Determinants of genetic penetrance in identical twins with breast cancer

技术摘要 在任何人群中，由于存在100多个遗传决定因素，大多数乳腺癌 病例很可能携带一种病毒，但社区发病主要由非遗传风险因素决定。 成年同卵双胞胎妇女在遗传和发育方面都是起源人群的代表。 非遗传因素。然而，当一个人患乳腺癌时，双胞胎中的另一个人的终生风险是 比预期的要高得多，因为这对一个普通的姐妹来说是危险的。即便如此，只有大约一个 四分之一这样的双胞胎会受到影响，而那些被诊断出来的人是在几年后。因此 受影响的对，无论是乳腺癌不一致还是一致，在表达水平上不同， 由于一致病例携带的遗传决定因素不太可能与那些 在不一致的情况下，这种受影响的对之间的差异，给定相同的遗传 决定因素，也反映了不同程度的焦虑。我们建议核实 不一致和一致对之间的遗传决定因素（使用Illumina OncoArray 500K），并记录外源性决定因素的存在和时间， 更高的反射率。这将是不和谐的对内，和谐的成员之间， 诊断时年龄不同的对，以及来自不一致和一致对的病例之间， 相同或相似的基因型。我们将使用成年双胞胎的记录能力， 他们之间的行为，环境暴露和给定的童年差异 强调青春期的发展速度。我们还将使用Illumina HM450K BeadArray，以评价报告的来自 病例归因于高风险基因型，以及成功治疗后是否持续。

Technical Abstract In any population, with the presence of more than 100 genetic determinants, most breast cancer cases are likely to carry one, yet community occurrence is dominated by non-genetic risk factors. Adult identical twin women are representative of the population of origin in both genetic and non-genetic factors. However, when one gets breast cancer, the lifetime risk to the co-twin is much higher than expected on the basis of risk to an ordinary sister. Even so, only about a quarter of such co-twins become affected, and those that are become diagnosed years later. Thus affected pairs, whether breast cancer discordant or concordant, differ in the level of penetrance, and since the genetic determinants carried by concordant cases are unlikely to differ from those in discordant cases, the difference between such affected pairs, given the same genetic determinants, also reflects a different level of penetrance. We propose to verify the identity of genetic determinants between discordant and concordant pairs (using the Illumina OncoArray 500K), and to document the existence and timing of exogenous determinants of higher penetrance. This will be within discordant pairs, between the members of concordant pairs differing in age at diagnosis, and between cases from discordant and concordant pairs with the same or similar genotype. We will use adult twins' documented ability to accurately recall childhood differences between themselves in behaviors, environmental exposures, and given currant emphasis on adolescence, the rate of development. We will also use the Illumina HM450K BeadArray to evaluate whether the reported global hypo-methylation of WBCs from cases is attributable to the high risk genotype, and whether it persists after successful treatment.