Although there is considerable evidence that high consumption of red meat may increase the risk of colorectal cancer, data by subsite within the colon are sparse. The objective of our study was to prospectively examine whether the association of red meat consumption with cancer risk varies by subsite within the large bowel. We analyzed data from the Swedish Mammography Cohort of 61,433 women aged 40 -75 years and free from diagnosed cancer at baseline in [1987][1988][1989][1990]. Diet was assessed at baseline using a self-administered food-frequency questionnaire. Over a mean follow-up of 13.9 years, we identified 234 proximal colon cancers, 155 distal colon cancers and 230 rectal cancers. We observed a significant positive association between red meat consumption and risk of distal colon cancer (p for trend ؍ 0.001) but not of cancers of the proximal colon (p for trend ؍ 0.95) or rectum (p for trend ؍ 0.32). The multivariate rate ratio for women who consumed 94 or more g/day of red meat compared to those who consumed less than 50 g/day was 2. Although there is mounting support in the literature of an increased risk of colon or colorectal cancer associated with high consumption of red meat, 1,2 data for subsites within the colon are limited and conflicting. [3][4][5] Multiple lines of evidence indicate that proximal and distal colon cancers may have distinct etiologies. 6 -10 Cancers arising in the proximal and distal colon exhibit differences in incidence according to geographic region, age and sex. 7,10 Furthermore, there are various molecular and clinical differences between proximal and distal sites of the colon that may influence the susceptibility to environmental factors. 10 For example, differences between subsites exist in pH, 11 bacterial composition and bacterial metabolic capacity, 12,13 apoptotic index, 14 activity of ornithine decarboxylase 15 and expression of carcinogen metabolizing enzymes. 16 These differences underscore the need for separate analyses by subsite within the colon.Components in red meat or which are formed during the cooking of meat that may increase colorectal cancer risk include animal fat, 17,18 heme iron 19 -21 and heterocyclic amines (HCAs). 22,23 In addition, human experimental studies have demonstrated that high red meat diets enhance the endogenous formation of N-nitroso compounds (NOCs), 24 -27 which have been found to induce the formation of DNA adducts in human colonocytes. 28 The concentrations of the pro-mutagenic lesion O 6 -methyldeoxyguanosine, a marker of exposure to many NOCs, have been shown to be significantly greater in tissues from the distal colon and rectum than from the proximal colon. 29 A direct association of meat consumption with body iron stores has been found in many studies. 30 -32 In a nested case-control study, an increased colorectal cancer risk associated with high serum iron levels was restricted to the distal colon and rectum. 33 Thus, given these findings, a potential effect of diets high in red meat might be limited to cancers of t...