Genetic association studies in digestive system malignancies

The multifactorial process of carcinogenesis in the digestive system involves mutations in oncogenes or tumor suppressor genes, as well as influence of environmental etiological factors. In recent years, common DNA polymorphisms in low penetrance genes emerged as genetic factors that seem to modulate an individual's susceptibility to malignancy, through interaction with environmental factors, such as diet or smoking. The increasing number of publications of genetic association studies on digestive system neoplasias has produced both important true association results and negative or controversial results. Here, we review the findings of genetic association studies of gene polymorphisms in regard to cancers of the digestive tract (oral, esophageal, nasopharyngeal, gastric and colorectal). We discuss the association of several DNA polymorphisms in genes of cytokines, matrix metalloproteinases, signal transduction proteins, diet-, and coagulation-related factors with specific types of cancer in the digestive tract. Genetic studies, which lead to a true association, are expected to increase understanding of the pathogenesis of each malignancy and to be a powerful tool of prevention and prognosis in the future.