Carcinogenesis, Vol. 24, No. 2, 283-290,
February 2003
© 2003 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Dietary factors and the occurrence of truncating APC mutations in sporadic colon carcinomas: a Dutch population-based study
1 Division of Human Nutrition and Epidemiology, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands and
2 Department of Pathology, UMC St Radboud, Nijmegen, The Netherlands
The interactions between environmental factors and the genetic and epigenetic changes that drive colon carcinogenesis are not clear. Dietary factors reported previously to be associated with colon cancer risk may well influence the occurrence of specific somatic alterations in colon tumors. To explore this idea, data from a Dutch population-based case-control study (184 cases, 259 controls) on sporadic colon cancer were used to assess associations between dietary factors and the occurrence of truncating mutations in the adenomatous polyposis coli (APC) gene in carcinomas. Single-strand conformation polymorphism analysis and DNA sequencing were used to screen tumors for mutations in the mutation cluster region of APC. Usual dietary habits were assessed by an interview-based questionnaire. Truncating APC mutations were detected in 63 (34%) of the tumors. Vegetable consumption was inversely associated with APC+ (with mutation) tumors [odds ratio (OR) and 95% confidence interval (CI) for highest versus lowest tertile, OR: 0.6, 95% CI: 0.3–1.3] as well as APC- (without mutation) tumors (OR: 0.3, 95% CI: 0.2–0.5). Alcohol intake was positively associated with APC- tumors (OR: 1.7, 95% CI: 1.0–3.0) and inversely associated with APC+ tumors (OR: 0.5, 95% CI: 0.3–1.1). Positive associations were observed for meat, fish and fat with APC+ tumors (OR: 1.7, 95% CI: 0.8–3.6; OR: 1.4, 95% CI: 0.7–2.8; OR: 4.5, 95% CI: 1.6–12.8, respectively). Of the dietary factors examined, vegetable consumption and alcohol intake were significantly different related to APC+ tumors than to APC- tumors (APC+ versus APC-, OR: 2.3, 95% CI: 1.0–5.3; OR: 0.3, 95% CI: 0.2–0.7, respectively). Our data suggest that vegetables play a protective role in the etiology of both tumor subsets, although this role appears to be less influential in the APC+ group. Alcohol seems to especially promote the development of APC- tumors whereas meat, fish and fat appear to enhance the development of APC+ tumors.
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