Low penetrance breast cancer predisposition SNPs are site specific
Low penetrance breast cancer predisposition SNPs are site specific
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DOI：
10.1007/s10549-008-0235-7
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Sawyer, Elinor
中科院分区：
文献类型：
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作者：
Mcinerney, Niall;Colleran, Gabrielle;Sawyer, Elinor
大规模的关联研究已经确定了易患乳腺癌的低频率易感等位基因。染色体8q24.21上的一个基因座已被证明含有易患乳腺癌、卵巢癌、结肠直肠癌和前列腺癌的变异。在8 q24聚集的风险变异的发现表明，可能存在共同的易感等位基因，易患多种上皮癌。本研究的目的是首先确定是否以前确定的乳腺癌易感等位基因与散发性乳腺癌在西部的爱尔兰，其次，以确定是否有易感等位基因，易患所有三种常见的上皮癌（乳腺癌，前列腺癌，结肠癌）。我们对来自爱尔兰西部的988例散发性乳腺癌病例和1,016例对照组中的24个SNP进行了基因分型，这些SNP最近被证明易患前列腺癌、结直肠癌或乳腺癌。然后，我们使用标准的荟萃分析技术将我们的数据与公开的数据集结合起来。已知的乳腺癌SNPs rs 13281615、rs 2981582和rs3803662被证实与乳腺癌风险相关（P（等位基因测试）= 1.8 x 10（-2），OR = 1.17; P（等位基因测试）= 2.2 x 10（-3），OR = 1.22; P（等位基因测试）= 5.1 x 10（-2），OR = 1.15）。对于剩下的5个乳腺癌SNPs的研究，没有证据表明与西爱尔兰人群中的乳腺癌相关（P（等位基因检验）> 6.5 x 10（-2））。在前列腺或结直肠的易感性SNPs之间也没有关联，无论是在8 q24或其他地方，与乳腺癌的风险。荟萃分析证实，所有易感性SNP都具有位点特异性，除了已知易患结直肠癌和前列腺癌的rs6983269。这项研究证实，在爱尔兰西部，FGFR 2、8 q24和TNCR 9的易感基因座易患散发性乳腺癌。这也表明乳腺癌、前列腺癌和结直肠癌的低转移易感性SNP是不同的。尽管8 q24含有易患所有三种癌症的变体，但该区域内的易感基因座似乎对不同癌症类型具有特异性，除了结肠癌和前列腺癌中的rs6983269。
Large scale association studies have identified low penetrance susceptibility alleles that predispose to breast cancer. A locus on chromosome 8q24.21 has been shown to harbour variants that predispose to breast, ovarian, colorectal and prostate cancer. The finding of risk variants clustering at 8q24 suggests that there may be common susceptibility alleles that predispose to more than one epithelial cancer. The aim of this study was firstly to determine whether previously identified breast cancer susceptibility alleles are associated with sporadic breast cancer in the West of Ireland and secondly to ascertain whether there are susceptibility alleles that predispose to all three common epithelial cancers (breast, prostate, colon). We genotyped a panel of 24 SNPs that have recently been shown to predispose to prostate, colorectal or breast cancer in 988 sporadic breast cancer cases and 1,016 controls from the West of Ireland. We then combined our data with publicly available datasets using standard techniques of meta-analysis. The known breast cancer SNPs rs13281615, rs2981582 and rs3803662 were confirmed as associated with breast cancer risk (P (allelic test) = 1.8 x 10(-2), OR = 1.17; P (allelic test) = 2.2 x 10(-3), OR = 1.22; P (allelic test) = 5.1 x 10(-2), OR = 1.15, respectively) in the West of Ireland cohort. For the remaining five breast cancer SNPs that were studied there was no evidence of an association with breast cancer in the West Ireland population (P (allelic test) > 6.5 x 10(-2)). There was also no association between any of the prostate or colorectal susceptibility SNPs, whether at 8q24 or elsewhere, with breast cancer risk. Meta-analysis confirmed that all susceptibility SNPs were site specific, with the exception of rs6983269 which is known to predispose to both colorectal and prostate cancer. This study confirms that susceptibility loci at FGFR2, 8q24 and TNCR9 predispose to sporadic breast cancer in the West of Ireland. It also suggests that low penetrance susceptibility SNPs for breast, prostate and colorectal cancer are distinct. Although 8q24 harbours variants that predispose to all three cancers, the susceptibility loci within the region appear to be specific for the different cancer types with the exception of rs6983269 in colon and prostate cancer.