Abstract
Objectives: To evaluate association of genetic polymorphisms in GSTM1, T1, and P1 genes with cervical cancer (CC) susceptibility and effect of passive smoking.Methods: The polymorphisms in GSTM1 and T1 were analyzed by multiplex polymerase chain reaction (mPCR) and GSTP1 by PCR - Restriction Fragment Length Polymorphism (PCR-RFLP) in 150 CC cases and 165 healthy controls.Results: CC cases showed significant association with marriage age, parity and hemoglobin level (p<0.0001). GSTM1 (-/-) genotype was prominent among cases (30.0 %) whereas on combined analysis, GSTM1(-/-) / T1(-/-) and GSTM1(-/-) / P1(A/G or G/G) genotypes showed 2.75 and 2.98 times higher susceptibility to CC respectively. Triple combinations of GSTM1 (-/-), T1 (+/+) and P1 (A/G or G/G) genotypes showed significant association (P=0.02) with a 3.04 times risk of developing CC. Further analysis of cervical cancer histological subtypes such as squamous cell carcinoma and adenocarcinoma revealed an association of GSTM1 (-/-), GSTP1 A/G and G/G genotypes in adenocarcinoma cases alone (4.01, 2.25 and 2.40 folds respectively). Out of all the CC cases, passive smokers with GSTM1 (-/-) and GSTP1 (G/G) genotypes showed 4.19 and 2.88 times respectively of increased risk of developing the disease.Conclusions: This study confirms the possible interactions between different GST polymorphisms and passive smoking in cervical cancer cases from North India.
Highlights
Carcinoma of cervix is the second most common cancer among women worldwide[1]
All the 150 cases of cervical cancer were histopathologically confirmed in which 7.3% (11 out of 150) were adenocarcinoma and remaining 92.7% (139 out of 150) were squamous cell carcinoma
Squamous cell carcinoma was further differentiated according to cell types into well differentiated (37.4%), moderately differentiated (33.8%) and poorly differentiated (5.8%), while 23.0% cases had no differentiation specified in histopathological report
Summary
Carcinoma of cervix is the second most common cancer among women worldwide[1]. In India, about 130,000 new cases are diagnosed each year out of which >70,000 deaths occur annually[2]. Poppe et al[10] have shown immunohistochemically that in smokers there is a decrease in Langerhans cells as well as helper-T lymphocytes in the squamous epithelia of uterine cervix transformation zone which is the start site of cervical cancer. Another cause responsible for pathogenesis of cervical cancer may be the direct contact of seminal fluid of smoking sex partners with the mucus membrane of cervix during sexual intercourse[11]. Active smokers are those who inhale smoke directly but passive smokers do not smoke themselves but inhale it from others smoking around them
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