Senthilkumar K P, Thirumurugan R
Mol Biol Rep. 2014 Sep;41(9):5635-44. doi: 10.1007/s11033-014-3433-x.
Tobacco use and environmental air pollution are the established etiological factors in head and neck cancer (HNC) progression. Nevertheless, not all the inhabitants with high usage of tobacco from the same polluted locality are suffering with HNC and this is due to the existence of factors like inter-individual genetic polymorphisms, life time exposure to tobacco and the rate of xenobiotic metabolism enzyme (XME) activity. The present study investigates the polymorphic genotypes of the most important XME, glutathione-S-transferase Mu 1 (GST M1) and Theta 1 (GST T1) as the risk modulator to HNC among tobacco-habituated inhabitants of Saurashtra in Gujarat, a region in western India. A population based case–control study was done in 252 HNC patients and 504 healthy controls. Blood samples were collected from the subjects and investigated for polymorphic genotypes of GST M1 and GST T1. Estimation of the odds of risks was done by logistic regressions. Among the subjects with high usage of tobacco, M1 not null-T1 null genotypes presence was found as risk reducing factor to HNC with 0.334 folds (95 % CI; 0.170-0.659). The presence of M1 null-T1 not null genotypes was found with susceptibility to HNC among the subjects with no habit of tobacco chewing, adjusted odds ratio (AOR) 3.170 (1.128-8.913) and no habit of smoking, AOR of 2.544 (1.094-5.963). The present study reveals the finding of significantly increased risk to HNC by interactions of GST M1 null-GST T1 not null polymorphic genotypes among the subjects with nil or less tobacco usage shed some light for the insights of biomarker application in early detection of HNC.
烟草使用和环境空气污染是头颈癌(HNC)进展中已确定的病因。然而,并非来自同一污染地区的所有高烟草使用率居民都患有头颈癌,这是由于个体间基因多态性、终生烟草暴露以及异生物质代谢酶(XME)活性等因素的存在。本研究调查了印度西部古吉拉特邦索拉什特拉地区有烟草使用习惯的居民中,最重要的XME即谷胱甘肽-S-转移酶Mu 1(GST M1)和Theta 1(GST T1)的多态基因型作为头颈癌风险调节因子的情况。对252名头颈癌患者和504名健康对照进行了一项基于人群的病例对照研究。从受试者采集血样,检测GST M1和GST T1的多态基因型。通过逻辑回归估计风险几率。在高烟草使用率的受试者中,发现M1非缺失-T1缺失基因型的存在是头颈癌的风险降低因素,风险降低倍数为0.334(95%置信区间:0.170 - 0.659)。在不咀嚼烟草的受试者中,发现M1缺失-T1非缺失基因型的存在与头颈癌易感性相关,调整优势比(AOR)为3.170(1.128 - 8.913);在不吸烟的受试者中,AOR为2.544(1.094 - 5.963)。本研究揭示,在烟草使用量极少或无烟草使用的受试者中,GST M1缺失-GST T1非缺失多态基因型的相互作用显著增加了头颈癌风险,这为生物标志物在头颈癌早期检测中的应用提供了一些见解。