title: Polymorphisms of tumour necrosis factors A and B in breast cancer.
abstract: We assayed for germline single nucleotide polymorphisms (SNPs) in the TNFB and TNFA genes in patients with breast cancer. SNPs were observed in the first intron of TNFB (G/A) and at -1031 (T/C), -863 (C/A), -857 (C/T) and -308 (G/A) in the promoter region of TNFA from peripheral leucocytes in 95 breast cancer patients and 190 healthy subjects as controls. The TNFB*G/TNFB*G homozygote (23.2% vs. 5.8%, P= 0.001) was predominant in patients, while the TNFB*A/TNFB*A homozygote was less frequent in patients (34.7% vs. 46.3%, P = 0.041) than in the control subjects. Breast cancer was not associated with SNPs in the TNFA promoters. Although the TNFB SNP failed to associate with any clinicopathological parameter of breast cancer, a substantial difference in pathology among tumour stages for the -857 SNP in TNFA was detected. These results indicate that TNFB has both tumorigenic and antitumorigenic capabilities depending on the genotype: the TNFB SNP TNFB*G/TNFB*G genotype gave an increased risk for breast cancer and that of TNFB*A/TNFB*A gave resistance to breast cancer (OR = 5.3395%; CI: 2.33-12.19). The results suggest that the TNFB*G allele plays some role in the tumorigenesis or activation of dormant tumour cells, but the TNFB*A allele induces some function(s) leading to the inhibition of tumorigenesis.
authors.affiliation: Department of Biology, Sungshin Women's University, 249-1 Dongsun-dong, Sungbuk-ku, Seoul 136-742, Korea. kspark@cc.sungshin.ac.kr
authors.forename: K S
authors.initials: KS
authors.lastname: Park
authors.forename: J W
authors.initials: JW
authors.lastname: Mok
authors.forename: H E
authors.initials: HE
authors.lastname: Ko
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha