Association Between Risk Factors for Colorectal Cancer and Risk of Serrated Polyps and Conventional Adenomas.

Background & Aims: Serrated polyps (SPs) and conventional adenomas are precursor lesions for colorectal cancer (CRC), but they are believed to arise via distinct pathways. We characterized risk factor profiles for SPs and conventional adenomas in a post hoc analysis of data from 3 large prospective studies.

Methods: We collected data from the Nurses' Health Study, the Nurses' Health Study 2, and the Health Professionals Follow-up Study on subjects who developed SPs or conventional adenomas. Our analysis comprised 141,143 participants who had undergone lower gastrointestinal endoscopy, provided updated diet and lifestyle data every 2-4 years, and were followed until diagnosis of a first polyp. We assessed 13 risk factors for CRC in patients with SPs or conventional adenomas and examined the associations according to histopathology features.

Results: We documented 7945 SPs, 9212 conventional adenomas, and 2382 synchronous SPs and conventional adenomas during 18-20 years of follow-up. Smoking, body mass index, alcohol intake, family history of CRC, and height were associated with higher risk of SPs and conventional adenomas, whereas higher intake of vitamin D and marine omega-3 fatty acid were associated with lower risk. The associations tended to be stronger for synchronous SPs and conventional adenomas. Smoking, body mass index, and alcohol intake were more strongly associated with SPs than conventional adenomas (P for heterogeneity <.05), whereas physical activity and intake of total folate and calcium were inversely associated with conventional adenomas but not SPs. For SPs and conventional adenomas, the associations tended to be stronger for polyps in the distal colon and rectum, of 10 mm or larger or with advanced histology.

Conclusions: In an analysis of data from 3 large prospective studies, we found that although SPs and conventional adenomas share many risk factors, some factors are more strongly associated with one type of lesion than the other. These findings provide support for the etiologic heterogeneity of colorectal neoplasia.