Objective To conduct an anatomic site-specific case–control study of candidate colorectal cancer (CRC) risk factors.
Design Case–control study of US veterans with >1 colonoscopy during 1999–2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs.
Results 21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95).
Conclusion Candidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.
- colorectal cancer
- cancer epidemiology
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LL and SG are co-senior authors.
JD and AE are co-first authors.
Contributors Concept and design: JD, AE, RB, LL, AKB, JM, MEM, SG. Analysis and interpretation of data: JD, AE, RB, LL, SG. Drafting of manuscript: JD, AE, RB, LL, AKB, JM, MEM, SG. Critical revision of the manuscript for important intellectual content: JD, AE, RB, LL, AKB, JM, MEM, SG. Statistical analysis: JD, RB, LL, SG. Obtained funding: SG.
Funding This research was supported by the VA Health Services Research and Development (Grant No 5I01HX001574-04, PI: SG) and the National Cancer Institute/National Institutes of Health (Grant No 1R37CA222866-01, PI: SG; Grant No 1F32CA239360-01, PI: JD).
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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