Establishing a valid approach for estimating familial risk of cancer explained by common genetic variants

• Verfasst von: Weigl, Korbinian [VerfasserIn]
• Verfasst von: Chang-Claude, Jenny [VerfasserIn]
• Verfasst von: Hoffmeister, Michael [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Titel: Establishing a valid approach for estimating familial risk of cancer explained by common genetic variants
• Verf.angabe: Korbinian Weigl, Jenny Chang‐Claude, Li Hsu, Michael Hoffmeister and Hermann Brenner
• Jahr: 2020
• Jahr des Originals: 2019
• Umfang: 8 S.
• Teil: volume:146
• Teil: year:2020
• Teil: number:1
• Teil: pages:68-75
• Teil: extent:8
• Fussnoten: Gesehen am 06.04.2020 ; First published: 04 September 2019
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2020
• Band/Heft Quelle: 146(2020), 1, Seite 68-75
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.32664
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: common genetic variants
• Sach-SW: excess risk
• Sach-SW: familial risk
• Sach-SW: genetic epidemiology
• Sach-SW: risk proportion
• K10plus-PPN: 1694144259

Abstract

We critically examined existing approaches for the estimation of the excess familial risk of cancer that can be attributed to identified common genetic risk variants and propose an alternative, more straightforward approach for calculating this proportion using well-established epidemiological methodology. We applied the underlying equations of the traditional approaches and the new epidemiological approach for colorectal cancer (CRC) in a large population-based case-control study in Germany with 4,447 cases and 3,480 controls, who were recruited from 2003 to 2016 and for whom interview, medical and genomic data were available. Having a family history of CRC (FH) was associated with a 1.77-fold risk increase in our study population (95% CI 1.52-2.07). Traditional approaches yielded estimates of the FH-associated risk explained by 97 common genetics variants from 9.6% to 23.1%, depending on various assumptions. Our alternative approach resulted in smaller and more consistent estimates of this proportion, ranging from 5.4% to 14.3%. Commonly employed methods may lead to strongly divergent and possibly exaggerated estimates of excess familial risk of cancer explained by associated known common genetic variants. Our results suggest that familial risk and risk associated with known common genetic variants might reflect two complementary major sources of risk.