The Journal of Practical Medicine >

2023 , Vol. 39 >Issue 21: 2834 - 2842

DOI: https://doi.org/10.3969/j.issn.1006-5725.2023.21.024

Medical Examination and Clinical Diagnosis

Association of genetic variants of m6A binding protein with the risk of gastric cancer

  • Xinyuan LU ,
  • Yanlu FENG ,
  • Jie LI ,
  • Siyi XU ,
  • Chengyun LI ,
  • Tong LIU ,
  • Xinhua WANG ,
  • Geyu LIANG
Expand
  • Key Laboratory of Environmental Medicine Engineering，Ministry of Education； School of Public Health，Southeast University，Nanjing，210009，China

Received date: 2023-07-12

  Online published: 2023-12-19

Fold

Abstract

Objective To investigate the association between single nucleotide polymorphisms （SNPs） of YTHDF1 rs6011668， HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer. Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected. The candidate SNPs were genotyped using Hi?SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing； the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression. Multifactorial logistic regression and Risk Score （RS） model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer. Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers （95% CI：1.128 ~ 8.382， P = 0.028）， and 2.961 times higher risk than CC/TC genotypes carriers （95% CI：1.091 ~ 8.033， P = 0.033）. Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non?tea drinkers， pickled food eaters and fried food eaters（P < 0.05）. In addition， TT genotype carriers had the increased risk of gastric cancer infiltration， lymph node metastasis， distal metastasis and intermediate to advanced stages（P < 0.05）. The RS of the case and control groups were calculated by combining environmental and genetic factors. The higher the RS score， the higher the risk of gastric cancer was found in the RS quartile groups. Compared with the RS < Q25 group， the risk of gastric cancer in the Q25 < RS < Q50， Q50 < RS < Q75 and RS ≥ Q75 groups was 3.090， 9.731 and 19.949， respectively. Conclusion The YTHDF1 rs6011668 mutant genotype may be associated with an increased risk and clinical progression of gastric cancer， and combining environmental and genetic factors could better assess the risk of gastric cancer.

Key words： gastric cancer; m6A; YTHDF1; HNRNPA2B1; single nucleotide polymorphism

Cite this article

Xinyuan LU , Yanlu FENG , Jie LI , Siyi XU , Chengyun LI , Tong LIU , Xinhua WANG , Geyu LIANG . Association of genetic variants of m6A binding protein with the risk of gastric cancer[J]. The Journal of Practical Medicine, 2023 , 39(21) : 2834 -2842 . DOI: 10.3969/j.issn.1006-5725.2023.21.024

References

1 SUNG H， FERLAY J， SIEGEL R L， et al. Global Cancer Statistics 2020： GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries［J］. CA Cancer J Clin， 2021，71（3）：209-249.
2 MACHLOWSKA J， BAJ J， SITARZ M， et al. Gastric Cancer： Epidemiology， Risk Factors， Classification， Genomic Characteristics and Treatment Strategies［J］. Int J Mol Sci， 2020， 21（11）：4012.
3 OLIVEIRA C， PINHEIRO H， FIGUEIREDO J， et al. Familial gastric cancer： genetic susceptibility， pathology， and implications for management［J］. Lancet Oncol， 2015，16（2）： e60-70.
4 CAO G， LI H B， YIN Z， et al. Recent advances in dynamic m6A RNA modification［J］. Open Biol， 2016， 6（4）：160003.
5 MEYER K D， JAFFREY S R. Rethinking m6A Readers， Writers， and Erasers［J］. Annu Rev Cell Dev Biol， 2017， 33：319-342.
6 LIU T， WEI Q， JIN J， et al. The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation［J］. Nucleic Acids Res， 2020， 48（7）：3816-3831.
7 LI Q， NI Y， ZHANG L， et al. HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation［J］. Signal Transduct Target Ther， 2021， 6（1）：76.
8 ALARCON C R， GOODARZI H， LEE H， et al. HNRNPA2B1 Is a Mediator of m （6）A-Dependent Nuclear RNA Processing Events ［J］. Cell， 2015， 162（6）： 1299-1308.
9 AN Y， DUAN H. The role of m6A RNA methylation in cancer metabolism［J］. Mol Cancer， 2022， 21（1）：14.
10 HAWKINS S F C， GUEST P C. Multiplex Single Nucleotide Polymorphism Analyses［J］. Methods Mol Biol， 2017，1546：143-148.
11 SAEKI N， ONO H， SAKAMOTOO H， et al. Genetic factors related to gastric cancer susceptibility identified using a genome-wide association study［J］. Cancer Sci， 2013，104（1）：1-8.
12 LIU J， CHENG J， LI L， et al. YTHDF1 gene polymorphisms and neuroblastoma susceptibility in Chinese children： an eight-center case-control study［J］. J Cancer， 2021，12（8）：2465-2471.
13 LUO Z， LI G， WANG M， et al. YTHDF1 rs6090311 A > G polymorphism reduces Hepatoblastoma risk： Evidence from a seven-center case-control study［J］. J Cancer， 2020， 11（17）：5129-5134.
14 LIU Y， LIN H， HUA R X， et al. Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility： A five-center case-control study［J］. J Clin Lab Anal， 2021，35（8）： e23875.
15 LI Y， ZHOU D， LIU Q， et al. Gene Polymorphisms of m6A Erasers FTO and ALKBH1 Associated with Susceptibility to Gastric Cancer［J］. Pharmgenomics Pers Med， 2022，15：547-559.
16 WANG X， GUAN D， WANG D， et al. Genetic variants in m6A regulators are associated with gastric cancer risk［J］. Arch Toxicol， 2021，95（3）：1081-1088.
17 WANG H， LUO Q， KANG J， et al. YTHDF1 Aggravates the Progression of Cervical Cancer Through m6A-Mediated Up-Regulation of RANBP2［J］. Front Oncol， 2021，11：650383.
18 YAO X， LI W， LI L， et al. YTHDF1 upregulation mediates hypoxia-dependent breast cancer growth and metastasis through regulating PKM2 to affect glycolysis［J］. Cell Death Dis， 2022，13（3）：258.
19 HAO L， WANG J M， LIU B Q， et al. m6A-YTHDF1-mediated TRIM29 upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells［J］. Biochim Biophys Acta Mol Cell Res， 2021，1868（1）：118878.
20 WANG S， GAO S， ZENG Y， et al. N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer［J］. Gastroenterology， 2022，162（4）：1183-1196.
21 LIU T， YANG S， CHENG Y P， et al. The N6-Methyladenosine （m6A） Methylation Gene YTHDF1 Reveals a Potential Diagnostic Role for Gastric Cancer［J］. Cancer Manag Res， 2020，12：11953-11964.
22 BAI X， WONG C C， PAN Y， et al. Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells［J］. J Immunother Cancer， 2022，10（2）： e003663.
23 YOU Q， WANG F， DU R， et al.m6A Reader YTHDF1-Targeting Engineered Small Extracellular Vesicles for Gastric Cancer Therapy via Epigenetic and Immune Regulation［J］. Adv Mater， 2023，35（8）： e2204910.
24 JIANG X， LIU B， NIE Z， et al. The role of m6A modification in the biological functions and diseases［J］. Signal Transduct Target Ther， 2021， 6（1）：74.
25 HU L， LIU S， YAO H， et al. Identification of a novel heterogeneous nuclear ribonucleoprotein A2B1 （hnRNPA2B1） ligand that disrupts HnRNPA2B1/nucleic acid interactions to inhibit the MDMX-p53 axis in gastric cancer［J］. Pharmacol Res， 2023，189：106696.
26 PENG W Z， ZHAO J， LIU X， et al. hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression［J］. Cancer Cell Int， 2021，21（1）：281.
27 BOURAS E， TSILIDIS K K， TRIGGI M， et al. Diet and Risk of Gastric Cancer： An Umbrella Review［J］. Nutrients， 2022， 14（9）：1764.
28 LI Y， ESHAK E S， SHIRA K， et al. Alcohol Consumption and Risk of Gastric Cancer： The Japan Collaborative Cohort Study［J］. J Epidemiol， 2021， 31（1）：30-36.
29 REN J S， KAMANGAR F， FORMAN D， et al. Pickled food and risk of gastric cancer--a systematic review and meta-analysis of English and Chinese literature［J］. Cancer Epidemiol Biomarkers Prev， 2012， 21（6）：905-915.
30 MARTIMIANAKI G， ALICANDRO G， PELUCCHI C， et al. Tea consumption and gastric cancer： a pooled analysis from the Stomach cancer Pooling （StoP） Project consortium［J］. Br J Cancer， 2022， 127（4）：726-734.
Options
Outlines

/

〈 〉