Genetic mutation rs972283 of the KLF14 gene and the incidence of gastric cancer
Keywords:Gastric Cancer, single nucleotide polymorphism, rs972283, KLF14 gene, Tetra Primer, ARMS-PCR
Introduction and Aim: Genetic factors and family gene clustering constitute an important ratio for gastric cancer. Kruppel Like Factor 14 (KLF14) gene has a carcinogenic role and a clear role in metabolic diseases, but how this gene regulates these metabolic traits is still obscure. Previous studies proposed that the accumulation of single nucleotide polymorphisms (SNPs) in KLF14 may be associated with gastric cancer. The current study aimed to investigate whether single nucleotide polymorphisms (SNP) rs972283 in KLF14 is associated with an increased risk of gastric cancer in the Iraqi population.
Materials and Methods: The SNP was genotyped using tetra primer ARMS-PCR in 101 (79 men and 22 women) gastric cancer patients who did not receive chemotherapy, and 80 healthy controls (53 men and 27 women). All patient samples were taken from the Baghdad Hospital of Gastroenterology and Hepatology laboratories. Patient records included age, sex, histological type, and H. pylori infection status
Results: The KLF14 rs972283 genotype was significantly different between the gastric cancer and control groups. The heterozygous AG genotype and A mutant allele were significantly higher in gastric cancer patients compared to controls (56.4% vs 38.7%, p<0.01 and 61% vs 40.6%, p<0.01, respectively). In contrast, the GG wildtype genotype and G wildtype allele were significantly higher in controls (40% vs 11%, p<0.01 and 59.4% vs 39%, p<0.01, respectively). The AA homozygous mutant genotype also showed a weak correlation with increased gastric cancer risk. These results indicate the A allele is a risk factor while the G allele has a protective effect for gastric cancer.
Conclusion: the KLF14 polymorphism rs972283 exhibits a significant association with gastric cancer risk in our Iraqi cohort. The SNP may serve as a useful prognostic marker, pending validation in larger studies.
Lobo, L., Rohith, M. J., Kishan Prasad, H. L. Utility of serum interleukin-18 (IL-18) as a tumour marker in gastric cancer. Biomedicine. 2022 Nov 14;42(5):1079-1082.
Rawla, P., Barsouk, A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019; 14(1):26-38.
Menon, D., Sekhar, G. PD-L1 expression in gastric carcinoma–a biomarker for immunotherapy. Biomedicine. 2022 May 1;42(2):383-387.
Bodepudi, S., Muralitharan, S., Gunabooshanam, B. A study of immunohistochemical expression of PD-L1 in gastric carcinoma. Biomedicine. 2021 Oct 29;41(3):630-637.
Machlowska, J., Baj, J., Sitarz, M., Maciejewski, R., Sitarz, R. Gastric cancer: Epidemiology, Risk factors, classification, genomic characteristics and treatment strategies. International Journal of Molecular Sciences. 2020; 21(11):4012.
Al-Deresawi,M.S., Bresam, B., AL-Faisal, A. H. M. Compound FGFR3 mutations associated with grads of bladder carcinoma. Res J Pharm. Biol. Chem. Scie. 2019; 10(2):1464-1469.
Mustafa, A.J. and Ismail, P.A. Association of potent inflammatory cytokine and oxidative dna damage biomarkers in stomach cancer patients. Baghdad Science Journal. 2022; 19(6): 1313-1325.
Luo, X.H., Liu, J.Z., Wang, B., Men, Q.L., Ju, Y.Q., Yin, F.Y., et al., KLF14 potentiates oxidative adaptation via modulating HO-1 signaling in castrate-resistant prostate cancer. Endocr Relat Cancer. 2019; 26: 181-195.
Koppes, E., Shaffer, B., Sadovsky, E., Himes, K., Barak, Y., Sadovsky, Y. et al., Klf14 is an imprinted transcription factor that regulates placental growth. Placenta. 2019; 88: 61-67.
Stacey, S.N., Sulem, P., Masson, G., Gudjonsson, S.A., Thorleifsson, G., Jakobsdottir, M. et al., New common variants affecting susceptibility to basal cell carcinoma. Nat Genet. 2009; 41: 909-914.
Zabala, A.S., Gomez, M.E.V., Álvarez, M.F., Siewert, S. Tetra Primer ARMS PCR Optimization to detect single nucleotide polymorphism of the KLF14 gene. Open Access Libr. 2017; 4: e4145.
SAS. Statistical Analysis System, User's Guide. Statistical. Version 9.1th ed. SAS. Inst. Inc. Cary. N.C. USA. 2012.
Hachim, S. K., Ali, A. S. The role of Helicobacter pylori in gastric cancer: A review. Biomedicine. 2020 Nov 9;40(3):267-271.
Li, Z., Yao, H., Wang, S., Li, G., Gu, X. CircTADA2A suppresses the progression of colorectal cancer via miR-374a-3p/KLF14 axis. Journal of Experimental and Clinical Cancer Research. 2020; 39(1): 1-14.
Jabar, S.A., ALFaisal, A.H.M. The correlation between KRAS mutations and H. pylori in gastric cancer patients. Iraqi Journal Bio. 2017; 16 (3): 82-93.
Sato, N., Ito, Y., Ioka, A., Tanaka, M.,Tsukuma, H. Gender differences in stomach cancer survival in Osaka, Japan: Analyses using relative survival model. Jpn J Clin Oncol. 2009; 10: 690-694.
Mwafaq, R.K., Abbas, A.K., Abdullah, L.A.H., Ghafour, K.H.A. The immunohistochemically estimation of CD63 in Iraqi patients with gastric cancer. Baghdad Science Journal. 2022; 19: 932-349.
Martínez-Galindo, M.G., Zamarripa-Dorsey, F., Carmona-Castañeda, A., Angeles-Labra, A., Peñavera-Hernández, R., Ugarte-Briones, C. et al., Histopathologic characteristics of gastric adenocarcinoma in Mexican patients: A 10-year experience at the hospital Juárez de México. Revista de Gastroenterología de México.2015; 80: 21-26.
Tang, X., Zhang, M., He, Q., Sun, G., Wang, C., Gao, P. et al., Histological differentiated/undifferentiated mixed type should not be considered as a non-curative factor of endoscopic resection for patients with early gastric cancer. Front. Oncol. 2020; 10(3): 1743.
Su, M. K., Byung-Hoon, M., Lee, J., Yeong, J., Jun H. L., Sung, T., et al., Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type Gastric Adenocarcinoma. Yonsei Med J. 2018; 59: 28–34.
Kalff, M.C., Wagner, A.D., Verhoeven, R.H., Lemmens, V.E., van Laarhoven, H.W., Gisbertz, S.S. et al., Sex differences in tumor characteristics, treatment, and outcomes of gastric and esophageal cancer surgery: nationwide cohort data from the Dutch Upper GI Cancer Audit. Gastric Cancer. 2022; 25(1): 22-32.
Kim, S.M., Min, B.H., Lee, J., An, J.Y., Lee, J.H., Sohn, T.S. et al., Protective effects of female reproductive factors on Lauren intestinal-type gastric adenocarcinoma. Yonsei Med J.2018; 59(1):28-34.
Ma, Z., Liu, X., Paul, M.E., Chen, M., Zheng, P.Chen, H. Comparative investigation of early onset gastric cancer (Review). ONC. Letters. 2021; 21:374-370.
AL-Faisal, A.H.M.,Bresam, S. Association of Exon 9 FGFR3 mutations and cancer grads in patients with bladder cancer. Iraqi Journal of Biotechnology. 2016; 15(2): 109-118.
Bresam, S., Rakad, M., Gulbahar F., Al-Rubaii. B. Polymorphism in SNP rs972283 of the KLF14 gene and genetic disposition to peptic ulcer. Biomedicine. 2023; 43: 216-220.
Yang, Q., Civelek, M. Transcription Factor KLF14 and metabolic syndrome. Int J Mol Sci. 2020; 8: 4165-4178.
Kilgour, J.M., Jia, J.L., Sarin, K.Y. Review of the molecular genetics of basal cell carcinoma; Inherited susceptibility, somatic mutations, and targeted therapeutics. Cancers (Basel). 2021;13:3870-3886.
Mokhtarian, R., Tabatabaeian, H., Saadatmand, P., Azadeh, M., Balmeh, N., Yakhchali, B. et al., CD44 gene rs8193 C allele is significantly enriched in gastric cancer patients. Cell J. 2020; 21(4):451-458.
Chen, X., Shi, W., Zhang, H. The role of KLF14 in multiple disease processes. Biofactors. 2020; 46:276-282.
How to Cite
Copyright (c) 2023 Biomedicine
This work is licensed under a Creative Commons Attribution 4.0 International License.