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Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort.
Breast Cancer Res 2006; 8(2):R22BC

Abstract

INTRODUCTION

Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region.

METHOD

We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls).

RESULTS

We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00-2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02-2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88-1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37-0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer.

CONCLUSION

Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women.

Authors+Show Affiliations

Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia, USA. eric.jacobs@cancer.orgNo 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

Language

eng

PubMed ID

16613616

Citation

Jacobs, Eric J., et al. "Polymorphisms in the Vascular Endothelial Growth Factor Gene and Breast Cancer in the Cancer Prevention Study II Cohort." Breast Cancer Research : BCR, vol. 8, no. 2, 2006, pp. R22.
Jacobs EJ, Feigelson HS, Bain EB, et al. Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. Breast Cancer Res. 2006;8(2):R22.
Jacobs, E. J., Feigelson, H. S., Bain, E. B., Brady, K. A., Rodriguez, C., Stevens, V. L., ... Calle, E. E. (2006). Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. Breast Cancer Research : BCR, 8(2), pp. R22.
Jacobs EJ, et al. Polymorphisms in the Vascular Endothelial Growth Factor Gene and Breast Cancer in the Cancer Prevention Study II Cohort. Breast Cancer Res. 2006;8(2):R22. PubMed PMID: 16613616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. AU - Jacobs,Eric J, AU - Feigelson,Heather Spencer, AU - Bain,Elizabeth B, AU - Brady,Kerri A, AU - Rodriguez,Carmen, AU - Stevens,Victoria L, AU - Patel,Alpa V, AU - Thun,Michael J, AU - Calle,Eugenia E, Y1 - 2006/04/13/ PY - 2005/11/11/received PY - 2006/02/13/revised PY - 2006/03/17/accepted PY - 2006/4/15/pubmed PY - 2006/8/1/medline PY - 2006/4/15/entrez SP - R22 EP - R22 JF - Breast cancer research : BCR JO - Breast Cancer Res. VL - 8 IS - 2 N2 - INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls). RESULTS: We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00-2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02-2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88-1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37-0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/16613616/Polymorphisms_in_the_vascular_endothelial_growth_factor_gene_and_breast_cancer_in_the_Cancer_Prevention_Study_II_cohort_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1400 DB - PRIME DP - Unbound Medicine ER -