title: Association of TNF-α, TNFRSF1A and TNFRSF1B gene polymorphisms with the risk of sporadic breast cancer in northeast Chinese Han women.
abstract: BACKGROUND
  The interaction of tumor necrosis factor-α (TNF-α) with its receptors: TNFRSF1A and TNFRSF1B is critical for the promotion of tumor growth, invasion and metastasis. To better understand the roles of single nucleotide polymorphisms (SNPs) in the TNF-α, TNFRSF1A and TNFRSF1B genes in the development of breast cancer, we explored the associations between SNPs in these three genes and breast cancer susceptibility in northeast Chinese Han women.
  
  
  RESULTS
  This case-control study was conducted among 1016 breast cancer patients and 806 age-matched healthy controls. Seven SNPs in the TNF-α (rs1800629, rs361525), TNFRSF1A (rs767455, rs4149577 and rs1800693) and TNFRSF1B (rs1061622 and rs1061624) genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In TNFRSF1B, the rs1061622 GT genotype and the G allele conferred a reduced susceptibility to breast cancer (P = 0.000662, OR = 0.706, 95% CI: 0.578-0.863; P = 0.002, OR = 0.769, 95% CI; 0.654-0.905, respectively). Moreover, the AG genotype, the AA genotype and the A allele in rs1061624 conferred an increased risk of breast cancer (P = 0.007, OR = 1.470, 95% CI:1.112-1.943; P = 0.00109, OR = 1.405 95% CI:1.145-1.724; P = 0.001, OR = 1.248 95% CI:1.092-1.426, respectively). These two SNPs also had associations with breast cancer risk under the dominant model. In haplotype analysis, the CTA (rs767455 C-rs4149577 T-rs1800693 A) haplotype in TNFRSF1A and the TA (rs1061622 T-rs1061624 A) haplotype in TNFRSF1B had higher frequencies in breast cancer patients (P = 0.00324; P = 0.000370, respectively), but the frequency of GG (rs1061622 G-rs1061624 G) haplotype in TNFRSF1B was lower in breast cancer patients (P = 0.000251). The associations of the three haplotypes remained significant after correcting for multiple testing. In addition, significant associations were also observed between TNFRSF1A polymorphisms and lymph node metastasis, P53, estrogen receptor (ER) and progesterone receptor (PR) statuses.
  
  
  CONCLUSIONS
  Our results suggest that rs1061622 and rs1061624 in TNFRSF1B may affect breast cancer risk, and SNPs in TNFRSF1A are associated with the clinical features of breast cancer.
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: Guiqin
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Han
authors.affiliation: Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Surgery, the Third Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Heilongjiang Provincial Key Laboratory for Infection and Immunity, Harbin Medical University, Harbin, China; Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin, China.
authors.forename: Dianjun
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Surgery, the Third Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Da
authors.initials: D
authors.lastname: Pang
mesh_terms: D044466:Asian People / Q000208:ethnology* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506235:TNFRSF1A protein, human; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha