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

机译：胰腺癌的风险和预防：与PPARG基因的关联以及与烟草有关的胰腺癌的政策分析。

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摘要

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.
机译：这项研究涉及过氧化物酶体增殖物激活的受体-γ基因变异与胰腺癌风险的遗传关联分析，以及与烟草有关的胰腺癌的政策分析。；对83例胰腺癌病例进行了巢式病例对照研究。癌症和166个匹配的对照组最初招募进入β-胡萝卜素和视黄醇功效试验。所有受试者均为吸烟者。使用条件对数回归测量PPARG标签单核苷酸多态性（tagSNPs）与单倍型和胰腺癌风险之间的关联。与C的纯合子相比，Pro12Ala变体的G等位基因（编码Ala）的携带者的比值比（OR）为1.79（95％置信区间（CI）：0.96--3.33，p = 0.06）等位基因（Pro）。在随机分配给高剂量维生素A的受试者中，OR为2.80（95％CI：1.16--6.74，p = 0.02），而安慰剂组为1.20（95％CI：0.45--3.23，p = 0.71）。 PPARG 5'末端的其他三个tagSNPs也与胰腺癌风险显着相关。包括Pro12Ala变体G等位基因（编码Ala）的单倍型与OR为2.10（95％Cl：1.08--4.11，p = 0.03）相关。在随机分配给高剂量维生素A的受试者中，OR增至3.32（95％CI：1.27--8.66，p = 0.01）.;使用了政策框架来提出和评估政策选择，以解决烟草使用引起的问题胰腺癌。进行了文献综述以总结无烟烟草（SLT）增加胰腺癌风险的证据，因为无烟烟草经常被认为是替代卷烟的减少危害的替代品。政策选择包括研究和调节可能引起胰腺癌的烟草特有亚硝胺（TSNA）的策略；由于两项已发表的研究发现低TSNA瑞典鼻烟可能会增加胰腺癌的风险，因此我们建议联邦政府资助减少烟草危害研究的研究开始立即建立TSNAs对胰腺癌的作用。；该分析提供了第一个证据，表明PPARG Pro12Ala变体可能与胰腺癌风险相关。这种风险可能仅限于暴露于高水平维生素A的吸烟者。我们还确定，在减少烟草危害的政策中应考虑胰腺癌的风险。

著录项

  • 作者

    Fesinmeyer, Megan Dann.;

  • 作者单位

    University of Washington.;

  • 授予单位 University of Washington.;
  • 学科 Public health.;Genetics.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 64 p.
  • 总页数 64
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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