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Risk factors for colorectal cancer significantly vary by anatomic site
  1. Joshua Demb1,
  2. Ashley Earles2,
  3. María Elena Martínez1,3,
  4. Ranier Bustamante2,
  5. Alex K Bryant4,
  6. James D Murphy4,
  7. Lin Liu1,2,3,
  8. Samir Gupta1,5,6
  1. 1Moores Cancer Center, University of California San Diego, La Jolla, California, USA
  2. 2Department of Research, VA San Diego Healthcare System, San Diego, California, USA
  3. 3Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States
  4. 4Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA
  5. 5Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
  6. 6Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, CA, United States
  1. Correspondence to Dr Samir Gupta; s1gupta{at}


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
  • epidemiology
  • 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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