Association between the peroxisome proliferator-activated receptor gamma Pro12Ala variant and haplotype and pancreatic cancer in a high-risk cohort of smokers: a pilot study.
OBJECTIVE
The Pro12Ala variant in the peroxisome proliferator-activated receptor gamma (PPARG) gene has been associated with diabetes and several cancers. This pilot study tested for the association between Pro12Ala and pancreatic cancer risk in a high-risk sample of smokers.


METHODS
A nested case-control study was conducted in 83 incident cases of pancreatic cancer and 166 matched controls originally recruited into a cohort chemoprevention study of lung cancer. Associations between Pro12Ala and pancreatic cancer risk were measured using conditional logistic regression.


RESULTS
Carriers of the G allele (Ala) of the Pro12Ala variant had a borderline increased relative risk of pancreatic cancer compared with homozygous carriers of the C allele (Pro), with an odds ratio of 1.79 (95% confidence interval [CI], 0.96-3.33; P=0.06). Among subjects randomized to high-dose vitamin A, the odds ratio was 2.80 (95% CI, 1.16-6.74; P=0.02) versus 1.20 (95% CI, 0.45-3.23; P=0.71) in the placebo group. A haplotype including Pro12Ala was also significantly associated with pancreatic cancer risk in all subjects and in subjects randomized to vitamin A.


CONCLUSIONS
This analysis presents the first evidence that PPARG may be associated with pancreatic cancer risk, and this candidate gene should be investigated in future, larger studies.
Institute for Public Health Genetics, University of Washington, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Department of Epidemiology, Seattle, WA 98195, USA.
Megan Dann
MD
Fesinmeyer
Janet L
JL
Stanford
Teresa A
TA
Brentnall
Margaret T
MT
Mandelson
Federico M
FM
Farin
Sengkeo
S
Srinouanprachanh
Zahra
Z
Afsharinejad
Gary E
GE
Goodman
Matt J
MJ
Barnett
Melissa A
MA
Austin
D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*
D047495:PPAR gamma