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Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers.
- Source :
-
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2015 Apr; Vol. 24 (4), pp. 698-707. Date of Electronic Publication: 2015 Jan 22. - Publication Year :
- 2015
-
Abstract
- Background: Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype-phenotype correlation has been found in both genes, and the effect of reproductive factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.<br />Methods: We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.<br />Results: We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.<br />Conclusions: As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the "high-risk" zones.<br />Impact: Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers.<br /> (©2015 American Association for Cancer Research.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Female
Genetic Predisposition to Disease
Heterozygote
Humans
Menarche
Menopause
Middle Aged
Proportional Hazards Models
Reproductive History
Risk Factors
Young Adult
BRCA1 Protein genetics
BRCA2 Protein genetics
Breast Neoplasms epidemiology
Breast Neoplasms genetics
Estrogens adverse effects
Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7755
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 25613119
- Full Text :
- https://doi.org/10.1158/1055-9965.EPI-14-0884