Mcinerney Niall, Colleran Gabrielle, Rowan Andrew, Walther Axel, Barclay Ella, Spain Sarah, Jones Angela M, Tuohy Stephen, Curran Catherine, Miller Nicola, Kerin Michael, Tomlinson Ian, Sawyer Elinor
Department of Surgery, Clinical Science Institute, University College Hospital, Galway, Ireland.
Breast Cancer Res Treat. 2009 Sep;117(1):151-9. doi: 10.1007/s10549-008-0235-7. Epub 2008 Nov 13.
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.
大规模关联研究已鉴定出易患乳腺癌的低外显率易感等位基因。8号染色体q24.21上的一个位点已被证明含有易患乳腺癌、卵巢癌、结直肠癌和前列腺癌的变异。8q24处风险变异的聚集表明，可能存在易患不止一种上皮癌的常见易感等位基因。本研究的目的，一是确定先前鉴定出的乳腺癌易感等位基因是否与爱尔兰西部的散发性乳腺癌相关，二是确定是否存在易患所有三种常见上皮癌（乳腺癌、前列腺癌、结肠癌）的易感等位基因。我们对一组24个单核苷酸多态性（SNP）进行了基因分型，这些SNP最近被证明与前列腺癌、结直肠癌或乳腺癌易感性有关，研究对象为来自爱尔兰西部的988例散发性乳腺癌病例和1016名对照。然后，我们使用标准的荟萃分析技术，将我们的数据与公开可用的数据集相结合。已知的乳腺癌SNP rs13281615、rs2981582和rs3803662被证实与爱尔兰西部人群的乳腺癌风险相关（等位基因检验P值分别为1.8×10⁻²，比值比（OR）=1.17；等位基因检验P值=2.2×10⁻³，OR = 1.22；等位基因检验P值=5.1×10⁻²，OR = 1.15）。对于其余5个研究的乳腺癌SNP，在爱尔兰西部人群中没有证据表明它们与乳腺癌有关联（等位基因检验P值>6.5×10⁻²）。无论是位于8q24还是其他位置的前列腺癌或结直肠癌易感SNP，均与乳腺癌风险无关。荟萃分析证实，除已知易患结直肠癌和前列腺癌的rs6983269外，所有易感SNP均具有位点特异性。本研究证实，FGFR₂、8q24和TNCR9处的易感位点易导致爱尔兰西部的散发性乳腺癌。研究还表明，乳腺癌、前列腺癌和结直肠癌的低外显率易感SNP是不同的。虽然8q24含有易患所有三种癌症的变异，但该区域内的易感位点似乎对不同癌症类型具有特异性，结直肠癌和前列腺癌中的rs6983269除外。
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