miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
miR-485-5p Binding Site SNP rs8752 in HPGD Gene Is Associated with Breast Cancer Risk
复制标题
HPGD 基因中的 miR-485-5p 结合位点 SNP rs8752 与乳腺癌风险相关
DOI：
10.1371/journal.pone.0102093
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发表时间：
2014-07-08
期刊：
影响因子：
3.7
通讯作者：
Chen, Kexin
中科院分区：
文献类型：
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作者：
He, Na;Zheng, Hong;Chen, Kexin
背景 存在于 microRNA 靶位点的单核苷酸多态性 (SNP) 可能在乳腺癌的发生和进展中发挥重要作用。为了揭示 microRNA 靶位点 SNP 与乳腺癌风险之间的关联，我们在中国进行了一项大型病例对照研究。方法 我们进行了一项两阶段病例对照研究，包括 2744 例乳腺癌病例和 3125 例对照。在第一阶段，我们使用 Illumina BeadXpress 平台上的定制 Illumina GoldenGate VeraCode 检测对从“Patrocles”数据库中识别出的 microRNA 结合位点内的 192 个 SNP 进行了基因分型。在第二阶段，使用 TaqMan 平台在独立的复制集中对可能与乳腺癌风险相关的 SNP 进行基因分型。结果 在第一阶段，有 15 个 SNP 被确定与乳腺癌风险显着相关（P<0.05）。在第二阶段，一个SNP rs8752被复制，P<0.05。该 SNP 位于 15-羟基前列腺素脱氢酶 (HPGD) 基因 4q34-35 的 3' 非翻译区 (UTR)，这是 miR-485-5p 结合位点。与GG基因型相比，GA+AA基因型组合患乳腺癌的风险显着升高（OR = 1.18；95% CI：1.06-1.31，P = 0.002）。具体来说，该 SNP 与雌激素受体 (ER) 阳性乳腺癌相关 (P = 0.0007)，但与 ER 阴性乳腺癌无关 (P = 0.23)，尽管异质性 p 不显着。结论 通过对 microRNA 结合位点 SNP 的系统病例对照研究，我们在中国女性 HPGD 中发现了一个新的乳腺癌风险变异 rs8752。需要进一步研究来调查这种关联的基本机制。
Background Single nucleotide polymorphisms (SNPs) that reside in microRNA target sites may play an important role in breast cancer development and progression. To reveal the association between microRNA target site SNPs and breast cancer risk, we performed a large case-control study in China. Methods We performed a two-stage case-control study including 2744 breast cancer cases and 3125 controls. In Stage I, we genotyped 192 SNPs within microRNA binding sites identified from the “Patrocles” database using custom Illumina GoldenGate VeraCode assays on the Illumina BeadXpress platform. In Stage II, genotyping was performed on SNPs potentially associated with breast cancer risk using the TaqMan platform in an independent replication set. Results In stage I, 15 SNPs were identified to be significantly associated with breast cancer risk (P<0.05). In stage II, one SNP rs8752 was replicated at P<0.05. This SNP is located in the 3’ untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene at 4q34-35, a miR-485-5p binding site. Compared with the GG genotype, the combined GA+AA genotypes has a significantly higher risk of breast cancer (OR = 1.18; 95% CI: 1.06-1.31, P = 0.002). Specifically, this SNP was associated with estrogen receptor (ER) positive breast cancer (P = 0.0007), but not with ER negative breast cancer (P = 0.23), though p for heterogeneity not significant. Conclusion Through a systematic case-control study of microRNA binding site SNPs, we identified a new breast cancer risk variant rs8752 in HPGD in Chinese women. Further studies are warranted to investigate the underling mechanism for this association.