Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype

• Published in: International journal of epidemiology Vol. 38; no. 4; pp. 971 - 975
• Main Authors: Brennan, Paul, McKay, James, Moore, Lee, Zaridze, David, Mukeria, Anush, Szeszenia-Dabrowska, Neonilia, Lissowska, Jolanta, Rudnai, Peter, Fabianova, Eleonora, Mates, Dana, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Chow, Wong-Ho, Rothman, Nathaniel, Chabrier, Amélie, Gaborieau, Valérie, Timpson, Nic, Hung, Rayjean J, Smith, George Davey
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2009; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Body Mass Index; Cancer; Europe - epidemiology; Female; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Genotype; Head and Neck Neoplasms - epidemiology; Head and Neck Neoplasms - etiology; Head and Neck Neoplasms - genetics; Humans; Kidney Neoplasms - epidemiology; Kidney Neoplasms - etiology; Kidney Neoplasms - genetics; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Male; Mendelian randomization; Middle Aged; Neoplasm Proteins - genetics; Neoplasms - epidemiology; Neoplasms - etiology; Neoplasms - genetics; Obesity; Obesity - complications; Obesity - epidemiology; Obesity - genetics; Proteins - genetics; Risk Factors; Obesity; cancer; Mendelian randomization
• ISSN: 0300-5771; 1464-3685; 1464-3685
• DOI: 10.1093/ije/dyp162

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.