2号染色体q35区域和16号染色体q12区域的常见变异会增加雌激素受体阳性乳腺癌的易感性。
Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.
作者信息
Stacey Simon N, Manolescu Andrei, Sulem Patrick, Rafnar Thorunn, Gudmundsson Julius, Gudjonsson Sigurjon A, Masson Gisli, Jakobsdottir Margret, Thorlacius Steinunn, Helgason Agnar, Aben Katja K, Strobbe Luc J, Albers-Akkers Marjo T, Swinkels Dorine W, Henderson Brian E, Kolonel Laurence N, Le Marchand Loic, Millastre Esther, Andres Raquel, Godino Javier, Garcia-Prats Maria Dolores, Polo Eduardo, Tres Alejandro, Mouy Magali, Saemundsdottir Jona, Backman Valgerdur M, Gudmundsson Larus, Kristjansson Kristleifur, Bergthorsson Jon T, Kostic Jelena, Frigge Michael L, Geller Frank, Gudbjartsson Daniel, Sigurdsson Helgi, Jonsdottir Thora, Hrafnkelsson Jon, Johannsson Jakob, Sveinsson Thorarinn, Myrdal Gardar, Grimsson Hlynur Niels, Jonsson Thorvaldur, von Holst Susanna, Werelius Barbro, Margolin Sara, Lindblom Annika, Mayordomo Jose I, Haiman Christopher A, Kiemeney Lambertus A, Johannsson Oskar Th, Gulcher Jeffrey R, Thorsteinsdottir Unnur, Kong Augustine, Stefansson Kari
机构信息
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
出版信息
Nat Genet. 2007 Jul;39(7):865-9. doi: 10.1038/ng2064. Epub 2007 May 27.
Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.
家族聚集性研究表明，乳腺癌风险具有很大的遗传成分。为了识别新的乳腺癌风险变异，我们使用Illumina Hap300平台对1600名冰岛乳腺癌患者和11563名对照进行了约30万个单核苷酸多态性（SNP）的基因分型。然后我们在五个重复样本集中对选定的SNP进行了检测。总体而言，我们研究了4554名患病个体和17577名对照。有两个SNP与乳腺癌始终相关：在2号染色体q35区域的rs13387042，约25%的欧洲血统个体为A等位基因纯合子，其风险估计比非携带者高1.44倍；在16号染色体q12区域的rs3803662，约7%的个体为T等位基因纯合子，风险高1.64倍。这两个等位基因的风险都仅限于雌激素受体阳性肿瘤。目前，在包含rs13387042的连锁不平衡区域尚未发现相关基因。rs3803662位于TNRC9基因5'端附近，TNRC9是一种高迁移率族染色质相关蛋白，其表达与乳腺癌骨转移有关。
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