Population Landscape of Familial Cancer

Scientific Report - Nature - open access


.... Our study showed that the existence of affected family members is an important risk factor for all cancer types. For common cancers familial risk even increased with the number of affected family members. Until now, over 100 cancer predisposing variants have been identified and in addition over 300 low-risk loci have been mapped¹⁵. However, only a small proportion of familial cancer can be explained by the established genetic predisposition, and the proposed risk estimates vary extensively¹⁶. For example, in colorectal cancer some studies have assumed that mismatch repair gene defects (hereditary non-polyposis colon cancer) account for most of familial aggregation¹⁷, but the recent exome sequencing data put the figure at 11% of familial cancer and early onset cases¹⁸. In clinical genetic counseling mutation testing is offered only for a few high-risk cancer predisposing genes.......

..... Furthermore, high-risk cancer predisposing genes such as BRCA1/BRCA2 associated with familial breast cancer or mismatch repair genes involved in Lynch syndrome (hereditary non-polyposis colon cancer) may account for significantly increased risk of breast and colorectal cancers in the cluster of affected parents and siblings. Interestingly, the corresponding risks for two affected siblings were also elevated, but only modestly and the difference was significant only for breast cancer......


 In conclusion, our results show that familial risk is a shared feature of all cancers and for many cancers multiple affected family members signal a high or very high risk that would necessarily require medical action. Some of such families are likely carriers of known high-risk cancer predisposition genes. However, the major proportion of familial cluster is probably caused by genes that remain to be discovered. Nevertheless, medical or behavioral intervention may be indicated, including screening recommendations or avoidance of carcinogenic exposures. The readily available information of family history deserves more attention in the first oncology contacts and established referral mechanisms for clinical counseling to evaluate screening and prevention strategies individually tailored to patients and their family members.