TGFBR16A and Int7G24A variants of transforming growth factor-[beta] receptor 1 in Swedish familial and sporadic breast cancer

• Published in: British journal of cancer 2007-10, Vol.97 (8), p.1175
• Main Authors: Song, B, Margolin, S, Skoglund, J, Zhou, X, Rantala, J, Picelli, S, Werelius, B, Lindblom, A
• Format: Article
• Language: English
• Subjects: Breast cancer; Cancer research; Family medical history; Genomics; Growth factors; Hospitals; Medical research; Mutation; Oncology
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603961

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.