A polymorphic 9-bp deletion in exon 1 of TGFBR1 (TGFBR1*6A) has been identified as a low-penetrance cancer susceptibility allele. The strongest association in the initial studies was with breast cancer; however, these studies included patients with different types of cancer, including colon, cervical and breast carcinomas, with only a small proportion being breast cancer patients. In subsequent case–control studies focussing on breast cancer alone, the results have been equivocal. In order to clarify whether TGFBR1*6A is associated with breast cancer risk, we have genotyped this polymorphism in 988 breast cancer cases and 1,016 controls from the West of Ireland and also performed a meta-analysis of previously published data (5,150 cases and 6,344 controls). In our series from the West of Ireland, we found no association (genotypic odds ratio (OR) under a dominant model = 0.93, 95% confidence interval (CI) 0.73–1.19, P = 0.57; allelic OR = 0.93, 95% CI 0.74–1.15, P = 0.49). Meta-analysis showed evidence of heterogeneity among studies. Using the random effects model, it was found that there was no evidence of an association of the *6A allele with breast cancer (genotypic OR under a dominant model = 1.10, 95% CI = 0.94–1.28, P = 0.24, allelic OR = 1.12, 95% CI 0.97–1.31, P = 0.13). In conclusion, our study shows that there is no association between TGFBR1*6A and breast cancer risk.
Breast cancerGenetic susceptibilityTGFBR1West IrelandMeta-analysis