Dietary intake and microsatellite instability in colon tumors

Abstract

Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. Other than relatively rare mutations in mismatch repair genes, the causes of MSI are not generally known. The purpose of this study was to determine if dietary intake of nutrients previously reported as being associated with colon cancer relate specifically to the MSI disease pathway. Data from a population-based case-control study of adenocarcinoma of the colon were used to evaluate associations between dietary intake and MSI. Participants were between 30 and 79 years of age at time of diagnosis and included both men and women. Dietary intake data were obtained from a computerized diet history questionnaire. MSI was evaluated in several ways: by a panel of 10 tetranucleotide repeats, and by 2 mononucleotide repeats, BAT-26 and TGF␤RII. A total of 1,510 cases had valid study data and tumor DNA on which we were able to obtain MSI status. Cases with and without MSI were compared with dietary data reported by 2,410 population-based controls to determine dietary associations that may be different for these 2 subsets of cases. We compared dietary intake for cases with and without MSI to further determine associations that are specific to the MSI disease pathway. Key words: colon cancer; diet; microsatellite instability; alcohol; cigarette smokingDiet has been repeatedly implicated in the etiology of colon cancer. 1,2 Inconsistencies in observed associations across studies could stem from individual dietary components being associated with certain types of tumors and disease pathways, but not with colon cancer overall. Ability to examine diet in relationship to specific disease end points, as determined by specific mutations in tumors, should enhance our understanding of the disease process and the role of diet in that process.Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. 3,4 People with inherited mutations of mismatch repair genes develop MSI in colon tumors; causes of MSI in sporadic colon tumors are largely unknown. 5 In our previous evaluation of lifestyle factors associated with MSI we found that cigarette smoking is specifically associated with MSI tumors, whereas other factors such as physical activity, body size, and use of aspirin and non-steroidal anti-inflammatory drugs appear to be related equally to MSIϩ and MSIϪ tumors. 6 Although dietary factors, to our knowledge, have not been examined with MSI in tumors, it is reasonable to hypothesize that components of diet, especially those that may be influenced by cigarette smoking, could influence development of unstable tumors. Alcohol could lead to unstable tumors independently or in combination with cigarette smoking. 7 Dietary antioxidants may decrease risk of unstable tumors through their role in reducing oxygen free radicals generated by cigarette smoke. 8 Other dietary factors hypothesized to influence cell growth and apoptosis, such as calcium, vitamin D and glycemic index, could be hypothesized as being associated with MSI in tumors. 9 In this ...

Differing DNA Methylation Patterns and Gene Mutation Frequencies in Colorectal Carcinomas from Middle Eastern Countries

“…Ras proto-oncogene mutation in colorectal adenomas has been associated with low dietary folate (14), although the relationship was less clear in patients with colorectal carcinoma (15). MSI in colonic cancers has been linked to cigarette smoking and alcohol consumption (13,18) and p53 mutation in colorectal carcinoma was reported to be associated with a Western diet (13,16,17) but not cigarette smoking (13). Because the prevalences of the molecular pathways for colorectal carcinoma are different among the three Middle Eastern countries we studied, we speculate that unique environmental exposures or lifestyle factors in the Middle East may interact with genetic factors and be reflected in the differing molecular pathways.…”

“…Western diet characterized by high calories, fat, refined carbohydrates, and animal proteins is associated with p53 mutation and overexpression of the gene product (13,16,17). Cigarette smoking and alcohol consumption are related to MSI (18) and chronic inflammatory bowel disease is related to aberrant methylation (19).…”

Effects of dietary intake and genetic factors on hypermethylation of thehMLH1gene promoter in gastric cancer

“…Although it is unclear whether smoking induces hypermethylation of the hMLH1 gene promoter in humans, recent reports indicate an association between DNA methylation and tobacco carcinogens in animal models [39,40] . Previous studies have also shown that smoking and alcohol consumption increase the risk of developing microsatellite-unstable tumors [41,42] . The exact mechanism of DNA hypermethylation by alcohol is unknown.…”

Meat and meat‐mutagen intake, doneness preference and the risk of colorectal polyps: The Tennessee colorectal polyp study

“…[43][44][45][46] In a study of 276 colon cancer cases, patients with MSI colon cancers had significantly higher preference for well-done red meat and high frequencies of using certain cooking methods, such as frying, barbecuing, broiling and using meat drippings compared with MSS colon cancer patients. 46 Few studies have compared risk factors between adenomatous and hyperplastic polyps.…”