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.