1. Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer
- Author
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Julia H. Carter, Taiping Chen, Chad R. Jackson, Larry E. Douglass, Jeremy R. Graff, Bruce M. Colligan, James A. Deddens, Andrew Link, Jackson O. Pemberton, and Michael P. Markey
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Population ,Receptor, Transforming Growth Factor-beta Type I ,Breast Neoplasms ,Biology ,Protein Serine-Threonine Kinases ,Polymerase Chain Reaction ,Germline ,Breast cancer ,Germline mutation ,Risk Factors ,Carcinoma ,medicine ,Humans ,Neoplasm Invasiveness ,Allele ,education ,Germ-Line Mutation ,Polymorphism, Single-Stranded Conformational ,Aged ,Sequence Deletion ,Aged, 80 and over ,education.field_of_study ,Carcinoma, Ductal, Breast ,Case-control study ,Cancer ,Genetic Variation ,Middle Aged ,medicine.disease ,Introns ,Carcinoma, Lobular ,Oncology ,Case-Control Studies ,Cancer research ,Disease Progression ,Female ,Activin Receptors, Type I ,Receptors, Transforming Growth Factor beta ,Polymorphism, Restriction Fragment Length - Abstract
Purpose: The transforming growth factor-β (TGF-β) signaling pathway has been frequently implicated in breast cancer. An intronic variant (Int7G24A) of TGF-β receptor type I (TGFBR1) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer. Experimental Design: Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion (TGFBR1*6A) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism. Results: The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls (P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers. Conclusion: These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer.
- Published
- 2006