Hongyao Yu1, Christoph Frank1, Jan Sundquist2,3, Akseli Hemminki4,5, Kari Hemminki1,2. 1. Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany. 2. Center for Primary Health Care Research, Lund University, Malmö, Sweden. 3. Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA. 4. Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 5. Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
Abstract
BACKGROUND: It has been proposed that cancer is more common in some families than in others, but the hypothesis lacks population level support. We use a novel approach by studying any cancers in large three-generation families and thus are able to find risks even though penetrance is low. METHODS: Individuals in the nation-wide Swedish Family-Cancer Database were organised in three generations and the relative risk (RR) of cancer was calculated to the persons in the third generation by the numbers of patients with cancer in generations 1, 2 and 3. RESULTS: The RRs for any cancer in generation 3 increased by the numbers of affected relatives, reaching 1.61 when at least seven relatives were diagnosed. The median patient had two affected relatives, and 7.0% had five or more affected relatives with an RR of 1.46, which translated to an absolute risk of 21.5% compared with 14.7% in population by age 65 years. For prostate cancer, the RR was 2.85 with four or more affected family members with any cancer, and it increased to 14.42 with four or more concordant cancers in family members. RRs for prostate cancer were approximately equal (2.70 vs 2.85) if a man had one relative with prostate cancer or four or more relatives diagnosed with any cancer. CONCLUSIONS: A strong family history of cancer, regardless of tumour type, increases cancer risk of family members and calls for mechanistic explanations. Our data provide tools for counselling of patients with cancer with both low and high familiar risks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
BACKGROUND: It has been proposed that cancer is more common in some families than in others, but the hypothesis lacks population level support. We use a novel approach by studying any cancers in large three-generation families and thus are able to find risks even though penetrance is low. METHODS: Individuals in the nation-wide Swedish Family-Cancer Database were organised in three generations and the relative risk (RR) of cancer was calculated to the persons in the third generation by the numbers of patients with cancer in generations 1, 2 and 3. RESULTS: The RRs for any cancer in generation 3 increased by the numbers of affected relatives, reaching 1.61 when at least seven relatives were diagnosed. The median patient had two affected relatives, and 7.0% had five or more affected relatives with an RR of 1.46, which translated to an absolute risk of 21.5% compared with 14.7% in population by age 65 years. For prostate cancer, the RR was 2.85 with four or more affected family members with any cancer, and it increased to 14.42 with four or more concordant cancers in family members. RRs for prostate cancer were approximately equal (2.70 vs 2.85) if a man had one relative with prostate cancer or four or more relatives diagnosed with any cancer. CONCLUSIONS: A strong family history of cancer, regardless of tumour type, increases cancer risk of family members and calls for mechanistic explanations. Our data provide tools for counselling of patients with cancer with both low and high familiar risks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Entities:
Keywords:
Cancer susceptibility; Discordant familial cancer; Epidemiology; Familial risk; Population database
Authors: Xia Jiang; Hilary K Finucane; Fredrick R Schumacher; Stephanie L Schmit; Jonathan P Tyrer; Younghun Han; Kyriaki Michailidou; Corina Lesseur; Karoline B Kuchenbaecker; Joe Dennis; David V Conti; Graham Casey; Mia M Gaudet; Jeroen R Huyghe; Demetrius Albanes; Melinda C Aldrich; Angeline S Andrew; Irene L Andrulis; Hoda Anton-Culver; Antonis C Antoniou; Natalia N Antonenkova; Susanne M Arnold; Kristan J Aronson; Banu K Arun; Elisa V Bandera; Rosa B Barkardottir; Daniel R Barnes; Jyotsna Batra; Matthias W Beckmann; Javier Benitez; Sara Benlloch; Andrew Berchuck; Sonja I Berndt; Heike Bickeböller; Stephanie A Bien; Carl Blomqvist; Stefania Boccia; Natalia V Bogdanova; Stig E Bojesen; Manjeet K Bolla; Hiltrud Brauch; Hermann Brenner; James D Brenton; Mark N Brook; Joan Brunet; Hans Brunnström; Daniel D Buchanan; Barbara Burwinkel; Ralf Butzow; Gabriella Cadoni; Trinidad Caldés; Maria A Caligo; Ian Campbell; Peter T Campbell; Géraldine Cancel-Tassin; Lisa Cannon-Albright; Daniele Campa; Neil Caporaso; André L Carvalho; Andrew T Chan; Jenny Chang-Claude; Stephen J Chanock; Chu Chen; David C Christiani; Kathleen B M Claes; Frank Claessens; Judith Clements; J Margriet Collée; Marcia Cruz Correa; Fergus J Couch; Angela Cox; Julie M Cunningham; Cezary Cybulski; Kamila Czene; Mary B Daly; Anna deFazio; Peter Devilee; Orland Diez; Manuela Gago-Dominguez; Jenny L Donovan; Thilo Dörk; Eric J Duell; Alison M Dunning; Miriam Dwek; Diana M Eccles; Christopher K Edlund; Digna R Velez Edwards; Carolina Ellberg; D Gareth Evans; Peter A Fasching; Robert L Ferris; Triantafillos Liloglou; Jane C Figueiredo; Olivia Fletcher; Renée T Fortner; Florentia Fostira; Silvia Franceschi; Eitan Friedman; Steven J Gallinger; Patricia A Ganz; Judy Garber; José A García-Sáenz; Simon A Gayther; Graham G Giles; Andrew K Godwin; Mark S Goldberg; David E Goldgar; Ellen L Goode; Marc T Goodman; Gary Goodman; Kjell Grankvist; Mark H Greene; Henrik Gronberg; Jacek Gronwald; Pascal Guénel; Niclas Håkansson; Per Hall; Ute Hamann; Freddie C Hamdy; Robert J Hamilton; Jochen Hampe; Aage Haugen; Florian Heitz; Rolando Herrero; Peter Hillemanns; Michael Hoffmeister; Estrid Høgdall; Yun-Chul Hong; John L Hopper; Richard Houlston; Peter J Hulick; David J Hunter; David G Huntsman; Gregory Idos; Evgeny N Imyanitov; Sue Ann Ingles; Claudine Isaacs; Anna Jakubowska; Paul James; Mark A Jenkins; Mattias Johansson; Mikael Johansson; Esther M John; Amit D Joshi; Radka Kaneva; Beth Y Karlan; Linda E Kelemen; Tabea Kühl; Kay-Tee Khaw; Elza Khusnutdinova; Adam S Kibel; Lambertus A Kiemeney; Jeri Kim; Susanne K Kjaer; Julia A Knight; Manolis Kogevinas; Zsofia Kote-Jarai; Stella Koutros; Vessela N Kristensen; Jolanta Kupryjanczyk; Martin Lacko; Stephan Lam; Diether Lambrechts; Maria Teresa Landi; Philip Lazarus; Nhu D Le; Eunjung Lee; Flavio Lejbkowicz; Heinz-Josef Lenz; Goska Leslie; Davor Lessel; Jenny Lester; Douglas A Levine; Li Li; Christopher I Li; Annika Lindblom; Noralane M Lindor; Geoffrey Liu; Fotios Loupakis; Jan Lubiński; Lovise Maehle; Christiane Maier; Arto Mannermaa; Loic Le Marchand; Sara Margolin; Taymaa May; Lesley McGuffog; Alfons Meindl; Pooja Middha; Austin Miller; Roger L Milne; Robert J MacInnis; Francesmary Modugno; Marco Montagna; Victor Moreno; Kirsten B Moysich; Lorelei Mucci; Kenneth Muir; Anna Marie Mulligan; Katherine L Nathanson; David E Neal; Andrew R Ness; Susan L Neuhausen; Heli Nevanlinna; Polly A Newcomb; Lisa F Newcomb; Finn Cilius Nielsen; Liene Nikitina-Zake; Børge G Nordestgaard; Robert L Nussbaum; Kenneth Offit; Edith Olah; Ali Amin Al Olama; Olufunmilayo I Olopade; Andrew F Olshan; Håkan Olsson; Ana Osorio; Hardev Pandha; Jong Y Park; Nora Pashayan; Michael T Parsons; Tanja Pejovic; Kathryn L Penney; Wilbert H M Peters; Catherine M Phelan; Amanda I Phipps; Dijana Plaseska-Karanfilska; Miranda Pring; Darya Prokofyeva; Paolo Radice; Kari Stefansson; Susan J Ramus; Leon Raskin; Gad Rennert; Hedy S Rennert; Elizabeth J van Rensburg; Marjorie J Riggan; Harvey A Risch; Angela Risch; Monique J Roobol; Barry S Rosenstein; Mary Anne Rossing; Kim De Ruyck; Emmanouil Saloustros; Dale P Sandler; Elinor J Sawyer; Matthew B Schabath; Johanna Schleutker; Marjanka K Schmidt; V Wendy Setiawan; Hongbing Shen; Erin M Siegel; Weiva Sieh; Christian F Singer; Martha L Slattery; Karina Dalsgaard Sorensen; Melissa C Southey; Amanda B Spurdle; Janet L Stanford; Victoria L Stevens; Sebastian Stintzing; Jennifer Stone; Karin Sundfeldt; Rebecca Sutphen; Anthony J Swerdlow; Eloiza H Tajara; Catherine M Tangen; Adonina Tardon; Jack A Taylor; M Dawn Teare; Manuel R Teixeira; Mary Beth Terry; Kathryn L Terry; Stephen N Thibodeau; Mads Thomassen; Line Bjørge; Marc Tischkowitz; Amanda E Toland; Diana Torres; Paul A Townsend; Ruth C Travis; Nadine Tung; Shelley S Tworoger; Cornelia M Ulrich; Nawaid Usmani; Celine M Vachon; Els Van Nieuwenhuysen; Ana Vega; Miguel Elías Aguado-Barrera; Qin Wang; Penelope M Webb; Clarice R Weinberg; Stephanie Weinstein; Mark C Weissler; Jeffrey N Weitzel; Catharine M L West; Emily White; Alice S Whittemore; H-Erich Wichmann; Fredrik Wiklund; Robert Winqvist; Alicja Wolk; Penella Woll; Michael Woods; Anna H Wu; Xifeng Wu; Drakoulis Yannoukakos; Wei Zheng; Shanbeh Zienolddiny; Argyrios Ziogas; Kristin K Zorn; Jacqueline M Lane; Richa Saxena; Duncan Thomas; Rayjean J Hung; Brenda Diergaarde; James McKay; Ulrike Peters; Li Hsu; Montserrat García-Closas; Rosalind A Eeles; Georgia Chenevix-Trench; Paul J Brennan; Christopher A Haiman; Jacques Simard; Douglas F Easton; Stephen B Gruber; Paul D P Pharoah; Alkes L Price; Bogdan Pasaniuc; Christopher I Amos; Peter Kraft; Sara Lindström Journal: Nat Commun Date: 2019-01-25 Impact factor: 17.694