Singh Vibha, Jaiswal Praveen Kumar, Mittal Rama Devi
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India.
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India.
Urol Oncol. 2014 Nov;32(8):1209-14. doi: 10.1016/j.urolonc.2014.05.013. Epub 2014 Sep 11.
Genome-wide association studies have confirmed association of TP63C/T rs710521, TERTC/T rs2736098, and SLC14A1C/T rs17674580 gene variants with susceptibility to bladder cancer (BC) in European and White population. However, the risk conferred for BC for above gene variants in North Indians is unknown. We therefore, studied the association of TP63C/T, TERTC/T, and SLC14A1C/T single nucleotide polymorphisms (SNPs) with a risk of BC susceptibility in North Indian cohort.
In histologically confirmed 225 BC cases and 240 healthy controls, 3 SNPs were genotyped by real-time polymerase chain reaction. To evaluate the SNP effects on BC susceptibility, odds ratio (OR) and CI 95% were calculated.
In case of TP63C/T, the variant genotype (TT) showed significant reduced risk for BC (P = 0.045, OR = 0.53). Combining heterozygous and variant genotypes also demonstrated reduced risk for BC (P< 0.001, OR = 0.54). In case of TERTC/T, heterozygous genotype (CT) as well as variant genotype (TT) showed significant risk for BC susceptibility (P = 0.031, OR = 1.77 and P = 0.004, OR = 2.78, respectively) along with T allelic level (P<0.001, OR = 4.19). Furthermore, in case of SLC14A1C/T gene polymorphism, the variant genotype (TT) showed significant high risk for BC susceptibility (P = 0.006; OR = 3.01) along with variant T allelic level (P = 0.003, OR = 1.52). Interestingly, smoking was also found to modulate risks for BC in case of TERT and SLC14A1 variant genotype (TT). Further clinical confounding factor, namely, tumor grade/stage level of cases, supports the genotypic data with TERT and SLC14A1 showing a risk for BC susceptibility.
Our results suggested that polymorphism in TERTC/T and SLC14A1C/T confirmed high risk for BC in North Indian population. However, TP63C/T showed reduced risk of BC susceptibility. More replicate studies with large sample size and diverse ethnicity are required to validate these observations.
全基因组关联研究已证实，在欧洲和白人人群中，TP63C/T rs710521、TERTC/T rs2736098和SLC14A1C/T rs17674580基因变异与膀胱癌（BC）易感性相关。然而，上述基因变异在北印度人群中对BC的风险尚不清楚。因此，我们研究了TP63C/T、TERTC/T和SLC14A1C/T单核苷酸多态性（SNP）与北印度队列中BC易感性风险的关联。
在225例经组织学确诊的BC病例和240例健康对照中，通过实时聚合酶链反应对3个SNP进行基因分型。为评估SNP对BC易感性的影响，计算比值比（OR）和95%置信区间（CI）。
就TP63C/T而言，变异基因型（TT）显示BC风险显著降低（P = 0.045，OR = 0.53）。杂合基因型和变异基因型合并显示BC风险也降低（P < 0.001，OR = 0.54）。就TERTC/T而言，杂合基因型（CT）以及变异基因型（TT）显示BC易感性风险显著增加（分别为P = 0.031，OR = 1.77和P = 0.004，OR = 2.78），T等位基因水平也是如此（P < 0.001，OR = 4.19）。此外，就SLC14A1C/T基因多态性而言，变异基因型（TT）显示BC易感性风险显著增加（P = 0.006；OR = 3.01），变异T等位基因水平也是如此（P = 0.003，OR = 1.52）。有趣的是，在TERT和SLC14A1变异基因型（TT）的情况下，吸烟也被发现可调节BC风险。进一步的临床混杂因素，即病例的肿瘤分级/分期水平，支持了TERT和SLC14A1的基因型数据显示BC易感性风险增加。
我们的结果表明，TERTC/T和SLC14A1C/T多态性证实了北印度人群中BC的高风险。然而，TP63C/T显示BC易感性风险降低。需要更多大样本量和不同种族的重复研究来验证这些观察结果。
