Obesity and cancer: Mendelian randomization approach utilizing the FTO genotype.
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.
Brennan
Paul
P
International Agency for Research on Cancer (IARC), Genetic Epidemiology Group, Lyon, France. brennan@iarc.fr
McKay
James
J
Moore
Lee
L
Zaridze
David
D
Mukeria
Anush
A
Szeszenia-Dabrowska
Neonilia
N
Lissowska
Jolanta
J
Rudnai
Peter
P
Fabianova
Eleonora
E
Mates
Dana
D
Bencko
Vladimir
V
Foretova
Lenka
L
Janout
Vladimir
V
Chow
Wong-Ho
WH
Rothman
Nathaniel
N
Chabrier
Amélie
A
Gaborieau
Valérie
V
Timpson
Nic
N
Hung
Rayjean J
RJ
Smith
George Davey
GD
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
D005819:Genetic Markers; D009363:Neoplasm Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human