title: The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer.
abstract: 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.
authors.affiliation: Department of Surgery, Clinical Science Institute, University College Hospital, Galway, Ireland.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Colleran
authors.forename: Niall
authors.initials: N
authors.lastname: McInerney
authors.forename: Andrew
authors.initials: A
authors.lastname: Rowan
authors.forename: Ella
authors.initials: E
authors.lastname: Barclay
authors.forename: Angela M
authors.initials: AM
authors.lastname: Jones
authors.forename: Catherine
authors.initials: C
authors.lastname: Curran
authors.forename: Nicola
authors.initials: N
authors.lastname: Miller
authors.forename: Michael
authors.initials: M
authors.lastname: Kerin
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Elinor
authors.initials: E
authors.lastname: Sawyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007494:Ireland; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human