Islam Mohammad Safiqul, Mostofa A G M, Ahmed Maizbha Uddin, Bin Sayeed Muhammad Shahdaat, Hassan Md Rajib, Hasnat Abul
Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali, 3814, Bangladesh.
Tumour Biol. 2014 Feb;35(2):1671-8. doi: 10.1007/s13277-013-1230-0. Epub 2013 Oct 2.
The rate of direct smoking, second hand smoking, and smokeless tobacco users as well as the amount of environmental pollutant like polycyclic aromatic hydrocarons is increasing in Bangladesh. Therefore, the prevalence of lung cancer is increasing day by day. To the best of our knowledge, no pharmacogentic study of CYP3A4, CYP3A5 genes has been reported on Bangladeshi population relating those with lung cancer. The present study was conducted to determine the association of CYP3A4, CYP3A5 gene polymorphisms and tobacco smoking in the development of lung cancer in Bangladeshi population. A case-control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants-CYP3A41B, CYP3A53, and CYP3A56 using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Risk of lung cancer was estimated as odds ratio (OR) and 95 % confidence interval (CI) using unconditional logistic regression models. The variant allele frequencies for CYP3A41B (*1A/*1B + *1B/1B) were 2.83 % and 0.86 % and that of CYP3A53 (*1A/*3 + 3/3) were 88.68 % and 85.34 % in cases and controls, respectively. Individual carrying at least one variant allele of CYP3A41B (CYP3A41A/1B + 1B/1B) has a 3.35 times more risk (OR = 3.35, 95 % Cl = 0.34-32.71, p = 0.271) for developing lung cancer whereas individual carrying at least one variant allele of CYP3A5 (CYP3A51A/3 + 3/3) has a 1.26 times more risk (OR = 1.35, 95 % Cl = 0.61-2.97) and both are statistically non-significant (p > 0.05). CYP3A56 was absent in the study population. No association of lung cancer with the mentioned polymorphisms was found both in heavy and light smokers. In the cases of all three major types of lung cancer-squamous cell carcinoma, adenocarcinoma, and small cell carcinoma-significantly strong relationships (p ˂ 0.05) have been found. To confirm the association of lung cancer with the mentioned polymorphisms, large number volunteers (patients and controls) will be required.
在孟加拉国，直接吸烟者、二手吸烟者、无烟烟草使用者的比例以及多环芳烃等环境污染物的含量都在上升。因此，肺癌的患病率日益增加。据我们所知，尚未有关于孟加拉人群中CYP3A4、CYP3A5基因与肺癌相关性的药物遗传学研究报道。本研究旨在确定孟加拉人群中CYP3A4、CYP3A5基因多态性与吸烟在肺癌发生中的关联。采用聚合酶链反应-限制性片段长度多态性方法，对106例肺癌患者和116例对照进行病例对照研究，以检测三个等位基因变体——CYP3A41B、CYP3A53和CYP3A56。使用无条件逻辑回归模型，将肺癌风险估计为比值比（OR）和95%置信区间（CI）。病例组和对照组中，CYP3A41B（*1A/*1B + *1B/1B）的变异等位基因频率分别为2.83%和0.86%，CYP3A53（*1A/*3 + 3/3）的变异等位基因频率分别为88.68%和85.34%。携带至少一个CYP3A41B变异等位基因（CYP3A41A/1B + 1B/1B）的个体患肺癌的风险高3.35倍（OR = 3.35，95% Cl = 0.34 - 32.71，p = 0.271），而携带至少一个CYP3A5变异等位基因（CYP3A51A/3 + 3/3）的个体患肺癌的风险高1.26倍（OR = 1.35，95% Cl = 0.61 - 2.97），两者均无统计学意义（p > 0.05）。研究人群中未发现CYP3A56。在重度和轻度吸烟者中，均未发现肺癌与上述多态性之间存在关联。在所有三种主要类型的肺癌——鳞状细胞癌、腺癌和小细胞癌中，均发现了显著的强相关性（p ˂ 0.05）。为了证实肺癌与上述多态性之间的关联，需要大量的志愿者（患者和对照）。
