title: TGFBR1(*)6A and Int7G24A variants of transforming growth factor-beta receptor 1 in Swedish familial and sporadic breast cancer.
abstract: Two common variants in transforming growth factor-beta receptor 1 (TGFBR1), TGFBR1(*)6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n=459) and in breast cancer patients from a familial cancer clinic (n=340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high- and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1(*)6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P=0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P=0.83 and 0.83, respectively). TGFBR1(*)6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01-5.11; P=0.049). These results indicate that the TGFBR1(*)6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Song
authors.forename: S
authors.initials: S
authors.lastname: Margolin
authors.forename: J
authors.initials: J
authors.lastname: Skoglund
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Rantala
authors.forename: S
authors.initials: S
authors.lastname: Picelli
authors.forename: B
authors.initials: B
authors.lastname: Werelius
authors.forename: A
authors.initials: A
authors.lastname: Lindblom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human