IJE Advance Access originally published online on June 19, 2009
International Journal of Epidemiology 2009 38(4):971-975; doi:10.1093/ije/dyp162
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Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype
1 International Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France.
2 National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
3 Cancer Research Centre, Institute of Carcinogenesis, Moscow, Russia.
4 Institute of Occupational Medicine, Department of Epidemiology, Lodz, Poland.
5 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Department of Cancer Epidemiology and Prevention, Warsaw, Poland.
6 National Institute of Environmental Health, Budapest, Hungary.
7 Specialized Institute of Hygiene and Epidemiology, Banska Bystrica, Slovakia.
8 Institute of Public Health, Bucharest, Romania.
9 Charles University, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague 2, Czech Republic.
10 Mazaryk Memorial Cancer Institute, Department of Cancer Epidemiology and Genetics, Brno, Czech Republic.
11 Palacky University, Faculty of Medicine, Department of Preventive Medicine, Olomouc, Czech Republic.
12 MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE), Department of Social Medicine, Canynge Hall, Bristol, UK.
13 Samuel Lunenfeld Research Institute, Cancer Care Ontario Research Chair, University of Toronto, ON, Canada.
* Corresponding author. Dr Paul Brennan, Genetic Epidemiology Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69008 Lyon, France. E-mail: brennan{at}iarc.fr
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Abstract |
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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.
Keywords Obesity, cancer, Mendelian randomization
Accepted 18 February 2009
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