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.

Background: Human papillomavirus infection is the major cause of cervical cancer, but only few cases develop into cancer. Although, HuR (ELAVL1) gene has been implicated in the oncogenesis of certain cancers. However, the correlation between the ELAVL1 gene and the risk of cervical cancer in Tunisian women remains unclear. Therefore, this study investigated the effect of ELAVL1 gene polymorphisms (SNPs) in cervical cancer development.Method: ELAVL1 gene SNPs: ELAVL1 rs12983784 T>C, ELAVL1 rs14394 T>C, ELAVL1 rs74369359 G>T, ELAVL1 rs35986520 G>A, ELAVL1 rs10402477 C>T, ELAVL1 rs12985234 A>G, ELAVL1 rs2042920 T>G, were genotyped by High resolution melting (HRM). SHEsis online software was used to perform linkage disequilibrium (LD) and haplotype analyses.Results: Comparing the cervical cancer patients with healthy control participants, the TC genotype of rs12983784 SNP (P=0.017, OR = 2.78, 95% CI = 1.2~6.45), the GT genotype of the rs74369359 SNP (P=0.004, OR = 9.4, 95% CI = 1.73~16.96) and the CT genotype of the rs10402477 SNP (P=0.002, OR = 5.89, 95% CI = 1.89~18.36) were associated with increased cervical cancer risk. TT genotype of rs12983784 SNP (P=0.005), GG genotype of the rs74369359 SNP (P=0.000) and CC genotype of the rs10402477 SNP (P=0.000) were considered as protective factors against cervical cancer in the Tunisian population.The haplotype analysis of the 7 SNPs of ELAVL1 gene suggested that "C C G G C A G" (P=0.

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 (ORa = 2.81; ORa = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (ORa = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (ORa = 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 (ORa = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (ORa = 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.

Background: Human papillomavirus infection is the major cause of cervical cancer, but only few cases develop into cancer. Although, HuR (ELAVL1) gene has been implicated in the oncogenesis of certain cancers. However, the correlation between the ELAVL1 gene and the risk of cervical cancer in Tunisian women remains unclear. Therefore, this study investigated the effect of ELAVL1 gene polymorphisms (SNPs) in cervical cancer development.Method: ELAVL1 gene SNPs: ELAVL1 rs12983784 T>C, ELAVL1 rs14394 T>C, ELAVL1 rs74369359 G>T, ELAVL1 rs35986520 G>A, ELAVL1 rs10402477 C>T, ELAVL1 rs12985234 A>G, ELAVL1 rs2042920 T>G, were genotyped by High resolution melting (HRM). SHEsis online software was used to perform linkage disequilibrium (LD) and haplotype analyses. Results: Comparing the cervical cancer patients with healthy control participants, the TC genotype of rs12983784 SNP (P=0.017, OR = 2.78, 95% CI = 1.2~6.45), the GT genotype of the rs74369359 SNP (P=0.004, OR = 9.4, 95% CI = 1.73~16.96) and the CT genotype of the rs10402477 SNP (P=0.002, OR = 5.89, 95% CI = 1.89~18.36) were associated with increased cervical cancer risk. TT genotype of rs12983784 SNP (P=0.005), GG genotype of the rs74369359 SNP (P=0.000) and CC genotype of the rs10402477 SNP (P=0.000) were considered as protective factors against cervical cancer in the Tunisian population. The haplotype analysis of the 7 SNPs of ELAVL1 gene suggested that “C C G G C A G” (P=0.02), “T T G G T A T” (P=0.01) and “T T T G C A T” (P=0.002) were a significant risk factor for cervical cancer. However, “TCGACAT” (P=0.04) and “TTGGCAT” (P=0.04) participated in the decrease of cervical cancer disease.The frequency of ELAVL1 haplotype rs10402477-rs2042920 TT was significantly higher in the cases group than in the control group (P=0.0001).Thus, this genotype increases cervical cancer risk among Tunisian women. Conclusion: The results of our study indicated that genetic variants in the ELAVL1 gene might be associated with susceptibility to cervical cancer in the Tunisian population.