The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer.

A polymorphic 9-bp deletion in exon 1 of TGFBR1 (TGFBR16A) 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 TGFBR16A 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 TGFBR16A and breast cancer risk.