This case–control study of 310 colorectal cancer cases and 1177 controls in a nested prospective, population-based cohort of Singapore Chinese subjects found a statistically significant association between the cyclooxygenase (COX)-2 −765G>C gene polymorphism and colon cancer risk among high consumers of dietary n-6 polyunsaturated fatty acids (odds ratio=2.38, 95% confidence interval=1.23–4.59). This evidence concerns the gene PTGS2 and colorectal cancer.