MOLECULAR EPIDEMIOLOGY AND PREVENTION OF BREAST CANCER

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究将采用癌症病例对照研究设计来评估两个假设。研究受试者将包括800例新发乳腺癌病例（从外科和血液学/肿瘤学部门招募）和800例对照（按年龄和种族进行频率匹配）。将使用自填式问卷收集其他已知乳腺癌风险因素的数据，如人口统计学因素、癌症家族史、药物治疗、电离辐射暴露、吸烟和乙醇消费。第一项研究是评估DNA修复在人类乳腺癌风险中的作用。工作假设是乳腺癌风险与DNA修复缺陷/缺陷有关。丝裂原活化的外周T淋巴细胞将用于DNA修复功能测量。基因组DNA将用于确定DNA修复基因的遗传变体（即，XRCC 1、XRCC 3、XPD、APE和PARP）。第二项研究是评估药物代谢酶、GSTT 1/M1和膳食脂肪在人类乳腺癌风险中的相互作用。工作假设是GSTM 1/T1基因型无效的女性不能有效地解毒活性自由基，这可能导致脂质过氧化，氧化DNA损伤。基因组DNA将用于GSTT 1/M1基因分型。血浆样本将用于测量脂肪酸谱和脂质过氧化水平。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will use a cancer case-control study design to evaluate two hypotheses. The study subjects will include 800 incident breast cancer cases (recruited from the Departments of Surgery and Hematology/Oncology) and 800 controls (frequency-matched by age and race). A self-administered questionnaire will be used to collect data on other known breast cancer risk factors - such as demographic factors, family history of cancer, medication, ionizing radiation exposure, smoking, and ethanol consumption. The first study is to evaluate the role of DNA repair in human breast cancer risk. The working hypothesis is that breast cancer risk is associated with defective/deficient DNA repair. Mitogen-activated peripheral T-lymphocytes will be used for DNA repair functional measurements. Genomic DNA will be used for the determination of genetic variants of DNA repair genes (i.e., XRCC1, XRCC3, XPD, APE, and PARP). The second study is to evaluate the interaction between drug metabolism enzymes, GSTT1/M1 and dietary fat in human breast cancer risk. The working hypothesis is that women with null GSTM1/T1 genotypes cannot effectively detoxify reactive free radicals, which may lead to lipid peroxidation, oxidative DNA damage. Genomic DNA will be used for the GSTT1/M1 genotyping. Plasma samples will be used to measure fatty acid profile and lipid peroxidation levels.