TGFBR16A and Cancer Risk: A Meta-Analysis of Seven Case-Control Studies

• Published in: Journal of clinical oncology Vol. 21; no. 17; pp. 3236 - 3243
• Main Authors: Kaklamani, Virginia G, Hou, Nanjiang, Bian, Yiansong, Reich, Jennifer, Offit, Kenneth, Michel, Loren S, Rubinstein, W S, Rademaker, Alfred, Pasche, Boris
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-09-2003; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Alleles; Antineoplastic agents; Biological and medical sciences; Case-Control Studies; Chemotherapy; Female; Genetic Predisposition to Disease - genetics; Genotype; Heterozygote; Homozygote; Humans; Male; Medical sciences; Middle Aged; Neoplasms - genetics; Odds Ratio; Pharmacology. Drug treatments; Polymorphism, Genetic; Receptors, Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Tropical medicine; Central America; Netherlands; United States; Europe; America; West Indies; United Kingdom; Jamaica; North America; Human; Transforming growth factor; Cytokine; Case control study; Malignant tumor; Epidemiology; Metaanalysis; Membrane receptor; Gene; Polypeptide; Low; Gene penetrance; Risk factor; Genetics; Public health; Growth factor; Biological receptor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2003.11.524

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.
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.
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.
TGFBR1*6A is emerging as a highfrequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies.