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Paul Brennan, James McKay, Lee Moore, David Zaridze, Anush Mukeria, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Wong-Ho Chow, Nathaniel Rothman, Amélie Chabrier, Valérie Gaborieau, Nic Timpson, Rayjean J Hung, George Davey Smith, Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype, International Journal of Epidemiology, Volume 38, Issue 4, August 2009, Pages 971–975, https://doi.org/10.1093/ije/dyp162
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Abstract
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.