title: A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression.
abstract: Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2.004 (95% confidence internal [CI] = 1.190-3.375). Multivariate Cox regression analysis in 309 of 417 cases showed that rs1259293 genotype (CC vs TT + CT) independently predicted an unfavorable prognosis, with a hazard ratio of 2.531 (95% CI = 1.052-6.086). Expression of FSTL1 was significantly higher in adjacent renal tissues than in tumors, and significantly higher in the tissues with rs1259293 TT genotype than in those with rs1259293 TC+CC genotypes. rs1259293 C allele might generate a CTCF binding site that blocks trans-activation of FSTL1 expression. Our results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of RCC, possibly by down-regulating FSTL1 expression in renal tissues.
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chronic Diseases, Center for Diseases Control and Prevention of Yangpu District, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pathology, the 1st affiliated hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Zixiong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Urology, the 1st affiliated hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Chronic Diseases, Center for Diseases Control and Prevention of Yangpu District, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Genitourinary Medical Oncology-Research, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Thompson
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Epidemiology, Second Military Medical University, Shanghai, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D038702:Follistatin-Related Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D038702:Follistatin-Related Proteins; D009363:Neoplasm Proteins; C448799:FSTL1 protein, human