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.
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