Pancreatic cancer risk and prevention: Association with PPARG gene and policy analysis of tobacco-related pancreatic cancer

This study involved a genetic association analysis of variants in the peroxisome proliferator-activated receptor-gamma gene and pancreatic cancer risk, and a policy analysis of tobacco-related pancreatic cancer.;A nested case-control study was conducted in 83 incident cases of pancreatic cancer and 166 matched controls originally recruited into the Beta Carotene and Retinol Efficacy Trial. All subjects were smokers. Associations between PPARG tagging single nucleotide polymorphisms (tagSNPs) and haplotypes and pancreatic cancer risk were measured using conditional logistic regression. Carriers of the G allele (coding for Ala) of the Pro12Ala variant had an odds ratio (OR) of 1.79 (95% confidence interval (CI): 0. 96--3.33, p=0.06) compared to homozygous carriers of the C allele (Pro). Among subjects randomized to high-dose vitamin A, the OR was 2.80 (95% CI: 1.16--6.74, p=0.02) compared to 1.20 (95% CI: 0.45--3.23, p=0.71) in the placebo group. Three other tagSNPs at the 5' end of PPARG were also borderline significantly associated with pancreatic cancer risk. A haplotype including the Pro12Ala variant G allele (coding for Ala) was associated with an OR of 2.10 (95% Cl: 1.08--4.11, p=0.03). Among subjects randomized to high-dose vitamin A, the OR increased to 3.32 (95% CI: 1.27--8.66, p=0.01).;A policy framework was used to propose and evaluate policy options to address the issue that tobacco use causes pancreatic cancer. A literature review was conducted to summarize the evidence that smokeless tobacco (SLT) increases pancreatic cancer risk, because SLT is frequently cited as a reduced harm alternative to cigarettes. Policy options included strategies to investigate and regulate tobacco-specific nitrosamines (TSNAs), which may cause pancreatic cancer.;Because two published studies found that low-TSNA Swedish snus could increase pancreatic cancer risk, we recommended that federal funding of tobacco harm reduction research begin immediately to establish the carcinogenic effect of TSNAs on the pancreas.;This analysis presents the first evidence that the PPARG Pro12Ala variant may be associated with pancreatic cancer risk. This risk may be limited to smokers exposed to high levels of vitamin A. We also established that pancreatic cancer risk should be considered in tobacco harm reduction policies.