Impact of interleukin-32 germ-line rs28372698 and intronic rs12934561 polymorphisms on cancer development: A systematic review and meta-analysis

Sarah Jafrin; Md Abdul Aziz; Mohammad Safiqul Islam

doi:10.1016/j.intimp.2021.107964

Impact of interleukin-32 germ-line rs28372698 and intronic rs12934561 polymorphisms on cancer development: A systematic review and meta-analysis

Int Immunopharmacol. 2021 Oct:99:107964. doi: 10.1016/j.intimp.2021.107964. Epub 2021 Jul 13.

Authors

Sarah Jafrin¹, Md Abdul Aziz¹, Mohammad Safiqul Islam²

Affiliations

¹ 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.
² 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. Electronic address: research_safiq@yahoo.com.

PMID: 34271417
DOI: 10.1016/j.intimp.2021.107964

Abstract

Objective: The pro-inflammatory cytokine IL-32 has high susceptibility to develop cancer. But no previous meta-analysis was done to provide firm evidence. This systematic review and meta-analysis was designed to evaluate the association of IL-32 gene polymorphisms (rs28372698 and rs12934561) with cancer.

Method: Eligible studies were selected using authentic databases searching from January 2013 to January 2021. Demographic data and genotypic information were extracted and organized from the selected studies. Review Manager (RevMan) version 5.4 was used to perform data analysis and data arrangement for meta-analysis.

Results: A total of seven studies with 3395 patients and 3781 controls were included in this study. IL-32 rs28372698 polymorphism implied that mutant allele (TT) carriers had a significantly higher risk of cancer (OR = 1.43, p = 0.032). Codominant 3, recessive and allele models also showed 1.36-, 1.38- and 1.11-fold increased risk, respectively (p < 0.05). Besides, the Asian population showed a significantly increased risk in codominant 2 (OR = 1.74), codominant 3 (OR = 1.78), recessive (OR = 1.76) and allele model (OR = 1.16). IL-32 rs12934561 showed significantly reduced cancer risk in codominant 1 (OR = 0.66. p = 0.035), codominant 2 (OR = 0.76, p = 0.007), and dominant model (OR = 0.72, p = 0.012). After subgroup analysis, an association of rs12934561 was found in Asians (codominant 1: OR = 0.54, p = 7.28 × 10^-8; codominant 2: OR = 1.40, p = 0.019; codominant 3: OR = 0.76, p = 0.0006; dominant model: OR = 0.64, p = 1.12 × 10^-5; overdominant model: OR = 0.64, p = 3.92 × 10^-7) but not in Caucasians. After stratifying with the control source, a significant (p < 0.05) association of rs28372698 and rs12934561 was found with cancer in population-based controls. No publication bias was found, and the outcome of this meta-analysis was not influenced by any individual study confirmed from sensitivity analysis. Moreover, trial sequential analysis (TSA) established a link between rs28372698 and rs12934561 polymorphisms and cancer.

Conclusion: The outcome of this meta-analysis revealed that IL-32 rs28372698 and rs12934561 polymorphisms are associated with cancer. Moreover, the Asian dynasty had a significant association compared to Caucasians.

Keywords: Cancer; IL-32; Meta-analysis; Polymorphism; rs12934561; rs28372698.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Animals
Antibody Diversity
Carcinogenesis / genetics*
Humans
Interleukins / genetics*
Neoplasms / genetics*
Polymorphism, Genetic

Substances

IL32 protein, human
Interleukins