目的:分析谷胱甘肽过氧化酶4(GPX4)基因单核苷酸多态性(SNP)rs2074452与非贲门胃癌变的关联性。方法:采用病例-对照的方法,收集525例非贲门胃癌患者和506例正常体检者,采用血清学方法检测正常对照中幽门螺杆菌(H.pylori)的感染情况。采用PCR-RFLP法检测GPX4 rs2074452的基因型分布,采用非条件性Logistic回归计算其基因型和等位基因频率,并分析其与H.pylori感染及非贲门胃癌发病风险的关联。结果:rs2074452与H.pylori感染风险无关联,与非贲门胃癌发病风险相关。在隐性模型中,与CC+CT基因型相比,TT基因型降低了非贲门胃癌的发病风险(OR=0.214,95% CI: 0.061-0.756)。结论:GPX4 rs2074452的TT基因型可能是非贲门胃癌发病的保护因素。
Objective: To analyze the relationship between single nucleotide polymorphism (SNP) rs2074452 of glutathione peroxidase 4 (GPX4) gene and non-cardia gastric cancer. Methods: Using a case-control approach, 525 patients with non-cardia gastric cancer and 506 normal examiners were collected, and Helicobacter pylori (H. pylori)infection was detected in normal controls using serologic methods. PCR-RFLP method was used to detect the genotype distribution of the GPX4 rs2074452. Unconditional Logistic regression was used to calculate its genotype and allele frequency and analyze its association with H. pylori infection and the risk of non-cardia gastric cancer. Results: rs2074452 was not related with the risk of H. pylori infection, but it was associated with the risk of non-cardia gastric cancer. In the recessive model, the TT genotype reduced the risk of non-cardia gastric cancer compared with the CC+CT genotype (OR=0.214, 95% CI: 0.061-0.756). Conclusion: The TT genotype of GPX4 rs2074452 may be a protective factor for the development of non-cardia gastric cancer.
[1] Han BF, Zheng RS, Zeng HM, et al. Cancer incidence and mortality in China, 2022[J/OL]. J National Cancer Center, 2024, 4(1): 47-53.
[2] Yang L, Kartsonaki C, Yao P, et al. The relative and attributable risks of cardia and non-cardia gastric cancer associated with helicobacter pylori infection in china: a case-cohort study[J]. Lancet Public Health, 2021, 6(12): e888-e896.
[3] Shirani M, Pakzad R, Haddadi MH, et al. The global prevalence of gastric cancer in Helicobacter pylori-infected individuals:a systematic review and meta-analysis[J]. BMC Infect Dis, 2023, 23(1): 543.
[4] Peek RM Jr, Crabtree JE. Helicobacter infection and gastric neoplasia[J]. J Pathol, 2006, 208(2): 233-248.
[5] 阎小霞, 张云翔, 高芳, 等. TEAD2 rs3745305与非贲门胃癌变关系的研究[J]. 包头医学院学报, 2022, 38(3): 10-14.
[6] 刘得利. DNMT1与非贲门胃癌的关系研究[D]. 包头: 内蒙古科技大学包头医学院, 2021.
[7] Zhang SZ, Zhang L, Xie L. Cancer burden in China during 1990-2019:analysis of the global burden of disease[J]. Biomed Res Int, 2022, 2022: 3918045.
[8] Areia M, Spaander MC, Kuipers EJ, et al. Endoscopic screening for gastric cancer: a cost-utility analysis for countries with an intermediate gastric cancer risk[J]. United European Gastroenterol J, 2018, 6(2): 192-202.
[9] Xu WT, Xu LM, Xu CF. Relationship between helicobacter pylori infection and gastrointestinal microecology[J]. Front Cell Infect Microbiol, 2022, 12: 938608.
[10] Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease[J]. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
[11] Guerriero E, Capone F, Accardo M, et al. GPX4 and GPX7 over-expression in human hepatocellular carcinoma tissues[J]. Eur J Histochem, 2015, 59(4): 2540.
[12] Yagublu V, Arthur JR, Babayeva SN, et al. Expression of selenium-containing proteins in human colon carcinoma tissue[J]. Anticancer Res, 2011, 31(9): 2693 -2698.
[13] 张波, 霍明东, 马俊, 等. 谷胱甘肽过氧化物酶4对结直肠癌细胞系SW480瑞格菲尼抵抗的影响及机制研究[J]. 中国临床药理学杂志, 2020, 36(6): 647-650, 654.
[14] Peng GQ, Tang ZW, Xiang YJ, et al. Glutathione peroxidase 4 maintains a stemness phenotype, oxidative homeostasis and regulates biological processes in Panc-1 cancer stem-like cells[J]. Oncol Rep, 2019, 41(2): 1264-1274.
[15] Sugezawa K, Morimoto M, Yamamoto M, et al. GPX4 regulates tumor cell proliferation via suppressing ferroptosis and exhibits prognostic significance in gastric cancer[J]. Anticancer Res, 2022, 42(12): 5719-5729.
[16] Wang Y, Zheng LX, Shang WJ, et al. Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer[J]. Cell Death Differ, 2022, 29(11): 2190-2202.
[17] Jian H, Chen ZQ, Du H, et al. Inhibition of ferroptosis by POLE2 in gastric cancer cells involves the activation of NRF2/GPX4 pathway[J]. J Cell Mol Med, 2024, 28(1): e17983.
[18] Wang TA, Zhou ZH, Wang CM, et al. LTBP2 knockdown promotes ferroptosis in gastric cancer cells through p62-Keap1-Nrf2 pathway[J]. Biomed Res Int, 2022, 2022: 6532253.
[19] Ye SP, Lin R, Guo X, et al. Bioinformatics analysis on the expression of GPX family in gastric cancer and its correlation with the prognosis of gastric cancer[J]. Heliyon, 2022, 8(12): e12214.
[20] Hu C, Zu D, Xu Jl, et al. Polyphyllin B suppresses gastric tumor growth by modulating iron metabolism and inducing ferroptosis[J]. Int J Biol Sci, 2023, 19(4): 1063-1079.
[21] Zhao LY, Peng YM, He SX, et al. Apatinib induced ferroptosis by lipid peroxidation in gastric cancer[J]. Gastric Cancer, 2021, 24(3): 642-654.
[22] Geybels MS, Hutter CM, Kwon EM, et al. Variation in selenoenzyme genes and prostate cancer risk and survival[J]. Prostate, 2013, 73(7): 734-742.
[23] Peters U, Chatterjee N, Hayes RB, et al. Variation in the selenoenzyme genes and risk of advanced distal colorectal adenoma[J]. Cancer Epidemiol Biomarkers Prev, 2008, 17(5): 1144-1154.
