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Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk.
Cancer Res. 2005 Apr 15; 65(8):3454-61.CR

Abstract

There is growing evidence that common variants of the transforming growth factor-beta (TGF-beta) signaling pathway may modify breast cancer risk. In vitro studies have shown that some variants increase TGF-beta 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-beta circulating levels. Cases and controls were of similar ethnicity and geographic location. Thirty percent of cases were identified as high or low TGF-beta 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-beta 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-beta 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.

Authors+Show Affiliations

Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 North St. Clair Street, Chicago, IL 60611, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15833881

Citation

Kaklamani, Virginia G., et al. "Combined Genetic Assessment of Transforming Growth Factor-beta Signaling Pathway Variants May Predict Breast Cancer Risk." Cancer Research, vol. 65, no. 8, 2005, pp. 3454-61.
Kaklamani VG, Baddi L, Liu J, et al. Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Cancer Res. 2005;65(8):3454-61.
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. (2005). Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Cancer Research, 65(8), 3454-61.
Kaklamani VG, et al. Combined Genetic Assessment of Transforming Growth Factor-beta Signaling Pathway Variants May Predict Breast Cancer Risk. Cancer Res. 2005 Apr 15;65(8):3454-61. PubMed PMID: 15833881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. AU - Kaklamani,Virginia G, AU - Baddi,Lisa, AU - Liu,Junjian, AU - Rosman,Diana, AU - Phukan,Sharbani, AU - Bradley,Ciarán, AU - Hegarty,Chris, AU - McDaniel,Bree, AU - Rademaker,Alfred, AU - Oddoux,Carole, AU - Ostrer,Harry, AU - Michel,Loren S, AU - Huang,Helen, AU - Chen,Yu, AU - Ahsan,Habibul, AU - Offit,Kenneth, AU - Pasche,Boris, PY - 2005/4/19/pubmed PY - 2005/6/4/medline PY - 2005/4/19/entrez SP - 3454 EP - 61 JF - Cancer research JO - Cancer Res VL - 65 IS - 8 N2 - There is growing evidence that common variants of the transforming growth factor-beta (TGF-beta) signaling pathway may modify breast cancer risk. In vitro studies have shown that some variants increase TGF-beta 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-beta circulating levels. Cases and controls were of similar ethnicity and geographic location. Thirty percent of cases were identified as high or low TGF-beta 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-beta 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-beta 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15833881/Combined_genetic_assessment_of_transforming_growth_factor_beta_signaling_pathway_variants_may_predict_breast_cancer_risk_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15833881 DB - PRIME DP - Unbound Medicine ER -