Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men

Abstract

The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.

Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region

“…Both GSTM1 and GSTT1 gene exhibit an inherited homozygous deletion polymorphism (null genotype), which has been associated with the loss of enzymatic activity and increased vulnerability to cytogenetic damage (Norppa, 2004). As a result of decreased efficiency in protection against carcinogens, the individuals with homozygous deletion polymorphism are considered to be at an increased risk for malignancies (Hayes et al, 2005;Mcllwain et al, 2006;Singh et al, 2010;Ihsan et al, 2011). Many studies have been published on the association of CYP1A1 and GSTM1 polymorphisms and lung cancer susceptibility with inconsistent findings.…”

“…Many studies have been published on the association of CYP1A1 and GSTM1 polymorphisms and lung cancer susceptibility with inconsistent findings. Some of the studies showed the relationship between the polymorphisms of GSTM1 and CYP1A1 Ile/Val genotype (Singh et al, 2010;Ihsan et al, 2011) but other results are contradictory (Le Marchand et al, 1998;London et al, 2000). However, some data of Chinese Han population (Shi et al, 2008) and little data on Mongolian population are still available.…”

Meta-analysis of the CYP1A2 -163C＞A Polymorphism and Lung Cancer Risk

“…After deleted duplicate and non-relevant studies, finally seven casecontrol studies (Gemignani et al, 2007;Osawa et al, 2007;Zienolddiny et al, 2008;Aldrich et al, 2009;B'Chir et al, 2009;Singh et al, 2010;Gervasini et al, 2013) and one nested case-control study (Pavanello et al, 2012) involving 1675 lung cancer patients and 2393 controls were included.…”

Association of CYP2E1 and NAT2 Polymorphisms with Lung Cancer Susceptibility among Mongolian and Han Populations in the Inner Mongolian Region

“…Besides, many studies aim at exploring the gene-gene interaction among metabolic enzyme genes (Singh et al, 2011;Ying et al, 2013;Gao et al, 2014), but interaction between CYP2E1 and NAT2 polymorphism has not been reported.…”