitations that should be noted, as well. We were unable to consider factors such as anal HPV infection, anogenital warts, sexual activity, or other types of lowered immunity that may have confounded the association between autoimmune conditions and anal squamous cell carcinoma. Additionally, we did not have information about autoimmune disease treatments, which may increase cancer risk (42). Furthermore, our study population was limited to individuals 66 years of age or older, so the results may not apply to younger populations, including those aged 50 to 65 years, where statistically significant increases in anal squamous cell carcinoma have been observed. Additionally, medical claims data are not always accurate and may have led to the underdiagnosis of autoimmune conditions, especially because many autoimmune conditions develop at younger ages and severity diminishes with age. We anticipate that our use of a strict definition to identify autoimmune conditions—requiring either 1 inpatient claim or 2 clinician or outpatient claims—improved the specificity of our classification and showed that an underestimation of autoimmune conditions would have pushed the observed associations toward the null. ICD-10 codes were used to detect tobacco and alcohol consumption, but these codes inadequately reflect the actual behavioral health patterns and may have low sensitivity. In addition, the claims codes for colonoscopies cannot distinguish between diagnostic and screening procedures. Finally, the low prevalence of autoimmune conditions and anal squamous cell carcinoma made it difficult to detect small effect sizes accurately.

To our knowledge, this study is the largest to date on the association between autoimmune diseases and anal squamous cell carcinoma, stratified by sex. We investigated the most comprehensive list of various autoimmune conditions. Some of our significant findings corroborate those in the literature, but we did not find any conditions with a strong association with a high prevalence to explain the rising trend in anal cancer in the Medicare population.

Supplementary Material

djad187_Supplementary_Data
Click here for additional data file. (199.4KB, pdf)

Acknowledgements

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Cancer Institute; Information Management Services, Inc; and the SEER program tumor registries in the creation of the SEER-Medicare database.

The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention’s National Program of Cancer Registries under cooperative agreement 1NU58DP007156; the National Cancer Institute’s SEER program under contract No. HHSN261201800032I awarded to the University of California, San Francisco, No. HHSN261201800015I awarded to the University of Southern California, and No. HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the state of California, Department of Public Health, the National Cancer Institute, or the Centers for Disease Control and Prevention or their contractors and subcontractors.

We also thank Mike Barrett at Information Management Services, who provided technical support for which he was compensated.

The funder had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication. The funder did review the paper before publication.

This manuscript was published in abstract form (general poster session) at the American Association for Cancer Research Special Conference on Aging and Cancer; November 17-20, 2022; San Diego, California.

Contributor Information

Minkyo Song, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Eric A Engels, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Megan A Clarke, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Aimée R Kreimer, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Meredith S Shiels, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Data availability

The data underlying this article were provided by SEER-Medicare with permission under a data use agreement. Per the data use agreement, data will not be shared, but SEER-Medicare data are available to investigators for research purposes and can be requested from SEER-Medicare at https://healthcaredelivery.cancer.gov/seermedicare/obtain/.

Author contributions

Minkyo Song, MD, PhD (Conceptualization; Data curation; Formal analysis; Methodology; Writing—original draft; Writing—review & editing), Eric A. Engels, MD (Methodology; Writing—review & editing), Megan A. Clarke, PhD (Writing—review & editing), Aimée R. Kreimer, PhD (Writing—review & editing), Meredith S. Shiels, PhD (Conceptualization; Data curation; Methodology; Supervision; Writing—original draft; Writing—review & editing)

Funding

This research was supported in part by the Intramural Research Program of the National Cancer Institute.

Conflicts of interest

The authors have nothing to declare.

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Associated Data

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Supplementary Materials

djad187_Supplementary_Data
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Data Availability Statement

The data underlying this article were provided by SEER-Medicare with permission under a data use agreement. Per the data use agreement, data will not be shared, but SEER-Medicare data are available to investigators for research purposes and can be requested from SEER-Medicare at https://healthcaredelivery.cancer.gov/seermedicare/obtain/.

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