MTHFR POLYMORPHISMS IN PANCREATIC CANCER IN SF BAY AREA

DNA修复的能力对于维持遗传完整性和正常细胞功能以及控制异常细胞生长至关重要。叶酸是DNA修复机制所需的寡核苷酸生物合成所必需的，叶酸不足与人类癌症有关。亚甲基四氢叶酸还原酶（MTHFR）在叶酸和甲硫氨酸代谢的调节中至关重要。由于叶酸在DNA合成，修复和甲基化中很重要，它可能在癌症预防中发挥作用，最近的证据表明情况就是这样。本研究的总体目标是确定MTHTR基因中C677 T和A1298 C多态性的患病率在胰腺癌患者和对照受试者之间是否存在差异。将对334例病例和966例对照参与者的DNA进行检查，这些参与者在包括550名胰腺癌患者和1600名对照的大型基于人群的病例对照研究中抽血。所有的基因检测将使用UCSF综合癌症中心基因组核心设施和实验室人员进行。大型研究访谈中收集的变量和MTHFR遗传成分的数据分析也将在大型研究访谈中完成，MTHFR遗传成分的数据分析也将在拟议工作中完成。具体目标是：1）鉴定并比较MTHFR C677 T和A1298 C多态性在胰腺癌患者和对照受试者中的发生率; 2）评估MTHFR多态性与也可能与胰腺癌风险相关的其他暴露（如膳食叶酸、吸烟和饮酒）之间的关系;以及3）对其他膳食因素和在母研究中收集的其他数据进行分析。将使用分层和多元逻辑回归分析所有可能混淆或改变MTHFR多态性与胰腺癌之间关联的风险因素，如膳食叶酸、吸烟和饮酒。还将分析来自其他风险因素的数据。虽然低血清叶酸和胰腺癌风险之间的关系已经报道，但没有数据描述胰腺癌患者和对照受试者中MTHFR基因的多态性。这些基于问卷调查和遗传学的分析将为这种毁灭性疾病的公共卫生重要性提供新的和挑衅性的数据。

The capacity for DNA repair is essential to maintain both genetic integrity and normal cellular function and to control abnormal cell growth. Folate is required for biosynthesis of oligonucleotides needed for DNA repair mechanisms and inadequate folate has been associated with human cancer. The methylenetetrahydrofolate reductase (MTHFR) enzyme is critical in the regulation of folate and methionine metabolism. Because folate is important in DNA synthesis, repair and methylation, it may play a role in cancer prevention and recent evidence suggests that this is the case. The overall goal of this study is to determine whether the prevalence of the C677T and A1298C polymorphisms in the MTHTR gene differs between pancreatic cancer patients and control subjects. DNA will be examined from 334 cases and 966 control participants who had blood drawn in the large population-based case-control study that included 550 pancreatic cancer patients and 1600 controls. All genetic testing will be done using the UCSF Comprehensive Cancer Center Genome Core facilities and laboratory personnel. Data analyses for the variables collected in the interviews in the large study and for the MTHFR genetic component also will be completed variables collected in the interviews in the large study and for the MTHFR genetic component also will be completed under the proposed work. The specific aims are to: 1) identify and compare the incidence of MTHFR C677T and A1298C polymorphisms in pancreatic cancer patients and control subjects; 2) evaluate the relationships between MTHFR polymorphisms and other exposures that also may be related to risk for pancreatic cancer such as dietary folate, smoking and alcohol consumption; and 3) perform analyses of other dietary factors and other data collected in the parent study. Data will be analyzed using stratification and multiple logistic regression for all risk factors that could potentially confound or modify the association between the MTHFR polymorphisms and pancreatic cancer such as dietary folate, smoking and alcohol consumption. Data from other risk factors also will be analyzed. While a relationship between low serum folate and risk for pancreatic has been reported there is no data to describe polymorphisms in MTHFR genes among pancreatic cancer patients and control subjects. These questionnaire- and genetics-based analyses will provide new and provocative data of public health importance for this devastating disease.