title: Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype.
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).
  
  
  CONCLUSIONS
  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.
authors: International Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France. brennan@iarc.fr
authors: Paul
authors: P
authors: Brennan
authors: James
authors: J
authors: McKay
authors: Lee
authors: L
authors: Moore
authors: David
authors: D
authors: Zaridze
authors: Anush
authors: A
authors: Mukeria
authors: Neonilia
authors: N
authors: Szeszenia-Dabrowska
authors: Jolanta
authors: J
authors: Lissowska
authors: Peter
authors: P
authors: Rudnai
authors: Eleonora
authors: E
authors: Fabianova
authors: Dana
authors: D
authors: Mates
authors: Vladimir
authors: V
authors: Bencko
authors: Lenka
authors: L
authors: Foretova
authors: Vladimir
authors: V
authors: Janout
authors: Wong-Ho
authors: WH
authors: Chow
authors: Nathaniel
authors: N
authors: Rothman
authors: Amélie
authors: A
authors: Chabrier
authors: Valérie
authors: V
authors: Gaborieau
authors: Nic
authors: N
authors: Timpson
authors: Rayjean J
authors: RJ
authors: Hung
authors: George Davey
authors: GD
authors: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D005060:Europe / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D009765:Obesity / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D009363:Neoplasm Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human