The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer
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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.
KeywordsBreast cancer Genetic susceptibility TGFBR1 West Ireland Meta-analysis
We are grateful to the patients in the study and colleagues involved in patient ascertainment and sample collection. Help was also kindly provided by the Equipment Park, London Research Institute, Cancer Research UK. NM and GC were funded by the National Breast Cancer Research Institute, Ireland. ES and AJ were funded by the Department of Health Clinician Scientist Grant, UK.
- 2.Chen T, de Vries EG, Hollema H et al (1999) Structural alterations of transforming growth factor-beta receptor genes in human cervical carcinoma. Int J Cancer 82:43–51. doi: 10.1002/(SICI)1097-0215(19990702)82:1<43::AID-IJC9>3.0.CO;2-0 PubMedCrossRefGoogle Scholar
- 10.McInerney N, Colleran G, Rowan A, et al. (2008) Low penetrance breast cancer predisposition SNPs are site specific. Breast Cancer Res Treat (Nov):13. Epub ahead of print. PMID: 19005751Google Scholar
- 11.Feigelson HS, Patel AV, Diver WR et al (2006) Transforming growth factor beta receptor type I and transforming growth factor beta1 polymorphisms are not associated with postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 15(6):1236–1237. doi: 10.1158/1055-9965.EPI-06-0163 PubMedCrossRefGoogle Scholar