TGFBR1*6A and cancer risk: A meta-analysis of seven case-control studies Journal Article


Authors: Kaklamani, V. G.; Hou, N.; Bian, Y.; Reich, J.; Offit, K.; Michel, L. S. ; Rubinstein, W. S.; Rademaker, A.; Pasche, B.
Article Title: TGFBR1*6A and cancer risk: A meta-analysis of seven case-control studies
Abstract: Purpose: TGFBR1*6A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1). TGFBR1*6A is a candidate tumor susceptibility allele that has been associated with an increased incidence of various types of cancer. This study was undertaken to analyze all published case-control studies on TGFBR1*6A and cancer and determine whether TGFBR1*6A is associated with cancer. Patients and Methods: All published case-control studies assessing the germline frequency of TGFBR1*6A were included. Studies assessing TGFBR1*6A in tumors were excluded. The results of seven studies comprising 2,438 cases and 1,846 controls were pooled and analyzed. Results: Overall, TGFBR1*6A carriers have a 26% increased risk of cancer (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.07 to 1.49). Cancer risk for TGFBR1*6A homozygotes (OR, 2.53; 95% CI, 1.39 to 4.61) is twice that of TGFBR1*6A heterozygotes (OR, 1.26; 95% CI, 1.04 to 1.51). Analysis of various types of tumors shows that TGFBR1*6A carriers are at increased risk of developing breast cancer (OR, 1.48; 95% CI, 1.11 to 1.96), hematological malignancies (OR, 1.70; 95% CI, 1.13 to 2.54), and ovarian cancer (OR, 1.53; 95% CI, 1.07 to 2.17). Carriers of TGFBR1*6A. who are from the United States are at increased risk of colorectal cancer (OR, 1.38; 95% CI, 1.02 to 1.86). However, Southern European TGFBR1*6A. carriers have no increased colorectal cancer risk. There is no association between TGFBR1*6A and bladder cancer. Conclusion: TGFBR1*6A is emerging as a high-frequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies. © 2003 by American Society of Clinical Oncology.
Keywords: adolescent; adult; aged; middle aged; case control study; genetics; case-control studies; clinical trial; cancer risk; neoplasm; neoplasms; colorectal cancer; metabolism; allele; cancer susceptibility; genetic predisposition to disease; ovary cancer; breast cancer; transforming growth factor beta; genetic association; genotype; alleles; odds ratio; heterozygote; bladder cancer; risk; hematologic malignancy; systematic review; homozygote; transforming growth factor beta receptor; receptors, transforming growth factor beta; genetic predisposition; race difference; polymorphism, genetic; meta analysis; genetic polymorphism; transforming growth factor beta receptor 1; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 17
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-09-01
Start Page: 3236
End Page: 3243
Language: English
DOI: 10.1200/jco.2003.11.524
PUBMED: 12947057
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    509 Offit
  2. Loren Michel
    14 Michel