Rashid Muhammad Usman, Muzaffar Merium, Khan Faiz Ali, Kabisch Maria, Muhammad Noor, Faiz Sabeen, Loya Asif, Hamann Ute
Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan; Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan; Department of Physiology, University of Health Sciences, Lahore, Pakistan.
PLoS One. 2015 Oct 30;10(10):e0141562. doi: 10.1371/journal.pone.0141562. eCollection 2015.
Vitamin D is postulated to decrease the risk of breast cancer by inhibiting cell proliferation via the vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNPs) in the VDR gene, rs1544410 (BsmI) and rs2228570 (FokI), are inconsistently associated with breast cancer risk in Caucasian populations, while data for Asians are scarce. Here, we investigated the possible contribution of these SNPs to breast cancer risk in Pakistani breast cancer patients and in controls participating in a hospital-based breast cancer case-control study (PAK-BCCC).
Genotyping of the BsmI and FokI SNPs was performed by PCR-based restriction fragment length polymorphism (RFLP) analysis of 463 genetically enriched female breast cancer cases with known BRCA1/2 status and in 1,012 controls from Pakistan. The association between SNP genotypes and breast cancer risk was investigated by logistic regression adjusted for potential breast cancer risk factors and stratified by BRCA1/2 status and family history. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported.
The b allele of the BsmI was associated with an increased breast cancer risk (per b allele OR 1.28, 95% CI 1.09-1.49, P = 0.003). Subgroup analysis revealed that this effect was restricted to BRCA1/2 non-carriers (per b allele OR 1.33, 95% CI 1.11-1.59, P = 0.002) and was stronger in those who reported a positive family history of breast and/or ovarian cancer (per b allele OR 1.64, 95% CI 1.20-2.22, P = 0.002). No association with breast cancer risk was detected for the FokI SNP.
The BsmI polymorphism in the VDR gene may be associated with an increased breast cancer risk in Pakistani women negative for BRCA1/2 germline mutations.
维生素D被认为可通过维生素D受体（VDR）抑制细胞增殖，从而降低患乳腺癌的风险。VDR基因中的两个常见单核苷酸多态性（SNP），即rs1544410（BsmI）和rs2228570（FokI），在白种人群中与乳腺癌风险的关联并不一致，而亚洲人群的数据则很少。在此，我们调查了这些SNP对参与一项基于医院的乳腺癌病例对照研究（PAK - BCCC）的巴基斯坦乳腺癌患者和对照者患乳腺癌风险的可能影响。
通过基于聚合酶链反应（PCR）的限制性片段长度多态性（RFLP）分析，对463例已知BRCA1/2状态的遗传富集女性乳腺癌病例以及1012名来自巴基斯坦的对照者进行BsmI和FokI SNP基因分型。通过对潜在乳腺癌风险因素进行校正的逻辑回归分析，并按BRCA1/2状态和家族史分层，研究SNP基因型与乳腺癌风险之间的关联。报告比值比（OR）和95%置信区间（CI）。
BsmI的b等位基因与乳腺癌风险增加相关（每个b等位基因的OR为1.28，95%CI为1.09 - 1.49，P = 0.003）。亚组分析显示，这种效应仅限于BRCA1/2非携带者（每个b等位基因的OR为1.33，95%CI为1.11 - 1.59，P = 0.002），并且在报告有乳腺癌和/或卵巢癌家族史阳性的人群中更强（每个b等位基因的OR为1.64，95%CI为1.20 - 2.22，P = 0.002）。未检测到FokI SNP与乳腺癌风险的关联。
VDR基因中的BsmI多态性可能与BRCA1/2种系突变阴性的巴基斯坦女性患乳腺癌风险增加有关。
