Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Mohamed I Elsalahaty; Samar Sami Alkafaas; Aya O Bashir; Khaled A El-Tarabily; Mohamed T El-Saadony; Eman H Yousef

doi:10.3389/fgene.2024.1302527

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Front Genet. 2024 Feb 28:15:1302527. doi: 10.3389/fgene.2024.1302527. eCollection 2024.

Authors

Mohamed I Elsalahaty^#¹, Samar Sami Alkafaas^#², Aya O Bashir^#³, Khaled A El-Tarabily⁴, Mohamed T El-Saadony⁵, Eman H Yousef^#⁶

Affiliations

¹ Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
² Molecular Cell Biology Unit, Division of Biochemistry, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
³ Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
⁴ Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
⁵ Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
⁶ Department of Biochemistry, Faculty of Pharmacy, Horus University-Egypt, Damietta, Egypt.

^# Contributed equally.

Abstract

Lung cancer is a crucial global issue, with more than one million deaths annually. While smoking is considered the main etiology of the disease, several genetic variants are associated with it. Alterations in vitamin D pathway genes have also been studied in regards to lung cancer, but the findings have been inconclusive. We here present a systematic review and meta-analysis of seven genes in this pathway: CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP3A5, GC, and VDR. Four databases (PubMed, Scopus, Cochrane Library, and Web of Science (WOS) databases) were searched. From these, 16 eligible case-control studies comprising 6,206 lung cancer cases and 7,272 health controls were obtained. These studies were subjected to comprehensive data extraction and quality scoring, and the pooled odds ratio with a 95% confidence interval was calculated to estimate the effect of each variant along with heterogeneity analysis and a risk of bias assessment. Our meta-analysis revealed an association between CYP3A4 (rs2740574) and lung cancer in the allelic, heterozygous, and dominant models. In addition, both VDR (Fok1: rs2228570) and VDR (Cdx-2: rs11568820) displayed a protective role in lung cancer development in the heterozygous and dominant models. Furthermore, VDR (Taq1: rs731236) showed a decreased risk of lung cancer in the allelic, homozygous, and recessive models. Similarly, VDR (BsmI: rs1544410) had a positive effect on lung cancer risk when subjected to allelic and recessive models. Our meta-analysis revealed the lack of association of CYP2R1 (rs10741657), CYP27B1 (rs3782130), CYP27B1 (rs10877012), CYP24A1 (rs6068816), CYP24A1 (rs4809960), CYP3A5 (rs776746), GC (rs7041), GC (rs4588), and VDR (ApaI: rs7975232) with lung cancer. Our work revealed that CYP3A4 (rs2740574) can represent an independent risk factor for lung cancer. This conclusion can aid better personalized medicine for lung cancer management, while further assessment for genetic variants of CYP3A4, CYP27B1, CYP24A1, GC, and VDR is still required to address more robust evidence.

Keywords: gene variants; lung cancer; polymorphism; vitamin D; vitamin D receptor.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This review was funded by the Abu Dhabi Award for Research Excellence, Department of Education and Knowledge (Grant #: 21S105) to KE-T, and by UAEU Program for Advanced Research (UPAR; Grant #: 12S169) to KE-T.