Association between apolipoprotein E polymorphisms and gastric cancer in a hospital-based Turkish population

Abstract

Apolipoprotein E (ApoE) is an important secretory glycoprotein, and also a ligand for LDL receptors and ApoE receptors. It is involved in lipid transport and catabolism, nerve regeneration, immune system regulation, and cell proliferation. Moreover, both the causative and protective effects of APOE polymorphic variants and alleles have been correlated with several diseases, including cancer types such as gastric cancer. However, to the best of our knowledge, no data are available describing the association between gastric cancer and APOE polymorphisms in the Turkish population. In this context, this study was conducted to evaluate the association between the genotypes of APOE and the risk of gastric cancer and also to demonstrate the allele frequencies and genotype distributions of APOE gene in a hospital-based Turkish population with gastric cancer. A total of 59 patients with gastric cancer and 200 healthy controls were included in this study. Results showed the absence of any statistically significant association between APOE gene polymorphisms and the risk of gastric cancer (χ2 =2.711, p=0.744), which could possibly be due to the small sample size of our study. Therefore, further investigations such as expression studies and meta-analysis comprising larger sample size and detailed demographic data are necessary to identify the alleles of APOE gene associated with the risk of gastric cancer. 

Keywords

• Gastric Cancer,ApoE polymorphisms,Turkish population

References

1. Acar Çinleti B, Yardimci N, Aytürk Z, Ilhan A, Kaya G, Acar M, Koç ER, Gündüz E, Gündüz M (2015). The effects and interactions of APOE and APH-1A polymorphisms in Alzheimer disease. Turk J Med Sci. 45(5):1098-105.
2. Alaylıoğlu M, Gezen-Ak D, Dursun E, Bilgiç B, Hanağası H, Ertan T, Gürvit H, Emre M, Eker E, Uysal Ö, Yılmazer S (2016). The Association Between Clusterin and APOE Polymorphisms and Late-Onset Alzheimer Disease in a Turkish Cohort. J Geriatr Psychiatry Neurol. 29(4):221-6.
3. Cetinkalp S, Karadeniz M, Erdogan M, Zengi A, Cetintas V, Tetik A, Eroglu Z, Kosova B, Ozgen AG, Saygili F, Yilmaz C (2009). Apolipoprotein E gene polymorphism and polycystic ovary syndrome patients in Western Anatolia, Turkey. J Assist Reprod Genet. 26(1):1-6.
4. Cibeira GH, Giacomazzi J, Aguiar E, Schneider S, Ettrich B, DE Souza CI, Camey S, Caleffi M, Weber B, Ashton-Prolla P, Moriguchi EH (2014). Apolipoprotein E genetic polymorphism, serum lipoprotein levels and breast cancer risk: A case-control study. Mol Clin Oncol. 2(6):1009-1015.
5. De Feo E, Simone B, Persiani R, Cananzi F, Biondi A, Arzani D, Amore R, D’Ugo D, Ricciardi G, Boccia S (2012). A case–control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression. BMC Cancer 12, 494.
6. Erdogan M, Eroglu Z, Kulaksizoglu M, Soner S, Tetik A, Cetinkalp S (2016). The relationship of the apolipoprotein E gene polymorphism in Turkish Type 2 Diabetic Patients with and without diabetic foot ulcers. Diabetes Metab Syndr. 10(1 Suppl 1):S30-3.
7. Kang R, Li P, Wang T, Li X, Wei Z, Zhang Z, Zhong L, Cao L, Heckman MG, Zhang YW, Xu H, Huang C, Bu G, Chen XF (2016). Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population. Sci Rep. 28;6:19930.
8. Liu YL, Zhang HM, Pan HM, Bao YH, Xue J, Wang TC, Dong XC, Li XL, Bao HG (2016). The relationship between apolipoprotein E gene ε2/ε3/ε4 polymorphism and breast cancer risk: a systematic review and meta-analysis. Onco Targets Ther. 9:1241-9.

9. Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extractingDNA from human nucleated cells. Nucleic Acids Res. 16(3): 1215.
10. Ni J, Shen N, Tang J, Ren K (2017). Correlation between protein kinase catalytic subunit alpha-1 gene rs13361707 polymorphism and gastric cancer susceptibility in asian populations. Oncotarget 8(40):68354-68364.
11. Niemi M, Kervinen K, Kiviniemi H, Lukkarinen O, Kyllo¨nen A-P, Sarkkinen MA, Savolainen MJ, KairaluomaMI, Kesaniemi YA (2000). Apolipoprotein E phenotype, cholesterol and breast and prostate cancer. J Epidemiol Commun Health 54:938–9.
12. Parkin DM, Bray FI, Devesa SS (2001). Cancer burden in the year 2000. The global picture. Eur J Cancer. Suppl 8:S4-66.
13. Sakashita K, Tanaka F, Zhang X, Mimori K, Kamohara Y, Inoue H, Sawada T, Hirakawa K, Mori M (2008). Clinical significance of ApoE expression in human gastric cancer. Oncol Rep. 20(6):1313-9.
14. Sazci A, Akpinar G, Aygun C, Ergul E, Senturk O, Hulagu S (2008). Association ofapolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis. Dig Dis Sci. 53(12):3218-24.
15. Shi X, Xu J, Wang J, Cui M, Gao Y, Niu H, Jin H (2015). Expression analysis of apolipoprotein E and its associated genes in gastric cancer. Oncology Letters 10(3), 1309–1314.
16. Sipponen P (2002). Gastric cancer: pathogenesis, risks, and prevention. J Gastroenterol Suppl 13:39-44.
17. Sun H, Wu X, Wu F, Li Y, Yu Z, Chen X, Chen Y, Yang W (2015). Associations of Genetic Variants in the PSCA, MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population. PLoS ONE 10(2), e0117576.
18. Tasdemir N, Tamam Y, Toprak R, Tamam B, Tasdemir MS (2008). Association of apolipoprotein E genotype and cerebrovascular disease risk factors in a Turkish population. Int J Neurosci. 118(8):1109-29.
19. Uen YH, Liao CC, Lin JC, Pan YH, Liu YC, Chen YC, Chen WJ, Tai CC, Lee KW, Liu YR, Lin HT, Lin CY (2015). Analysis of differentially expressed novel post-translational modifications of plasma apolipoprotein E in Taiwanese females with breast cancer. J Proteomics 3;126:252-62.
20. Weisgraber KH (1990). Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112. J Lipid Res. 31(8):1503-11.
21. Yaghoobi M, Bijarchi R, Narod SA (2010). Family history and the risk of gastric cancer. BrJ Cancer 102(2):237-242.
22. Yaylim İ, Bozkurt N, Yilmaz H, Isbir T, Isik N, Arikan S (2003).The apolipoprotein E ε4 allele is not a risk factor for Turkish breast cancer patients. Cancer Genetics and Cytogenetics. 146: 86–87.
23. Yencilek F, Yilmaz SG, Yildirim A, Gormus U, Altinkilic EM, Dalan AB, Bastug Y, Turkmen S, Turkan S, Isbir T (2016). Apolipoprotein E Genotypes in Patients with Prostate Cancer. Anticancer Res. 36(2):707-11.
24. Yılmaz-Aydogan H, Kucukhuseyin O, Kurnaz O, Akadam-Teker B, Kurt O, Tekeli A, Ozturk O, Isbir T (2012). Investigation of polymorphic variants of PPARD and APOE genes in Turkish coronary heart disease patients. DNA Cell Biol. 31(5):867-75.
25. Zannis VI, Breslow JL, Utermann G, Mahley RW, Weisgraber KH, Havel RJ, Goldstein JL, Brown MS, Schonfeld G, Hazzard WR, Blum C (1982). Proposed nomenclature of apoE isoproteins, apoE genotypes, and phenotypes. J Lipid Res. 23(6):911-4.
26. (2017)Cancer Statistics Center. Stomach, https://cancerstatisticscenter.cancer.org/#!/cancer-site/Stomach. Accessed 18.10.2017.
27. (2017)Canser Research UK. Stomach cancer incidance statistics, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer type/stomach-cancer/incidence#heading-Zero. Accessed 18.10.2017.
28. (2017)Türkiye Halk Sağlığı Kurumu, Kanser Daire Başkanlığı. Mide Kanseri, http://kanser.gov.tr/kanser/kanser-turleri/223-mide-kanseri.html. Accessed 18.10.2017.
29. (2017)Uniprot. UniProtKB - P02649 (APOE_HUMAN), http://www.uniprot.org/uniprot/P02649. Accessed 18.10.2017.