Polymorphisms of the FAS and FASL genes and risk of breast cancer

Wang,Wenmin; Zheng,Zhongqiu; Yu,Wenjie; Lin,Hui; Cui,Binbin; Cao,Feilin

doi:10.3892/ol.2011.541

Polymorphisms of the FAS and FASL genes and risk of breast cancer

Authors:
- Wenmin Wang
- Zhongqiu Zheng
- Wenjie Yu
- Hui Lin
- Binbin Cui
- Feilin Cao
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Affiliations: Department of Surgical Oncology, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000, P.R. China
Published online on: December 28, 2011 https://doi.org/10.3892/ol.2011.541
Pages: 625-628

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Abstract

FAS and its ligand FASL are crucial in apoptotic cell death. Loss of FAS and gain of aberrant FASL expression are common features of malignant transformation. This study was designed to investigate whether the functional polymorphisms of FAS -1377G/A (rs2234767) and FASL -844T/C (rs763110) affect the risk of developing breast cancer. Genotypes were analyzed by a polymerase chain reaction‑restriction fragment length polymorphism assay in 436 breast cancer patients and 496 healthy controls. In this study, as compared to the wild-type homozygote and heterozygote, the distribution of the FAS -1377GG, GA and AA genotypes among breast cancer patients were significantly different from those among healthy controls (P=0.011), with the AA genotype being more prevalent among patients than the controls (P=0.003). Similarly, the frequencies of the FASL -844TT, TC and CC genotypes also significantly differed among breast cancer patients and healthy controls (P<0.001), with the CC genotype being significantly over-represented in breast cancer patients compared with the controls (P<0.001). In the unconditional logistic regression model following adjustment for age, the subjects carrying the FAS -1377AA genotype had a 1.75-fold increased risk [95% confidence interval (CI), 1.13-2.69] for development of breast cancer compared with patients carrying the GG genotype. Similarly, in the recessive model, the FASL -844CC genotype significantly increased the risk of breast cancer with an odds ratio (OR) of 1.92 (95% CI 1.46-2.54) compared with the TT or TT + TC genotypes. Our results suggest that functional polymorphisms in the death pathway genes FAS and FASL significantly contribute to the occurrence of breast cancer.

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1	Fan XQ and Guo YJ: Apoptosis in oncology. Cell Res. 11:1–7. 2001. View Article : Google Scholar
2	Evan GI and Vousden KH: Proliferation, cell cycle and apoptosis in cancer. Nature. 411:342–348. 2001. View Article : Google Scholar : PubMed/NCBI
3	Andera L: Signaling activated by the death receptors of the TNFR family. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 153:173–180. 2009. View Article : Google Scholar : PubMed/NCBI
4	Kim R, Emi M, Tanabe K, Uchida Y and Toge T: The role of Fas ligand and transforming growth factor β in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy. Cancer. 100:2281–2291. 2004.
5	Reichmann E: The biological role of the Fas/FasL system during tumor formation and progression. Semin Cancer Biol. 12:309–315. 2002. View Article : Google Scholar : PubMed/NCBI
6	Randhawa SR, Chahine BG, Lowery-Nordberg M, Cotelingam JD and Casillas AM: Underexpression and overexpression of Fas and Fas ligand: a double-edged sword. Ann Allergy Asthma Immunol. 104:286–292. 2010. View Article : Google Scholar : PubMed/NCBI
7	Whiteside TL: The role of death receptor ligands in shaping tumor microenvironment. Immunol Invest. 36:25–46. 2007. View Article : Google Scholar : PubMed/NCBI
8	Fulda S and Pervaiz S: Apoptosis signaling in cancer stem cells. Int J Biochem Cell Biol. 42:31–38. 2010. View Article : Google Scholar : PubMed/NCBI
9	Houston A and O'Connell J: The Fas signalling pathway and its role in the pathogenesis of cancer. Curr Opin Pharmacol. 4:321–326. 2004. View Article : Google Scholar : PubMed/NCBI
10	Wajant H: The Fas signaling pathway: more than a paradigm. Science. 296:1635–1636. 2002. View Article : Google Scholar : PubMed/NCBI
11	Huang QR, Morris D and Manolios N: Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. Mol Immunol. 34:577–582. 1997. View Article : Google Scholar : PubMed/NCBI
12	Wu J, Metz C, Xu X, Abe R, Gibson AW, Edberg JC, Cooke J, Xie F, Cooper GS and Kimberly RP: A novel polymorphic CAAT/enhancer-binding protein β element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. J Immunol. 170:132–138. 2003.PubMed/NCBI
13	Zhang Z, Qiu L, Wang M, Tong N, Li J and Zhang Z: The FAS ligand promoter polymorphism, rs763110 (-844C>T), contributes to cancer susceptibility: evidence from 19 case-control studies. Eur J Hum Genet. 17:1294–1303. 2009.
14	Zhang Z, Xue H, Gong W, Wang M, Yuan L, Han S and Zhang Z: FAS promoter polymorphisms and cancer risk: a meta-analysis based on 34 case-control studies. Carcinogenesis. 30:487–493. 2009. View Article : Google Scholar : PubMed/NCBI
15	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
16	Keane MM, Ettenberg SA, Lowrey GA, Russell EK and Lipkowitz S: Fas expression and function in normal and malignant breast cell lines. Cancer Res. 56:4791–4798. 1996.PubMed/NCBI
17	Herrnring C, Reimer T, Jeschke U, Makovitzky J, Krüger K, Gerber B, Kabelitz D and Friese K: Expression of the apoptosis-inducing ligands FasL and TRAIL in malignant and benign human breast tumors. Histochem Cell Biol. 113:189–194. 2000. View Article : Google Scholar : PubMed/NCBI
18	Müllauer L, Mosberger I, Grusch M, Rudas M and Chott A: Fas ligand is expressed in normal breast epithelial cells and is frequently up-regulated in breast cancer. J Pathol. 190:20–30. 2000.PubMed/NCBI
19	Sun T, Miao X, Zhang X, Tan W, Xiong P and Lin D: Polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma. J Natl Cancer Inst. 96:1030–1036. 2004. View Article : Google Scholar : PubMed/NCBI
20	Zhang X, Miao X, Sun T, Tan W, Qu S, Xiong P, Zhou Y and Lin D: Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer. J Med Genet. 42:479–484. 2005. View Article : Google Scholar : PubMed/NCBI
21	Lai HC, Sytwu HK, Sun CA, Yu MH, Yu CP, Liu HS, Chang CC and Chu TY: Single nucleotide polymorphism at Fas promoter is associated with cervical carcinogenesis. Int J Cancer. 103:221–225. 2003. View Article : Google Scholar : PubMed/NCBI
22	Liu Y, Wen QJ, Yin Y, Lu XT, Pu SH, Tian HP, Lou YF, Tang YN, Jiang X, Lu GS and Zhang J: FASLG polymorphism is associated with cancer risk. Eur J Cancer. 45:2574–2578. 2009. View Article : Google Scholar : PubMed/NCBI
23	Wang LH, Ting SC, Chen CH, Tsai CC, Lung O, Liu TC, Lee CW, Wang YY, Tsai CL and Lin YC: Polymorphisms in the apoptosis-associated genes FAS and FASL and risk of oral cancer and malignant potential of oral premalignant lesions in a Taiwanese population. J Oral Pathol Med. 39:155–161. 2010. View Article : Google Scholar : PubMed/NCBI
24	Kang S, Dong SM, Seo SS, Kim JW and Park SY: FAS -1377 G/A polymorphism and the risk of lymph node metastasis in cervical cancer. Cancer Genet Cytogenet. 180:1–5. 2008. View Article : Google Scholar : PubMed/NCBI
25	Qiu LX, Shi J, Yuan H, Jiang X, Xue K, Pan HF, Li J and Zheng MH: FAS -1,377 G/A polymorphism is associated with cancer susceptibility: evidence from 10,564 cases and 12,075 controls. Hum Genet. 125:431–435. 2009. View Article : Google Scholar : PubMed/NCBI
26	Shimonishi T, Isse K, Shibata F, Aburatani I, Tsuneyama K, Sabit H, Harada K, Miyazaki K and Nakanuma Y: Up-regulation of fas ligand at early stages and down-regulation of Fas at progressed stages of intrahepatic cholangiocarcinoma reflect evasion from immune surveillance. Hepatology. 32:761–769. 2000. View Article : Google Scholar : PubMed/NCBI
27	Yang M, Sun T, Wang L, Yu D, Zhang X, Miao X, Liu J, Zhao D, Li H, Tan W and Lin D: Functional variants in cell death pathway genes and risk of pancreatic cancer. Clin Cancer Res. 14:3230–3236. 2008. View Article : Google Scholar : PubMed/NCBI
28	Zhu J, Qin C, Wang M, Yan F, Ju X, Meng X, Ding Q, Li P, Yang J, Cao Q, Zhang Z and Yin C: Functional polymorphisms in cell death pathway genes and risk of renal cell carcinoma. Mol Carcinog. 49:810–817. 2010.PubMed/NCBI