Familial Cancers Associated With Cancers of the Breast, Prostate, Colorectum, and Lung in Sweden

Available epidemiological evidence shows that many cancers share familial risks, and this is increasingly confirmed by data on shared pathogenic germline gene variants between cancers. We decided to harness the world's largest resource on familial cancer to assess discordant familial risks for female breast (BC), prostate (PC), colorectal (CRC), and lung (LC) cancers with any of 22 different cancers in first-degree relatives (proband cancers). Familial relative risk was calculated as standardized incidence ratio (SIR) when either one proband or 2 or more (2+) probands were found in a family to distinguish low- and high-risk associations. Discordant familial associations of BC were significant for 12 1-proband and 5 2+ proband cancers. For PC, the numbers were 11 and 4; for CRC, they were 8 and 4; and for LC, they were 15 and 5. The results with large case numbers showed that BC, CRC, and LC associated with each other, but the familial association between PC and LC was negative. Many known or novel associations with possible genetic causes were found, including lobular BC with stomach cancer, PC with kidney cancer, CRC with squamous cell skin and thyroid cancers, and LC with gallbladder and endocrine tumors, the most common of which were parathyroid adenomas. Also, LC associations with esophageal and cervical cancers were unlikely to be due to smoking alone and require additional explanations. In conclusion, 2/3 of discordant associations could suggest low-risk genetic and environmental causation and 1/3 high-risk genetic causation, both waiting for experimental proof.