<span class="paragraphSection"><div class="boxTitle">Abstract</div>We expanded and updated our colon cancer risk model to evaluate colorectal cancer (CRC) and whether subsite-specific risk models are warranted. Using data from 1980–2010 for 90,286 women enrolled in the Nurses’ Health Study, we performed competing-risks regression and tests for subsite heterogeneity (proximal colon: <span style="font-style:italic;">n</span> = 821; distal colon: <span style="font-style:italic;">n</span> = 521; rectum: <span style="font-style:italic;">n</span> = 376). Risk factors for CRC were consistent with those in our colon cancer model. Processed meat consumption was associated with a higher risk of distal (hazard ratio (HR) = 1.45; <span style="font-style:italic;">P</span> = 0.02) but not proximal (HR = 0.95; <span style="font-style:italic;">P</span> = 0.72) colon cancer. Smoking was associated with both colon (HR = 1.21) and rectal (HR = 1.27) cancer and was more strongly associated with proximal (HR = 1.31) than with distal (HR = 1.04) colon cancer (<span style="font-style:italic;">P</span> = 0.029). We observed a significant trend of cancer risk for smoking in subsites from the cecum (HR = 1.41) to the proximal colon (excluding the cecum; HR = 1.27) to the distal colon (HR = 1.04; <span style="font-style:italic;">P</span> for trend = 0.040). The <span style="font-style:italic;">C</span> statistics for colorectal (<span style="font-style:italic;">C</span> = 0.607), colon (<span style="font-style:italic;">C</span> = 0.603), and rectal (<span style="font-style:italic;">C</span> = 0.639) cancer were similar, although <span style="font-style:italic;">C</span> was slightly higher for rectal cancer. Despite evidence for site-specific differences for several risk factors, overall our findings support the application of risk prediction models for colon cancer to CRC.</span>
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