Family history of colon cancer: What does it mean and how is it useful? Original Research Article

Background Family history of colon cancer can be deconstructed into causal and noncausal explanations, which include genetic factors, environmental factors, gene–environment interactions, misclassification, and differences in screening. Methods We investigated some of these causal and noncausal explanations by using data from a case–control study of colon cancer conducted among African Americans and whites in North Carolina. We examined the relationship between family history and polymorphisms in four genes (N-acetyltransferase 1 and 2 [NAT1, NAT2], methylenetetrahydrofolate reductase, and peroxisome proliferator-activated receptor gamma [PPARG]), environmental risk factors, the joint distributions of these genes and environmental risk factors, and the prevalence of colon cancer screening. Results Participants with one or more first-degree relatives with colon cancer showed a slightly higher prevalence of at-risk genotypes for each locus, but results were statistically significant only for NAT2. Participants with a family history showed a higher prevalence of at-risk combinations of genotypes and environmental risk factors (NAT2 and well-done red meat consumption; PPARG and nonsteroidal anti-inflammatory medication use). The sensitivity and predictive value of family history for identifying persons with at-risk genotypes or environmental risk factors was low. History of cancer screening was similar in those with and without a family history. Conclusions Our results suggest that family history of colon cancer may represent aggregation of some genetic polymorphisms and environmental risk factors. Although it is premature to use family history as a screening tool when testing for genetic polymorphisms, further research is needed to identify additional genes and environmental factors that may be associated with family history.