Nesa Ayatun, Mostafijur Rahman Md, Tahminur Rahman Md, Kabir Yearul
Department of Laboratory Medicine, BIRDEM General Hospital, Dhaka, Bangladesh.
Southern Illinois University, Carbondale IL-62901, USA.
Gene. 2023 Jun 5;868:147368. doi: 10.1016/j.gene.2023.147368. Epub 2023 Mar 23.
One of the leading causes of cancer-related mortality in males is prostate cancer. The latest molecular studies revealed the interconnection of genetic polymorphism of N acetyltransferase (NAT) and Glutathione-S-transferase (GST) gene in the genesis of prostate cancer. The study's aim was to find out the association of NAT2, GSTT1, and GSTM1 gene polymorphisms with the risk of prostate cancer in the Bangladeshi population. This case-control study included 207 histopathologically diagnosed cases of prostate cancer and 200 age-matched healthy controls. After taking informed written consent, 5.0 mL of venous blood was collected to extract genomic DNA for genetic analysis of NAT2, GSTT1& GSTM1 by PCR-RFLP by multiplex PCR methods. In this study, the mean ± SD age of cases and control was 67.3 ± 8.3, and 62.2 ± 6.8 years, respectively. A higher frequency of mutant NAT25A, NAT26A, and NAT2*7A in prostate cancer cases was observed in this study, in comparison to controls. Prostate cancer risk was found considerably increased in patients with NAT2 slow genotypes, GSTT1 and GSTM1 null genotypes, compared to control. Furthermore, Prostate cancer risk was found very significantly associated with the presence of combined genotypes that included NAT2 (slow), GSTT1 (null), and GSTM1 (null), and the risk rose 9.64-fold when compared to the wild genotype for NAT2, GSTT1, and GSTM1. Again, it was observed that individuals with positive smoking history/family history of cancer along with NAT2 slow genotype had significantly increased risk for prostate cancer. Moreover, the likelihood of developing a moderate to a high-grade tumor (Gleason score 7), as well as locally progressed or metastatic prostate cancer was considerably greater in persons with NAT2 slow genotypes, GSTT1, and GSTM1 null genotypes. This study established the association of genetic polymorphisms of NAT2, GSTT1, and GSTM1 genes with prostate cancer risk in the Bangladeshi population.
男性癌症相关死亡的主要原因之一是前列腺癌。最新的分子研究揭示了N - 乙酰转移酶（NAT）和谷胱甘肽 - S - 转移酶（GST）基因的基因多态性在前列腺癌发生过程中的相互联系。该研究的目的是找出NAT2、GSTT1和GSTM1基因多态性与孟加拉人群前列腺癌风险之间的关联。这项病例对照研究纳入了207例经组织病理学诊断的前列腺癌病例和200例年龄匹配的健康对照。在获得知情书面同意后，采集5.0 mL静脉血以提取基因组DNA，通过多重PCR方法采用PCR - RFLP对NAT2、GSTT1和GSTM1进行基因分析。在本研究中，病例组和对照组的平均年龄±标准差分别为67.3±8.3岁和62.2±6.8岁。与对照组相比，本研究观察到前列腺癌病例中突变型NAT25A、NAT26A和NAT2*7A的频率更高。与对照组相比，发现NAT2慢基因型、GSTT1和GSTM1缺失基因型的患者前列腺癌风险显著增加。此外，发现前列腺癌风险与包括NAT2（慢）、GSTT1（缺失）和GSTM1（缺失）的联合基因型显著相关，与NAT2、GSTT1和GSTM1的野生基因型相比，风险增加了9.64倍。再次观察到，有吸烟史/癌症家族史且NAT2慢基因型的个体患前列腺癌的风险显著增加。此外，NAT2慢基因型、GSTT1和GSTM1缺失基因型的人发生中度至高度肿瘤（Gleason评分7）以及局部进展或转移性前列腺癌的可能性要大得多。这项研究确立了NAT2、GSTT1和GSTM1基因多态性与孟加拉人群前列腺癌风险之间的关联。
