https://orcid.org/0000-0003-3747-1482
Abstract
Purpose
Fat mass and obesity-associated protein (FTO) and AlkB homolog 1 (ALKBH1) are m6A demethylases that have been demonstrated to be associated with the overall survival of patients with gastric cancer (GC). This study investigates the influence of genetic variants of FTO and ALKBH1 on susceptibility to GC.
Patients and Methods
Potentially functional single nucleotide polymorphisms (SNPs) of FTO and ALKBH1 were genotyped in 419 patients with GC and 569 healthy controls by Kompetitive allele-specific PCR.
Results
The AG and AG/AA variants of FTO rs2287142 were significantly associated with a decreased GC risk (for AG/AA vs GG: adjusted OR = 0.73, p = 0.020). The GA and GA/GG variants of ALKBH1 rs1076496 were closely correlated with an increased risk of GC in people aged ≥ 55 years (for GA/GG vs AA: adjusted OR = 1.51, p = 0.041) but showed a decreasing tendency of risk of GC in people aged <55 years (adjusted OR = 0.85, p = 0.444). FTO rs2287142 and ALKBH1 rs1076496 conformed to the principle of a dominant model. FTO haplotype rs1421091-rs1421092-rs2287142-rs9939609 CTAT was closely associated with a lower risk of total GC (adjusted OR = 0.62, p = 0.023), while CTGA was linked with an increased risk of intestinal GC (adjusted OR = 2.51, p = 0.005). ALKBH1 rs1048147-rs1076496-rs11159286 CAC haplotype was significantly associated with a decreased risk of GC in people aged ≥ 55 years (adjusted OR = 0.41, p = 0.008). The FTO rs2287142-rs9939609 AG/AA-TT combination was associated with a decreased risk of GC only in the presence of rs1421091 TC/TT (adjusted OR = 0.70, p = 0.047), demonstrating that these FTO SNPs might have a cooperative effect on susceptibility to GC.
Conclusion
FTO and ALKBH1 SNPs may have predictive value in evaluating susceptibility to GC with differing age or Lauren classification.
Abbreviations
ALKBH1, alkB homolog 1; CI, confidence interval; ESE/ESS, exonic splicing enhancer/silencer; FTO, fat mass and obesity-associated protein; GC, gastric cancer; LD, linkage disequilibrium; m6A, N6-methyladenosine; OR, odds ratio; SNP, single nucleotide polymorphism; TFBS, transcriptional factor binding site.
Data Sharing Statement
The datasets used or analyzed in the current study are available from the corresponding author on reasonable request.
Ethics Approval and Informed Consent
This study was approved by the Ethics Committee of Sun Yat-sen University Cancer Center (Guangzhou, China) (approval NO. G2022-002-01). Written informed consent was provided by all participants at their first visit. All experiments were performed in accordance with the guidelines stated in the Declaration of Helsinki.
Consent for Publication
The purpose of this study was well informed to the all participants and written informed consent was obtained from the all participants for publication of this report.
Acknowledgments
We are grateful to the individuals for their participation in this study.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.