Combined genetic assessment of transforming growth factor-β signaling pathway variants may predict breast cancer risk Journal Article

  

Authors:	Kaklamani, V. G.; Baddi, L.; Liu, J.; Rosman, D.; Phukan, S.; Bradley, C.; Hegarty, C.; McDaniel, B.; Rademaker, A.; Oddoux, C.; Ostrer, H.; Michel, L. S.; Huang, H.; Chen, Y.; Ahsan, H.; Offit, K.; Pasche, B.
Article Title:	Combined genetic assessment of transforming growth factor-β signaling pathway variants may predict breast cancer risk
Abstract:	There is growing evidence that common variants of the transforming growth factor-β (TGF-β) signaling pathway may modify breast cancer risk. In vitro studies have shown that some variants increase TGF-β signaling, whereas others have an opposite effect. We tested the hypothesis that a combined genetic assessment of two well-characterized variants may predict breast cancer risk. Consecutive patients (n = 660) with breast cancer from the Memorial Sloan-Kettering Cancer Center (New York, NY) and healthy females (n = 880) from New York City were genotyped for the hypomorphic TGFBR1*6A allele and for the TGFB1 T29C variant that results in increased TGF-β circulating levels. Cases and controls were of similar ethnicity and geographic location. Thirty percent of cases were identified as high or low TGF-β signalers based on TGFB1 and TGFBR1 genotypes. There was a significantly higher proportion of high signalers (TGFBR1/TGFBR1 and TGFB1*CC) among controls (21.6%) than cases (15.7%; P = 0.003). The odds ratio [OR; 95% confidence interval (95% CI)] for individuals with the lowest expected TGF-β signaling level (TGFB1*TT or TGFB1*TC and TGFBR1*6A) was 1.69 (1.08-2.66) when compared with individuals with the highest expected TGF-signaling levels. Breast cancer risk incurred by low signalers was most pronounced among women after age 50 years (OR, 2.05; 95% CI, 1.01-4.16). TGFBR1*6A was associated with a significantly increased risk for breast cancer (OR, 1.46; 95% CI, 1.04-2.06), but the TGFB1*CC genotype was not associated with any appreciable risk (OR, 0.89; 95% CI, 0.63-1.21). TGFBR1*6A effect was most pronounced among women diagnosed after age 50 years (OR, 2.20; 95% CI, 1.25-3.87). This is the first study assessing the TGF-β signaling pathway through two common and functionally relevant TGFBR1 and TGFB1 variants. This approach may predict breast cancer risk in a large subset of the population. ©2005 American Association for Cancer Research.
Keywords:	signal transduction; adult; controlled study; human tissue; aged; middle aged; major clinical study; case-control studies; cancer risk; comparative study; neoplasm staging; genetic analysis; genetic predisposition to disease; breast cancer; transforming growth factor beta; genotype; alleles; breast neoplasms; transforming growth factor beta receptor; transforming growth factor beta1; receptors, transforming growth factor beta; receptors, estrogen; receptors, progesterone; protein variant; ethnology; geographic distribution; activin receptors, type i
Journal Title:	Cancer Research
Volume:	65
Issue:	8
ISSN:	0008-5472
Publisher:	American Association for Cancer Research
Date Published:	2005-04-01
Start Page:	3454
End Page:	3461
Language:	English
PUBMED:	15833881
PROVIDER:	scopus
DOI:	10.1158/0008-5472.CAN-04-2961
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-20244383746&partnerID=40&md5=e5de0545a9f798c7009fce6b5dfc4800
Notes:	--- - "Cited By (since 1996): 49" - "Export Date: 24 October 2012" - "CODEN: CNREA" - "Source: Scopus"

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