ECOGENETICS OF PANCREATIC CANCER--FAMILY REGISTRY

描述：胰腺癌，主要为外分泌腺癌。 胰腺是导致癌症死亡的第五大原因，据估计 1996年新增26300例，死亡27800例。生存是可怕的，没有 目前有早期筛查方法可用。疑似环境问题 决定因素包括烟草使用、各种职业暴露、高 饮食中的脂肪摄入，也许还有电离辐射。疑似遗传 决定因素包括癌基因k-ras的体细胞突变和各种 染色体区域(1p，3p，6q，8p和17p，细胞遗传学；5q，8p， 1p33和11q13，表现为遗传异质性丧失)，以及罕见的孟德尔 病症(例如遗传性胰腺炎、遗传性发育不良痣 综合征、遗传性非息肉病、结直肠癌、遗传性心脏病和 BRCA2导致的卵巢癌和Li-Fraumeni癌症家族综合征)。 使用拟议策略的家庭研究之前已经产生了洞察力 各种癌症的起源，包括结直肠癌、乳腺癌和 肉瘤；同样的方法可能对胰腺癌有用。 具体目标1是更新肺腺癌的家族聚集性 胰腺。一项关于胰腺癌家庭的全国性登记已经完成。 已启动，本申请中的计划用于更新现有的71 家庭和13个临时家庭，并在总数为150个的基础上增加新的家庭 在4年内。将完成环境和医学调查问卷 用于胰腺癌患者和对照组。具体目标2是获得 来自登记家庭的生物标本和保存标本 存储库。所有癌症的历史都将用医学记录下来 记录；幻灯片、组织块、DNA和血清将组装在可用 患者及其一级亲属。具体目标3是进行 对登记材料的初步分析和化验。协作将 在样本上进行试点工作(即，针对 TP53、BRCA2、激活的k-ras等癌基因、二核苷酸重复序列 不稳定性、细胞遗传学和组织病理学回顾)。来自的系列血清 一级亲属，谁可以被认为风险增加，将是 检测一系列肿瘤标志物，包括CEA、CA125、CA19-9和 CA242，用于前瞻性检测有症状的癌症。

DESCRIPTION: Pancreatic cancer, mostly adenocarcinoma of the exocrine pancreas, is the 5th leading cause of cancer deaths, totalling an estimated 26,300 new cases and 27,800 deaths in 1996. Survival is abysmal and no early screening methods are currently available. Suspected environmental determinants include tobacco use, various occupational exposures, high dietary fat intake, and perhaps ionizing radiation. Suspected genetic determinants include somatic mutations in the oncogene k-ras and various chromosome regions (1p, 3p, 6q, 8p, and 17p, seen cytogenetically; 5q, 8p, 1p33, and 11q13, seen by loss of genetic heterogeneity), and rare Mendelian conditions (e.g., hereditary pancreatitis, hereditary dysplastic nevus syndrome, hereditary nonpolyposis colorectal cancer, hereditary heart and ovarian cancer due to BRCA2, and the Li-Fraumeni cancer family syndrome). Family studies, using the proposed strategy have previously yielded insights into the origins of various cancers, including colorectal, breast, and sarcoma; the same approach is likely to be useful in pancreatic cancer. Specific Aim 1 is to update familial aggregations of adenocarcinoma of the pancreas. A national registry of families with pancreatic cancer has been initiated and the plans in this application are for updating the 71 current families and 13 provisional families, and adding new ones to a total 150 within 4 years. Environmental and medical questionnaires will be completed for pancreatic cancer patients and a control. Specific Aim 2 is to acquire biologic specimens from registered families and maintain a specimen repository. The history of all cancers will be documented with medical records; slides, tissue blocks, DNA and sera will be assembled on available patients and their first degree relatives. Specific Aim 3 is to conduct preliminary analyses and assays on registry material. Collaborations will be struck to conduct pilot work on the specimens (viz., for mutations in TP53, BRCA2, activated k-ras and other oncogenes, dinucleotide repeats instability, cytogenetics, and review of histopathology). Serial sera from first degree relatives, who can be considered at increased risk, will be assayed for a battery of tumor markers, including CEA, CA125, CA19-9, and CA242, to prospectively detect pre-symptomatic cancer.