Concordant and discordant familial cancer: Familial risks, proportions and population impact. Issue 7 (20th January 2017)

• Record Type: Journal Article
• Authors: Frank, Christoph; Sundquist, Jan; Yu, Hongyao; Hemminki, Akseli; Hemminki, Kari
• Is Part Of: International journal of cancer. Volume 140:Issue 7(2017:Apr. 01)
• Page Start: 1510
• Page End: 1516
• Publication Date: 2017-01-20
• Subjects: familial cancer -- discordant cancer -- familial risk -- population impact; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30583
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown – beyond well characterized hereditary cancer syndromes ‐ but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family‐Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge. Abstract : What's new? Familial cancer risk is well‐established, particularly for cancers of the same (concordant) type. By contrast, little is known about possible risks when family members are diagnosed with multiple different (discordant) cancers. Here, using data from the Swedish Family‐Cancer Database, familial risks and population impact of concordant and discordant familial cancers were analyzed for the 27 most common malignancies. The occurrence of discordant cancers in families was found to significantly increase cancer risk, though not to the same extent as for concordant cancers. The data suggest that a general genetic susceptibility to cancer exists in some families.