Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis

Md Abdul Barek; Mohammad Anwarul Basher; Md Abdul Aziz; Md Shafiul Hossen; Nusrat Jahan; Nahida Afroz; Mobashera Begum; Sarah Jafrin; Mohammad Sarowar Uddin; Md Shalahuddin Millat; Md Mahmudul Hoque; Mohammad Safiqul Islam

doi:10.1016/j.heliyon.2023.e17712

Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis

Heliyon. 2023 Jul 4;9(7):e17712. doi: 10.1016/j.heliyon.2023.e17712. eCollection 2023 Jul.

Authors

Md Abdul Barek^{1

2}, Mohammad Anwarul Basher¹, Md Abdul Aziz^{1

2}, Md Shafiul Hossen^{1

2}, Nusrat Jahan^{1

2}, Nahida Afroz^{1

2}, Mobashera Begum^{1

2}, Sarah Jafrin^{1

2}, Mohammad Sarowar Uddin^{1

2}, Md Shalahuddin Millat^{1

2}, Md Mahmudul Hoque³, Mohammad Safiqul Islam^{1

2}

Affiliations

¹ Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Sonapur, 3814, Noakhali, Bangladesh.
² Laboratory of Pharmacogenomics and Molecular Biology, Department of Pharmacy, Noakhali Science and Technology University, Sonapur, 3814, Noakhali, Bangladesh.
³ Department of Pharmacy, National Institute of Cancer Research and Hospital, Mohakhali, Dhaka, 1212, Bangladesh.

Abstract

Background: Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC.

Methods: A total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used.

Results: The rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55-3.76, 1.81-12.45, 1.75-4.07, 1.39-9.35, 1.38-3.30, and 1.71-3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D' = 0.912, r² = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models.

Conclusion: Our case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

Keywords: CYP1A1; Contraceptives; Haplotype; PCR-RFLP; rs1048943; rs4646903.