Associations between Folate and Alcohol Consumption with Colorectal Tumor Ki67 Expression in the Southern Community...

Folate is hypothesized to accelerate cell proliferation in colorectal cancer (CRC) by supporting DNA synthesis, while alcohol is also linked to gastrointestinal epithelial proliferation, despite biological antagonism of folate. We report associations between folate and alcohol consumption with the proliferation marker Ki67 in CRC tumors from the Southern Community Cohort Study. Tumor samples were obtained from formalin-fixed paraffin-embedded tissue blocks. The percentage of cells expressing Ki67 was measured immunohistochemically. Exposures were assessed via questionnaire pre-diagnosis. Associations were assessed via linear regression. In 248 cases (40-78 years), neither dietary folate, folic acid supplements, nor total folate intake were associated with Ki67. Folic acid supplement use was associated with Ki67 in distal/rectal tumors (β [95% confidence interval]: 7.5 [1.2-13.8], p = .02) but not proximal tumors (-1.4 [-7.1-4.3], p=.62). A positive trend for total folate was observed for distal/rectal tumors (1.6 [0.0-3.3] per 200 μcg, p-trend=.05). Heavy drinking (women: ≥1 drink/day, men: ≥2 drinks/day) was associated with higher Ki67 (6.4 [1.0-11.9], vs. nondrinkers, p=.02), especially for distal/rectal tumors (10.4 [1.6-19.1], p=.02). Negative interaction between alcohol, total folate was observed for distal/rectal tumors (p-interaction=.06). Modest associations between folate, alcohol consumption and distal/rectal tumor Ki67 expression suggest accelerated proliferation, consistent with folate's role in DNA synthesis.