BACKGROUND: Obesity is a risk factor for several cancers although appears to have an inverse association with cancers strongly related to tobacco. Studying obesity is difficult due to numerous biases and confounding. METHODS: To avoid these biases we used a Mendelian randomization approach incorporating an analysis of variants in the FTO gene that are strongly associated with BMI levels among 7000 subjects from a study of lung, kidney and upper-aerodigestive cancer. RESULTS: The FTO A allele which is linked with increased BMI was associated with a decreased risk of lung cancer (allelic odds ratio (OR) = 0.92, 95% confidence interval (CI) 0.84-1.00). It was also associated with a weak increased risk of kidney cancer, which was more apparent before the age of 50 (OR = 1.44, CI 1.09-1.90). CONCLUSION: Our results highlight the potential for genetic variation to act as an unconfounded marker of environmentally modifiable factors, and offer the potential to obtain estimates of the causal effect of obesity. However, far larger sample sizes than studied here will be required to undertake this with precision.
BACKGROUND:Obesity is a risk factor for several cancers although appears to have an inverse association with cancers strongly related to tobacco. Studying obesity is difficult due to numerous biases and confounding. METHODS: To avoid these biases we used a Mendelian randomization approach incorporating an analysis of variants in the FTO gene that are strongly associated with BMI levels among 7000 subjects from a study of lung, kidney and upper-aerodigestive cancer. RESULTS: The FTO A allele which is linked with increased BMI was associated with a decreased risk of lung cancer (allelic odds ratio (OR) = 0.92, 95% confidence interval (CI) 0.84-1.00). It was also associated with a weak increased risk of kidney cancer, which was more apparent before the age of 50 (OR = 1.44, CI 1.09-1.90). CONCLUSION: Our results highlight the potential for genetic variation to act as an unconfounded marker of environmentally modifiable factors, and offer the potential to obtain estimates of the causal effect of obesity. However, far larger sample sizes than studied here will be required to undertake this with precision.
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Authors: Xiang Shu; Mark P Purdue; Yuanqing Ye; Huakang Tu; Christopher G Wood; Nizar M Tannir; Zhaoming Wang; Demetrius Albanes; Susan M Gapstur; Victoria L Stevens; Nathaniel Rothman; Stephen J Chanock; Xifeng Wu Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-06-16 Impact factor: 4.254
Authors: Mark M Iles; Matthew H Law; Simon N Stacey; Jiali Han; Shenying Fang; Ruth Pfeiffer; Mark Harland; Stuart Macgregor; John C Taylor; Katja K Aben; Lars A Akslen; Marie-Françoise Avril; Esther Azizi; Bert Bakker; Kristrun R Benediktsdottir; Wilma Bergman; Giovanna Bianchi Scarrà; Kevin M Brown; Donato Calista; Valérie Chaudru; Maria Concetta Fargnoli; Anne E Cust; Florence Demenais; Anne C de Waal; Tadeusz Dębniak; David E Elder; Eitan Friedman; Pilar Galan; Paola Ghiorzo; Elizabeth M Gillanders; Alisa M Goldstein; Nelleke A Gruis; Johan Hansson; Per Helsing; Marko Hočevar; Veronica Höiom; John L Hopper; Christian Ingvar; Marjolein Janssen; Mark A Jenkins; Peter A Kanetsky; Lambertus A Kiemeney; Julie Lang; G Mark Lathrop; Sancy Leachman; Jeffrey E Lee; Jan Lubiński; Rona M Mackie; Graham J Mann; Nicholas G Martin; Jose I Mayordomo; Anders Molven; Suzanne Mulder; Eduardo Nagore; Srdjan Novaković; Ichiro Okamoto; Jon H Olafsson; Håkan Olsson; Hubert Pehamberger; Ketty Peris; Maria Pilar Grasa; Dolores Planelles; Susana Puig; Joan Anton Puig-Butille; Juliette Randerson-Moor; Celia Requena; Licia Rivoltini; Monica Rodolfo; Mario Santinami; Bardur Sigurgeirsson; Helen Snowden; Fengju Song; Patrick Sulem; Kristin Thorisdottir; Rainer Tuominen; Patricia Van Belle; Nienke van der Stoep; Michelle M van Rossum; Qingyi Wei; Judith Wendt; Diana Zelenika; Mingfeng Zhang; Maria Teresa Landi; Gudmar Thorleifsson; D Timothy Bishop; Christopher I Amos; Nicholas K Hayward; Kari Stefansson; Julia A Newton Bishop; Jennifer H Barrett Journal: Nat Genet Date: 2013-03-03 Impact factor: 38.330
Authors: John R B Perry; Michael N Weedon; Claudia Langenberg; Anne U Jackson; Valeriya Lyssenko; Thomas Sparsø; Gudmar Thorleifsson; Harald Grallert; Luigi Ferrucci; Marcello Maggio; Giuseppe Paolisso; Mark Walker; Colin N A Palmer; Felicity Payne; Elizabeth Young; Christian Herder; Narisu Narisu; Mario A Morken; Lori L Bonnycastle; Katharine R Owen; Beverley Shields; Beatrice Knight; Amanda Bennett; Christopher J Groves; Aimo Ruokonen; Marjo Riitta Jarvelin; Ewan Pearson; Laura Pascoe; Ele Ferrannini; Stefan R Bornstein; Heather M Stringham; Laura J Scott; Johanna Kuusisto; Peter Nilsson; Malin Neptin; Anette P Gjesing; Charlotta Pisinger; Torsten Lauritzen; Annelli Sandbaek; Mike Sampson; Ele Zeggini; Cecilia M Lindgren; Valgerdur Steinthorsdottir; Unnur Thorsteinsdottir; Torben Hansen; Peter Schwarz; Thomas Illig; Markku Laakso; Kari Stefansson; Andrew D Morris; Leif Groop; Oluf Pedersen; Michael Boehnke; Inês Barroso; Nicholas J Wareham; Andrew T Hattersley; Mark I McCarthy; Timothy M Frayling Journal: Hum Mol Genet Date: 2009-11-18 Impact factor: 6.150