Identification of Single Nucleotide Polymorphisms in Can

了解个体遗传背景在癌症易感性、疾病进展和治疗反应中的作用是癌症研究的重要组成部分。单核苷酸多态性（SNPs）是了解复杂疾病的一个丰富而有用的遗传标记来源。我们已经确定了雌激素受体基因（ESR1）的变异，并在一组乳腺癌患者中对这些变异进行了基因分型。结果表明，由该基因的几个多态性产生的单倍型与乳腺癌风险降低有关。此外，我们正在描述ESR2和黄体酮受体基因的变异。虽然没有发现这些基因的变异与乳腺癌有关，但它们可能与其他激素反应性癌症有关。tripartite motif-containing 5 （TRIM5）基因是一种新发现的参与保护细胞免受病毒感染的蛋白。我们已经对大量正常个体和HIV-1感染风险患者的TRIM5基因进行了测序。我们在基因中发现了大量的非同义变体，这表明这些变体已经被选择并赋予了对疾病的一些保护。此外，该基因仅在灵长类动物中保守，在小鼠、大鼠或狗的基因组中没有发现。证据还表明，在其他灵长类物种中，这种基因存在相当大的差异。

Understanding the role of individual genetic background in his/her susceptibility to cancer, disease progression, and response to therapy is an important component of cancer research. Single nucleotide polymorphisms (SNPs) represent an abundant and useful source of genetic markers to understand complex diseases. We have characterized variants in the estrogen receptor gene (ESR1) and genotyped these variants in a cohort of breast cancer patients. The results show that a haplotype generated by several polymorphisms in this gene is associated with a reduced risk of breast cancer. In addition, we are characterizing variants in the ESR2 and progesterone receptor genes. While variants in these genes were not found to be associated with breast cancer, they may be relevant to other hormone responsive cancers. The tripartite motif-containing 5 (TRIM5) gene represents a newly described protein involved in the protection of cells from viral infection. We have sequenced the TRIM5 gene in a large collection of normal individuals as well as patients at risk for HIV-1 infection. We find a large number of non-synonymous variants in the gene, suggesting that these variants have been selected for and confer some protection to disease. In addition, the gene is conserved only in primates and is not found in the genome of the mouse, rat or dog. Evidence also shows that there is considerable variation in the gene in other primate species.