Background: Most studies of colorectal cancer (CRC) risk factors pool cases across anatomical sites, though tumor characteristics and embryologic origins differ. Our aim was to conduct a site-stratified (proximal, distal, rectal) case control study of candidate risk factors for CRC.

Methods: Our study base was US Veterans with >1 colonoscopy 1999-2011. CRC cases at baseline colonoscopy were identified with the Veterans Affairs Central Cancer Registry. Controls had normal colonoscopy without biopsy, no history of CRC, and no CRC within 3 years of index colonoscopy. Age, sex, race/ethnicity, body mass index (BMI), diabetes, and smoking were considered candidate risk factors. Primary outcome was CRC, stratified by site. Site-specific odds ratios (OR) and 95% confidence intervals (CI) for each risk factor were computed with unadjusted and adjusted multinomial logistic regression models.

Results: We identified 21,739 CRC cases and 616,323 normal colonoscopy controls. For cases combined vs. controls, median age was 68 vs. 61 years, 98% vs. 95% were male, median BMI was 27.8 vs. 28.8 kg/m2, 28% vs. 24% had diabetes, and 25% vs. 29% were non-smokers; race/ethnicity was similar. Presence and strength of associations differed by risk factor and CRC site (Table). Smoking was more closely associated with rectal (OR=1.84) than proximal (OR=1.59) or distal cancer (OR=1.50). Diabetes was more closely associated with proximal than distal or rectal cancer (OR=1.28, 1.17 and 1.12, respectively). Blacks had reduced odds for rectal (OR=0.89), but increased odds for distal (OR=1.27) and particularly proximal cancer (OR=1.60) when compared to non-Hispanic whites. For males vs. females, odds of rectal was higher than distal or proximal cancer (OR=2.64, 1.95 and 1.32, respectively).

Conclusions: Presence and strength of association of cancer risk factors may differ by CRC site. Site should be a key consideration in future studies of CRC risk.

Table 1.

Site specific risk factors for 21,739 CRC cases compared to 616,323 normal colonoscopy controls

  Anatomic Site of CRC*  
 Proximal (n=7,686) Distal (n=7,036) Rectal (n=7,017) 
Candidate Risk Factor OR (CI) OR (CI) OR (CI) 
Age, years† 1.100 (1.096-1.103) 1.065 (1.062-1.069)‡ 1.055 (1.051- 1.059)‡§ 
Gender, male vs. female 1.318 (1.080-1.608) 1.950 (1.538-2.471)‡ 2.636 (2.006-3.463)‡ 
Race/ethnicity    
Black vs. non-Hispanic white 1.596 (1.480-1.720) 1.270 (1.167-1.381)‡ 0.886 (0.808-0.971)‡§ 
Hispanic vs. non-Hispanic white 1.291 (1.123-1.485) 1.531 (1.337-1.753) 1.219 (1.053-1.411)§ 
Asian vs. non-Hispanic white 0.872 (0.634-1.201) 0.917 (0.662-1.272) 0.556 (0.371-0.832) 
BMI, kg/m2† 0.994 (0.988-1.000) 1.005 (0.999-1.012)‡ 0.963 (0.957-0.970)‡§ 
Diabetes, yes vs. no 1.278 (1.196-1.366) 1.170 (1.089-1.257) 1.119 (1.038-1.207)‡ 
Smoking    
Current vs. never 1.594 (1.476-1.722) 1.500 (1.383-1.627) 1.837 (1.695-1.992)‡§ 
Former vs. never 0.997 (0.926-1.073) 1.082 (1.001-1.171) 1.085 (0.998-1.119) 
  Anatomic Site of CRC*  
 Proximal (n=7,686) Distal (n=7,036) Rectal (n=7,017) 
Candidate Risk Factor OR (CI) OR (CI) OR (CI) 
Age, years† 1.100 (1.096-1.103) 1.065 (1.062-1.069)‡ 1.055 (1.051- 1.059)‡§ 
Gender, male vs. female 1.318 (1.080-1.608) 1.950 (1.538-2.471)‡ 2.636 (2.006-3.463)‡ 
Race/ethnicity    
Black vs. non-Hispanic white 1.596 (1.480-1.720) 1.270 (1.167-1.381)‡ 0.886 (0.808-0.971)‡§ 
Hispanic vs. non-Hispanic white 1.291 (1.123-1.485) 1.531 (1.337-1.753) 1.219 (1.053-1.411)§ 
Asian vs. non-Hispanic white 0.872 (0.634-1.201) 0.917 (0.662-1.272) 0.556 (0.371-0.832) 
BMI, kg/m2† 0.994 (0.988-1.000) 1.005 (0.999-1.012)‡ 0.963 (0.957-0.970)‡§ 
Diabetes, yes vs. no 1.278 (1.196-1.366) 1.170 (1.089-1.257) 1.119 (1.038-1.207)‡ 
Smoking    
Current vs. never 1.594 (1.476-1.722) 1.500 (1.383-1.627) 1.837 (1.695-1.992)‡§ 
Former vs. never 0.997 (0.926-1.073) 1.082 (1.001-1.171) 1.085 (0.998-1.119) 

* Multinomial analyses adjusted for other risk factors, as well as year of colonoscopy, 1999-2011

† by one unit increment

‡ p<0.05 when compared to proximal cancer

§ p<0.05 when compared to distal cancer

CRC, colorectal cancer; BMI, body mass index.

Citation Format: Samir Gupta, Ranier Bustamante, Ashley Earles, Maria E. Martinez, Karen Messer, Christina D. Williams, Andrew J. Gawron, Tonya Kaltenbach, Lin Liu. Site specific risk factors for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 281. doi:10.1158/1538-7445.AM2017-281