基因多态性与宫颈癌易感性关联的评估：一项病例对照研究及荟萃分析。

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

作者信息

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

机构信息

Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Sonapur, 3814, Noakhali, Bangladesh.

Laboratory of Pharmacogenomics and Molecular Biology, Department of Pharmacy, Noakhali Science and Technology University, Sonapur, 3814, Noakhali, Bangladesh.

出版信息

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

DOI:10.1016/j.heliyon.2023.e17712

PMID:37483787

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10359826/

Abstract

BACKGROUND

Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the 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 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 ( > 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, r = 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 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 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

摘要

背景

宫颈癌（CC）是孟加拉国第二常见的女性恶性肿瘤类型。据报道，该基因的多态性在不同人群中与宫颈癌相关。本病例对照研究及荟萃分析旨在评估rs4646903和rs1048943多态性与宫颈癌易感性的关系。

方法

共招募了185例宫颈癌患者和220例对照，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术进行基因分型。此外，纳入42项符合条件的研究（24项关于rs4646903，18项关于rs1048943）进行荟萃分析，使用RevMan 5.3和基于网络的MetaGenyo工具。

结果

在所有关联模型中，即加性模型1、加性模型2、显性模型、隐性模型、超显性模型和等位基因模型中，rs4646903多态性与宫颈癌显著相关（相应的比值比[OR]分别为2.41、4.75、2.67、3.61、2.13和2.44，95%置信区间[CI]分别为1.55 - 3.76、1.81 - 12.45、1.75 - 4.07、1.39 - 9.35、1.38 - 3.30和1.71 - 3.48）。相反，rs1048943与宫颈癌无关联（P > 0.05）。单倍型分析显示，AT和AC单倍型分别显著降低（OR = 0.45）和增加（OR = 4.86）宫颈癌风险，且单核苷酸多态性处于强连锁不平衡状态（D' = 0.912，r = 0.448）。此外，有避孕史且服用避孕药超过5年的rs4646903携带者患宫颈癌的风险增加（OR = 2.39，OR = 3.05）。另外，年龄大于40岁（OR = 0.44）、首胎年龄小于等于18岁（OR = 3.45）以及有避孕史（OR = 2.18）的rs1048943携带者与宫颈癌显著相关。我们的荟萃分析发现，对于rs4646903，在白种人中的共显性模型1（COD 1）、共显性模型2（COD 2）、共显性模型3（COD 3）、显性模型（DM）、隐性模型（RM）和等位基因模型（AM）以及在总体人群中的超显性模型（OD）与宫颈癌风险升高相关，而rs1048943在某些遗传模型中在总体人群、白种人和亚洲人中也与宫颈癌相关。