Pooley Karen A, Healey Catherine S, Smith Paula L, Pharoah Paul D P, Thompson Deborah, Tee Louise, West Judith, Jordan Clare, Easton Douglas F, Ponder Bruce A J, Dunning Alison M
Department of Oncology, Cancer Research UK, University of Cambridge, Strangeways Research Laboratory.
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):675-82. doi: 10.1158/1055-9965.EPI-05-0679.
Association studies on susceptibility to breast cancer using single nucleotide polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously published, but the results have been inconclusive. We used a comprehensive SNP-tagging approach to search for low-penetrance susceptibility alleles in a study of up to 4,647 cases and 4,564 controls, in a two-stage study design. We identified seven tagging SNPs using genotype data from the National Institute of Environmental Health Sciences (NIEHS) Environmental Genome Project and typed these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284 controls (set 1). Three SNPs showed no evidence for association and were not studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068, rs500760, rs566351, and rs1042838) exhibited significant associations at P < 0.1 using either a heterogeneity or trend test and progressed to be genotyped in set 2. After both stages, only one SNP was significantly associated with an increased risk of breast cancer - the PGR-12 (rs1042638) V660L valine to leucine polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03-1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98-1.73), P(het) = 0.008, P(trend) = 0.002]. Similar estimates were obtained in a combined analysis of our data with those from three other published studies. We conclude that the 660L allele may be associated with a moderately increased risk of breast cancer, but that other common SNPs in the PGR gene are unlikely to be associated with a substantial risk of breast cancer.
此前已有关于利用孕激素受体（PGR）基因中的单核苷酸多态性（SNP）进行乳腺癌易感性关联研究的报道，但结果尚无定论。在一项两阶段研究设计中，我们采用全面的SNP标签法，在多达4647例病例和4564例对照中寻找低外显率易感性等位基因。我们利用美国国立环境卫生科学研究所（NIEHS）环境基因组计划的基因型数据鉴定出7个标签SNP，并在2345例乳腺癌病例和2284例对照（第1组）中对这些以及另外3个SNP进行基因分型。3个SNP未显示出关联证据，未作进一步研究，而7个SNP（rs11571171、rs7116336、rs660149、rs10895068、rs500760、rs566351和rs1042838）在使用异质性或趋势检验时，在P < 0.1水平显示出显著关联，并进入第2组进行基因分型。经过两个阶段后，只有一个SNP与乳腺癌风险增加显著相关——PGR - 12（rs1042638）的V660L缬氨酸到亮氨酸多态性[VL杂合子（比值比，1.13；95%置信区间，1.03 - 1.24）和LL纯合子（比值比，1.30；95%置信区间，0.98 - 1.73），P（het） = 0.008，P（趋势） = 0.002]。将我们的数据与其他三项已发表研究的数据进行联合分析时，得到了类似的估计值。我们得出结论，660L等位基因可能与乳腺癌风险适度增加相关，但PGR基因中的其他常见SNP不太可能与乳腺癌的实质性风险相关。
