Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
PLoS One. 2013 Aug 5;8(8):e71073. doi: 10.1371/journal.pone.0071073. Print 2013.
Cell surface biomarker CD44 plays an important role in breast cancer cell growth, differentiation, invasion, angiogenesis and tumour metastasis. Therefore, we aimed to investigate the role of CD44 gene polymorphisms in breast cancer risk and prognosis in North Indian population.
MATERIALS & METHODS: A total of 258 breast cancer patients and 241 healthy controls were included in the case-control study for risk prediction. According to RECIST, 114 patients who received neo-adjuvant chemotherapy were recruited for the evaluation of breast cancer prognosis. We examined the association of tagging SNP (rs353639) of Hapmap Gujrati Indians in Houston (GIH population) in CD44 gene along with a significant reported SNP (rs13347) in Chinese population by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. In-silico analysis for prediction of functional effects was done using F-SNP and FAST-SNP.
No significant association of both the genetic variants of the CD44 gene polymorphisms was found with breast cancer risk. On performing univariate analysis with clinicopathological characteristics and treatment response, we found significant association of genotype (CT+TT) of rs13347 polymorphism with earlier age of onset (P = 0.029, OR = 0.037). However, significance was lost in multivariate analysis. For rs353639 polymorphism, significant association was seen with clinical tumour size, both at the genotypic (AC+CC) (P = 0.039, OR = 3.02) as well as the allelic (C) (P = 0.042, OR = 2.87) levels. On performing multivariate analysis, increased significance of variant genotype (P = 0.017, OR = 4.29) and allele (P = 0.025, OR = 3.34) of rs353639 was found with clinical tumour size. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs353639 polymorphism.
These findings suggest that CD44 rs353639 genetic variants may have significant effect in breast cancer prognosis. However, both the polymorphisms- rs13347 and rs353639 had no effect on breast cancer susceptibility.
细胞表面标志物 CD44 在乳腺癌细胞的生长、分化、侵袭、血管生成和肿瘤转移中起着重要作用。因此，我们旨在研究 CD44 基因多态性在北印度人群中乳腺癌风险和预后中的作用。
在风险预测的病例对照研究中，共纳入 258 例乳腺癌患者和 241 例健康对照者。根据 RECIST 标准，招募了 114 例接受新辅助化疗的患者，评估乳腺癌的预后。我们通过 Taqman 等位基因鉴别分析，检测了 Hapmap 休斯敦古吉拉特人（GIH 人群）中 CD44 基因的标记 SNP（rs353639）与中国人群中报道的显著 SNP（rs13347）的关联。使用 SPSS 软件，版本 17 进行统计分析。使用 F-SNP 和 FAST-SNP 进行功能效应预测的计算机分析。
未发现 CD44 基因多态性的两种遗传变异与乳腺癌风险显著相关。对临床病理特征和治疗反应进行单变量分析，发现 rs13347 多态性的基因型（CT+TT）与发病年龄较早显著相关（P = 0.029，OR = 0.037）。然而，在多变量分析中，这种关联消失了。对于 rs353639 多态性，在基因型（AC+CC）（P = 0.039，OR = 3.02）和等位基因（C）（P = 0.042，OR = 2.87）水平上，均观察到与临床肿瘤大小显著相关。进行多变量分析后，发现 rs353639 变异基因型（P = 0.017，OR = 4.29）和等位基因（P = 0.025，OR = 3.34）与临床肿瘤大小的相关性显著增加。使用 F-SNP 进行的计算机分析表明，rs353639 多态性改变了转录调控。
这些发现表明，CD44 rs353639 遗传变异可能对乳腺癌的预后有显著影响。然而，rs13347 和 rs353639 这两种多态性对乳腺癌的易感性没有影响。
