Hashemi Mohammad, Amininia Shadi, Ebrahimi Mahboubeh, Hashemi Seyed Mehdi, Taheri Mohsen, Ghavami Saeid
Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
BMC Res Notes. 2014 Dec 10;7:895. doi: 10.1186/1756-0500-7-895.
Breast cancer (BC) is considered to be one of the most important causes of death worldwide, and it affects the Iranian female population a decade earlier than female in other parts of the world. Human telomerase reverse transcriptase (hTERT) is a main subunit of the telomerase complex. MNS16A is located downstream of the hTERT gene and is recognized as the regulator of hTERT promoter activity. The aim of the present study was to access the possible impact of hTERT variants on BC risk in an Iranian population in southeast Iran.
A total of 491 subjects including 266 BC patients and 225 healthy women participated in the study. Polymerase chain reaction (PCR) was used to genotype the MNS16A variable number of tandem repeats and 177 bp ins/del polymorphisms in the hTERT gene. PCR-RFLP and ARMS-PCR were used to genotype hTERT rs2736098 and 2735940, respectively. The association between genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CI) from logistic regression analyses. A p-value of <0.05 was considered statistically significant.
The MNS16A genotype frequency distribution in BC patients was: LL, 43.2%; LS, 51.1%; and SS, 5.7%, and in controls: LL, 29.5%; LS, 68.3%; and SS, 2.2%. The LS genotype decreased the risk of BC compared with LL (OR=0.51, 95% CI=0.35-0.75, p<0.001). The hTERT 177 bp ins/del polymorphism was not polymorphic in our population. All subjects had the ins/ins genotype. Our findings indicate that the MNS16A genotype and hTERT rs2736098 variant were associated with BC risk in the study. We also showed that the rs2736098 A/G polymorphism increased the risk of BC (OR=1.80, 95% CI=1.12-2.88, p=0.017, AG vs AA; OR=1.80, 95% CI=1.06-3.06, p=0.033, GG vs AA; OR=1.87, 95% CI=1.19-2.94, p=0.006, AG+GG vs AA). No significant association was found between the rs2735940 C/T variant and BC.
Our findings indicate that the MNS16A genotype and the hTERT rs2736098 variant influence the risk of BC in an Iranian population in southeast Iran.
乳腺癌（BC）被认为是全球最重要的死亡原因之一，且伊朗女性患乳腺癌的年龄比世界其他地区的女性早十年。人端粒酶逆转录酶（hTERT）是端粒酶复合物的主要亚基。MNS16A位于hTERT基因下游，被认为是hTERT启动子活性的调节因子。本研究的目的是探讨hTERT基因变异对伊朗东南部人群患BC风险的可能影响。
共有491名受试者参与了本研究，其中包括266例BC患者和225名健康女性。采用聚合酶链反应（PCR）对hTERT基因中MNS16A可变串联重复序列和177 bp插入/缺失多态性进行基因分型。分别采用PCR-RFLP和ARMS-PCR对hTERT rs2736098和2735940进行基因分型。通过逻辑回归分析计算优势比（OR）和95%置信区间（95%CI），评估基因型与BC之间的关联。p值<0.05被认为具有统计学意义。
BC患者中MNS16A基因型频率分布为：LL型，43.2%；LS型，51.1%；SS型，5.7%；对照组中：LL型，29.5%；LS型，68.3%；SS型，2.2%。与LL基因型相比，LS基因型降低了BC风险（OR=0.51，95%CI=0.35-0.75，p<0.001）。hTERT 177 bp插入/缺失多态性在我们的研究人群中无多态性。所有受试者均为插入/插入基因型。我们的研究结果表明，在本研究中MNS16A基因型和hTERT rs2736098变异与BC风险相关。我们还发现rs2736098 A/G多态性增加了BC风险（OR=1.80，95%CI=1.12-2.88，p=0.017，AG与AA相比；OR=1.80，95%CI=1.06-3.06，p=0.033，GG与AA相比；OR=1.87，95%CI=1.19-2.94，p=0.006，AG+GG与AA相比）。未发现rs2735940 C/T变异与BC之间存在显著关联。
我们的研究结果表明，MNS16A基因型和hTERT rs2736098变异影响伊朗东南部人群患BC的风险。
