Research list


Studies of a genetic polymorphism support the role of bile acids in colorectal carcinogenesis

High-fat diet has long been implicated in the etiology of colorectal cancer. Increased production of bile acids is one of the postulated mechanisms underlying the fat hypothesis. However, studies of individuals like case-control and cohort studies have failed to confirm the fat hypothesis in colorectal carcinogenesis. A study group lead by Professor Suminori Kono, Department of Preventive Medicine, Kyushu University, addressed the role of bile acids in colorectal carcinogenesis, by investigating a genetic polymorphism (-203A>C) of CYP7A1, which is the rate-limiting enzyme in the process of producing bile acids. In a case-control study of 685 cases of colorectal cancer and 778 community controls, which Professor Kono named the Fukuoka Colorectal Cancer Study, they found no overall association between the CYP7A1 genetic polymorphism and colorectal cancer, but observed that the homozygous variant of CC genotype had a decreased risk of right-sided colon cancer.
Professor Kono and his colleagues also studied the genetic polymorphism of CYP7A1 in a case control study of 446 cases of colorectal adenoma and 914 controls of normal colonoscopy. Adenoma is a well-established precursor lesion of colorectal cancer. Again, there was no overall association between the CYP7A1 polymorphism and colorectal adenoma, but the homozygous variant of CC genotype was associated with an evident decrease in the risk of right-sided colon adenoma.
Professor Kono said, “Our findings are just a small piece of information in thinking of the fat and colon cancer story, but the remarkable consistency in two studies is a pleasant surprise.” He also added,“Epidemiology using genetic information is very useful for understanding the influence of lifestyle factors in the occurrence of cancer and other diseases.”