Dietary factors and truncating APC mutations in sporadic colorectal adenomas.
Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control study of sporadic colorectal adenomas (278 cases; 414 polyp-free controls). Direct-sequencing was used to screen adenomas for mutations in the mutation cluster region of APC; truncating mutations were detected in 161 (58%) of the adenomas. Red meat consumption was significantly differently related to polyps with truncating APC mutation (APC(+) polyps) compared to polyps without truncating APC mutation (APC(-) polyps) (highest vs. lowest tertile, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.3-1.0). High intake of red meat and fat seemed to increase the risk of APC(-) polyps only (APC(+) vs. controls: red meat, OR = 1.0, 95% CI = 0.6-1.6; fat, OR = 1.1, 95% CI = 0.6-1.9; APC(-) vs. controls: red meat, OR = 1.8, 95% CI = 1.0-3.1; fat, OR = 1.9, 95% CI = 1.0-3.7). Intake of carbohydrates was inversely associated with both polyp groups, most noticeably with APC(-) polyps. Most other evaluated dietary factors were not distinctively associated with a specific APC status. None of the dietary factors was specifically associated with a particular type of truncating APC mutation. Our data suggest that red meat and fat may increase the risk of APC(-) polyps in particular, whereas carbohydrates may especially decrease the risk of APC(-) polyps. However, most examined dietary factors do not appear to be specifically associated with the occurrence of truncating APC mutations in colorectal adenomas but seem to affect both pathways equally.
Diergaarde
Brenda
B
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands.
Tiemersma
Edine W
EW
Braam
Hanneke
H
van Muijen
Goos N P
GN
Nagengast
Fokko M
FM
Kok
Frans J
FJ
Kampman
Ellen
E
D000236:Adenoma / Q000209:etiology* / Q000235:genetics; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage; D002136:Calcium, Dietary / Q000008:administration & dosage; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D003611:Dairy Products; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004043:Dietary Fiber / Q000008:administration & dosage; D004044:Dietary Proteins / Q000008:administration & dosage; D002523:Edible Grain; D002149:Energy Intake; D005247:Feeding Behavior; D005260:Female; D005399:Fishes; D005492:Folic Acid / Q000008:administration & dosage; D005638:Fruit; D017491:Genes, APC; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D011200:Poultry; D017422:Sequence Analysis, DNA; D014675:Vegetables; D019207:beta Carotene / Q000008:administration & dosage
D002136:Calcium, Dietary; D004273:DNA, Neoplasm; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004043:Dietary Fiber; D004044:Dietary Proteins; D019207:beta Carotene; D005492:Folic Acid; D001205:Ascorbic Acid