Department of Genetics and Biotechnology, University College of Science, Osmania University, Hyderabad, India.
Nizams Institute of Medical Sciences (NIMS), Hyderabad, Telangana, India.
Asian Pac J Cancer Prev. 2023 Mar 1;24(3):859-865. doi: 10.31557/APJCP.2023.24.3.859.
Breast cancer recurrence and metastasis are associated with alterations in the cellular stress responses that influence tumour signalling. Sirtuin3 (SIRT3), a mitochondrial deacetylase is the regulator of mitochondrial metabolism and oxidative stress affecting tumour cell responses. Genetic variants or dysregulation of SIRT3 was known to associate with poor prognosis of recurrence and relapse in few cancers.
The current case-control study was conducted in Hyderabad, India. A total of 200 primary female breast cancer cases were recruited, irrespective of age and clinical subtype. However, secondary or recurrent breast cancer cases were excluded from the study. A total of 202 age and gender-matched healthy controls without any familial inheritance of either breast or other cancer and having similar ethnicity as cases were recruited. The blood samples of both cases and controls were collected from Nizam's Institute of Medical Sciences (NIMS), Hyderabad. Our study is an attempt to evaluate the association of SIRT3 VNTR polymorphism in intron 5 with the development and progression of breast cancer by PCR-based genotyping. Result: The statistical analysis of the results with respect to epidemiological and clinical phenotypes revealed significant association of 0R allele and 0R/0R genotype with breast cancer risk (p<0.01). The odds ratios also were found to be significant i.e., 0R/0R [OR(CI): 2.67(1.54-4.65); p=0.000005] genotype. Also, the epidemiological and clinical variables have shown significant association with the risk of onset of the disease. Therefore, the influence of lack of repeats at intron 5 harbouring enhancer site on altered expression of SIRT3 might confer increased susceptibility to breast cancer.
The VNTR polymorphism in the intron 5 region of SIRT3 gene could serve as a molecular marker for detection of breast cancer onset. Further studies are warranted to study the prognostic and therapeutic significance of this SIRT3 polymorphism.
乳腺癌的复发和转移与影响肿瘤信号的细胞应激反应的改变有关。Sirtuin3（SIRT3）是一种线粒体去乙酰化酶，是调节线粒体代谢和氧化应激的关键因子，影响肿瘤细胞的反应。SIRT3 的遗传变异或失调与少数癌症的复发和预后不良有关。
本病例对照研究在印度海得拉巴进行。共招募了 200 名原发性女性乳腺癌患者，无论年龄和临床亚型如何。然而，继发性或复发性乳腺癌病例被排除在研究之外。共招募了 202 名年龄和性别匹配的健康对照者，他们没有乳腺癌或其他癌症的家族遗传史，并且与病例具有相似的种族。病例和对照者的血液样本均来自海得拉巴的尼扎姆医学科学研究所（NIMS）。我们的研究旨在通过基于 PCR 的基因分型评估 SIRT3 内含子 5 中的 VNTR 多态性与乳腺癌发生和发展的相关性。
对流行病学和临床表型的结果进行统计分析显示，0R 等位基因和 0R/0R 基因型与乳腺癌风险显著相关（p<0.01）。比值比也具有显著意义，即 0R/0R[OR（CI）：2.67（1.54-4.65）；p=0.000005]基因型。此外，流行病学和临床变量与疾病发病风险也有显著关联。因此，内含子 5 中增强子位点缺失重复序列可能会导致 SIRT3 表达改变，从而增加乳腺癌的易感性。
SIRT3 基因内含子 5 区的 VNTR 多态性可作为乳腺癌发病的分子标志物。进一步的研究需要研究这种 SIRT3 多态性的预后和治疗意义。
