Rivu Sanzana Fareen, Apu Mohd Nazmul Hasan, Shabnaz Samia, Nahid Noor Ahmed, Islam Md Reazul, Al-Mamun Mir Md Abdullah, Nahar Zabun, Rabbi Sikder Nahidul Islam, Ahmed Maizbha Uddin, Islam Mohammad Safiqul, Hasnat Abul
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.
Cancer Epidemiol. 2017 Aug;49:46-52. doi: 10.1016/j.canep.2017.05.005. Epub 2017 May 26.
Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77-3.77, p<0.05) and Pro/Pro mutant homozygosity (adjusted OR=2.92, 95% CI=1.78-4.78, p<0.05) along with the combined genotype (Arg/Pro+Pro/Pro) (adjusted OR=2.70, 95% CI=1.90-3.82, p<0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p<0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42-2.87, p<0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.
迄今为止，尚未有关于孟加拉人群中TP53基因第72密码子（Arg72Pro）和CDH1基因rs16260（-160C<A）与结直肠癌关系的药物遗传学研究报道。因此，本研究的目的是首次确定在孟加拉人群中，TP53基因第72密码子和CDH1基因rs16260的基因多态性是否会增加结直肠癌发生的风险。为了研究这两个单核苷酸多态性（SNP）的关联性，我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对288例结直肠癌患者和295名健康志愿者进行了病例对照研究。我们发现，Arg/Pro杂合性（校正比值比[OR]=2.58，95%可信区间[CI]=1.77-3.77，p<0.05）、Pro/Pro突变纯合性（校正OR=2.92，95%CI=1.78-4.78，p<0.05）以及联合基因型（Arg/Pro+Pro/Pro）（校正OR=2.70，95%CI=1.90-3.82，p<0.05）与结直肠癌易感性之间存在关联增加的风险。对于CDH1基因rs16260多态性，发现C/A杂合性和A/A突变纯合性与结直肠癌风险显著相关（p<0.05），校正OR分别为1.94和2.63。与C/C基因型相比，C/A和A/A的联合基因型也与结直肠癌风险密切相关（校正OR=2.02，95%CI=1.42-2.87，p<0.05）。总之，TP53基因Arg72Pro和CDH1基因rs16260的杂合性、突变纯合性以及两者的组合均会增加孟加拉人群中结直肠癌发生的风险。
