Evidence From Humans
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Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study
Wedren, S., Lovmar, L., Humphreys, K., Magnusson, C., Melhus, H., Syvanen, A. C., Kindmark, A., Landegren, U., Fermer, M. L., Stiger, F., Persson, I., Baron, J., Weiderpass, E. Breast Cancer Research. 2004. 6:4, .
Topic area
Body size - Genetic variability
Study design
Population based case-control study
Funding agency
NIH, DOD, K&A Wallenberg Foundation
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Post menopausal
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Incident cases of primary invasive BC identified through regional cancer registries. Population controls randomly selected from Total Population Register and frequency matched by age.
Comment about participation selection
Cases also included women who had taken HRT or who reported diabetes mellitus Controls included 345 women who were enrolled in an endometrial cancer study
Exposure Investigated
Exposures investigated
BMI, ESR1 allele frequencies, used PCR-RFLP
How exposure was measured
Biological Questionnaire, self-administered
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Adequately controlled
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
Description of major analysis
Logistic regression analysis of ESR1 genotype and breast cancer, including effect modification by BMI
Strength of associations reported
In age-adjusted models, no strong relations between single nucleotide polymorphisms and BC risk
Haplotype analysis revealed significant associations modified by BMI; Across all women, carrying one copy (versus none) of the c.454-351AàG and c.975CàG type (AC) resulted in OR=1.19 (CI: 1.06-1.33); Across all women, carrying one copy (versus none) of the c.454-397CàT and c.975CàG type (TC) resulted in OR=1.19 (CI: 1.06-1.33)
For AC type in women with BMI <25, OR=1.04 (CI: 0.89-1.23); BMI 25-<28, OR=1.32 (CI: 1.0-1.64); BMI>=28, OR=1.41 (CI: 1.12-1.77); BMI>30, OR=1.48 (CI: 1.08-2.03); BMI>32. OR=1.60 (CI: 1.02-2.49)
For TC type in women with BMI <25, 1.08 (CI: 0.91-1.27); BMI 25-<28, OR=1.21 (CI: 0.97-1.51); BMI >=28, OR=1.48 (CI: 1.17-1.88), BMI>30, OR=1.59 (CI: 1.15-2.21), and BMI>32 OR=1.71 (CI: 1.08-2.70)
INTRODUCTION: Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk. METHODS: We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. RESULTS: There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. CONCLUSION: We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.
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