Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population

Abstract

Background: Host genetic characteristics and environmental factors interactions may play a crucial role in cervical carcinogenesis. We investigated the impact of functional genetic variants of four xenobiotic-metabolizing genes (AhR, CYP1A1, GSTM1, and GSTT1) on cervical cancer development in Tunisian women. Methods:The AhR gene polymorphism was analyzed using the tetra-primer ARMS-PCR, whereas the CYP1A1 polymorphism genotypes were identified by PCR-RFLP. A multiplex ligation-dependent polymerase chain reaction approach was applied for the analysis of GSTM1 and GSTT1 polymorphisms. Results:The homozygous A/A genotype of the AhR gene (rs2066853) and the heterozygous T/C genotype of the CYP1A1 SNP (CYP1A1-MspI) appeared to be associated with an increased risk of cervical tumorigenesis (OR a = 2.81; OR a = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (OR a = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (OR a = 1.18; p = 0.784). Considering the combined effect, we noted a significantly higher association with cancer risk for individuals with at least two high-risk genotypes of CYP1A1/GSTT1 (OR a = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (OR a = 11.3) and individuals with at least two high-risk genotypes of CYP1A1/GSTM1/GSTT1/AhR exploitation low-risk genotype as a reference. Conclusion:This study indicated that the single-gene contribution and the combined effect of xenobioticmetabolizing gene polymorphisms (AhR, CYP1A1-MspI, GSTM1, and GSTT1) may have a considerable association with increased cervical cancer risk.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes

“…Our investigation did not reveal significant associations for the CYP1A1 gene. There is at least one study able to associate CYP1A1 with susceptibility to HPV infection [100], and all of our variants (T5639C, A4889G, and C4887A) were found to be involved in cervical cancer in other studies [101][102][103][104][105][106][107][108]. Similar to our case, the A4889G variant was not associated with cervical cancer in an Indian population [108]; still, our results seem to not fit the trend of most studies.…”