Family history and the risk of cancer: genetic factors influencing multiple cancer sites

A number of co-aggregations of cancers at different sites has been reported, including recognized syndromes (e.g., Li-Fraumeni), and aggregations between cancers at breast, stomach and ovary, between cancers at prostate, urinary tract and other sites, as well as between several tobacco-related neoplasms. In a network of case-control studies from Italy and Switzerland, including more than 12,000 cases of 13 different cancers, after controlling for multiple testing, significant associations emerged between oral and pharyngeal cancer and family history of laryngeal cancer (relative risk (RR): 3.3); esophageal cancer and family history of oral and pharyngeal cancer RR: 4.1; breast cancer and family history of colorectal cancer (RR: 1.5) and of hemolymphopoietic cancers (RR: 1.7); ovarian cancer and family history of breast cancer (RR: 2.3); and prostate cancer and family history of bladder cancer (RR: 3.4). Shared exposures to environmental factors within families account for some of the observed aggregations, together with heritable, and hence, genetic factors.