Singh Hariom, Sachan Rekha, Devi S, Pandey Sachchida N, Mittal B
Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Am J Obstet Gynecol. 2008 Mar;198(3):303.e1-6. doi: 10.1016/j.ajog.2007.09.046. Epub 2008 Feb 21.
The objective of the study was to evaluate the influence of genetic polymorphisms of GSTM1, GSTT1, and GSTM3 on the susceptibility of cervical cancer.
Blood samples from 150 women with biopsy-confirmed cervical cancer and 168 healthy controls were analyzed by multiplex polymerase chain reaction (PCR) to detect the presence or absence of GSTM1 and GSTT1. Insertion/deletion polymorphism in intron 6 of GSTM3 was determined by PCR.
The frequencies of homozygous GSTM1 null and GSTT1 null genotypes were found to be significantly higher in cancer patients as compared with healthy controls (P = .009, odds ratio [OR] 1.52, 95% confidence interval [CI], 1.1 to 2.0 and P = .0004, OR 2.4, 95% CI: 1.4 to 4.0, respectively). The AB genotype of GSTM3 also conferred higher risk of cancer (P = .053, OR 1.64, 95% CI, 1.0 to 2.6). However, no significant association of at-risk genotypes was observed with any stages of cervical cancer. Interactions among GSTM1 null, GSTT1 null, and AB genotype of GSTM3 resulted in additive predictive risks of cervical cancer. In case-only analysis, carriers of the AA genotype of GSTM3 among tobacco users were at elevated risk of cervical cancer (P = .024, OR 2.1, 95% CI, 1.0 to 4.1) as compared with AB and BB genotypes.
GSTM1 null, GSTT1 null, and GSTM3AB genotypes may confer higher susceptibility to cervical cancer and cancer risk because at-risk genotypes are additive. Tobacco usage by carriers of GSTM3AA has enhanced the risk of cervical cancer as compared with nonusers.
本研究的目的是评估谷胱甘肽S-转移酶M1（GSTM1）、谷胱甘肽S-转移酶T1（GSTT1）和谷胱甘肽S-转移酶M3（GSTM3）的基因多态性对宫颈癌易感性的影响。
采用多重聚合酶链反应（PCR）对150例经活检确诊的宫颈癌女性患者和168例健康对照者的血样进行分析，以检测GSTM1和GSTT1的有无。通过PCR确定GSTM3第6内含子的插入/缺失多态性。
与健康对照者相比，癌症患者中纯合子GSTM1缺失和GSTT1缺失基因型的频率显著更高（P = 0.009，优势比[OR] 1.52，95%置信区间[CI]，1.1至2.0；P = 0.0004，OR 2.4，95% CI：1.4至4.0）。GSTM3的AB基因型也赋予了更高的癌症风险（P = 0.053，OR 1.64，95% CI，1.0至2.6）。然而，未观察到风险基因型与宫颈癌的任何阶段有显著关联。GSTM1缺失、GSTT1缺失和GSTM3的AB基因型之间的相互作用导致了宫颈癌的累加预测风险。在仅病例分析中，与AB和BB基因型相比，烟草使用者中GSTM3的AA基因型携带者患宫颈癌的风险升高（P = 0.024，OR 2.1，95% CI，1.0至4.1）。
GSTM1缺失、GSTT1缺失和GSTM3AB基因型可能赋予更高的宫颈癌易感性和癌症风险，因为风险基因型具有累加性。与非使用者相比，GSTM3AA携带者吸烟增加了患宫颈癌的风险。
