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The estrogen receptor alpha gene and breast cancer risk (The Netherlands).
Cancer Causes Control. 2005 Dec; 16(10):1195-202.CC

Abstract

OBJECTIVE

In this study we aimed to investigate whether the PvuII, XbaI and B-variant polymorphisms in the estrogen receptor alpha gene (ER-alpha) are associated with an increased risk of breast cancer in postmenopausal women, and whether the effect of high estradiol (E2) levels on breast cancer risk is altered by these polymorphisms. The selection of these polymorphisms was based on previously published associations with osteoporosis and spontaneous abortions.

METHODS

The effect of the three polymorphisms on breast cancer risk was studied using a case-cohort design nested within a large population-based cohort study (n = 9349) in the Netherlands (the DOM-cohort). In total 380 incident breast cancer cases and a subcohort of 422 women were genotyped by RFLP or ASO hybridization methods.

RESULTS

Women with the PvuII pp genotype had a 1.5 times non significant increased risk of breast cancer (95% CI: 0.94-2.42; p(trend) = 0.09) compared to women with the PP genotype. The Pp or pp genotype in combination with high E2 levels raised breast cancer risk significantly when compared to women with low E2 levels and the PP genotype (RR=2.26; 95% CI: 1.24-4.13). This interaction was statistically significant on the multiplicative scale (p = 0.01). The XbaI genotype (RR(xx versus XX) = 1.19; 95% CI: 0.73-1.95) and the B' allele (RR(BB'+B'B' versus BB) = 0.87; 95% CI: 0.56-1.33) were not associated with breast cancer risk.

CONCLUSION

The results of this study suggest that the PvuII polymorphism in the ER-alpha, or another mutation in linkage disequilibrium with PvuII, in combination with high E2 levels increases breast cancer risk in postmenopausal women.

Authors+Show Affiliations

Julius Center for Health Sciences and Primary Care, UMC Utrecht, Room St. 6.131, PO Box 85500, 3508, GA Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16215870

Citation

Onland-Moret, N Charlotte, et al. "The Estrogen Receptor Alpha Gene and Breast Cancer Risk (The Netherlands)." Cancer Causes & Control : CCC, vol. 16, no. 10, 2005, pp. 1195-202.
Onland-Moret NC, van Gils CH, Roest M, et al. The estrogen receptor alpha gene and breast cancer risk (The Netherlands). Cancer Causes Control. 2005;16(10):1195-202.
Onland-Moret, N. C., van Gils, C. H., Roest, M., Grobbee, D. E., & Peeters, P. H. (2005). The estrogen receptor alpha gene and breast cancer risk (The Netherlands). Cancer Causes & Control : CCC, 16(10), 1195-202.
Onland-Moret NC, et al. The Estrogen Receptor Alpha Gene and Breast Cancer Risk (The Netherlands). Cancer Causes Control. 2005;16(10):1195-202. PubMed PMID: 16215870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The estrogen receptor alpha gene and breast cancer risk (The Netherlands). AU - Onland-Moret,N Charlotte, AU - van Gils,Carla H, AU - Roest,Mark, AU - Grobbee,Diederick E, AU - Peeters,Petra H M, PY - 2004/12/23/received PY - 2005/06/22/accepted PY - 2005/10/11/pubmed PY - 2006/3/1/medline PY - 2005/10/11/entrez SP - 1195 EP - 202 JF - Cancer causes & control : CCC JO - Cancer Causes Control VL - 16 IS - 10 N2 - OBJECTIVE: In this study we aimed to investigate whether the PvuII, XbaI and B-variant polymorphisms in the estrogen receptor alpha gene (ER-alpha) are associated with an increased risk of breast cancer in postmenopausal women, and whether the effect of high estradiol (E2) levels on breast cancer risk is altered by these polymorphisms. The selection of these polymorphisms was based on previously published associations with osteoporosis and spontaneous abortions. METHODS: The effect of the three polymorphisms on breast cancer risk was studied using a case-cohort design nested within a large population-based cohort study (n = 9349) in the Netherlands (the DOM-cohort). In total 380 incident breast cancer cases and a subcohort of 422 women were genotyped by RFLP or ASO hybridization methods. RESULTS: Women with the PvuII pp genotype had a 1.5 times non significant increased risk of breast cancer (95% CI: 0.94-2.42; p(trend) = 0.09) compared to women with the PP genotype. The Pp or pp genotype in combination with high E2 levels raised breast cancer risk significantly when compared to women with low E2 levels and the PP genotype (RR=2.26; 95% CI: 1.24-4.13). This interaction was statistically significant on the multiplicative scale (p = 0.01). The XbaI genotype (RR(xx versus XX) = 1.19; 95% CI: 0.73-1.95) and the B' allele (RR(BB'+B'B' versus BB) = 0.87; 95% CI: 0.56-1.33) were not associated with breast cancer risk. CONCLUSION: The results of this study suggest that the PvuII polymorphism in the ER-alpha, or another mutation in linkage disequilibrium with PvuII, in combination with high E2 levels increases breast cancer risk in postmenopausal women. SN - 0957-5243 UR - https://www.unboundmedicine.com/medline/citation/16215870/The_estrogen_receptor_alpha_gene_and_breast_cancer_risk__The_Netherlands__ L2 - https://doi.org/10.1007/s10552-005-0307-5 DB - PRIME DP - Unbound Medicine ER -