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Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study
- Source :
- Breast Cancer Research, 16(3). BioMed Central Ltd., Breast Cancer Research, 16, 3, pp. R51, Breast Cancer Research; 16(R51), pp 1-13 (2014), Breast Cancer Research : BCR, Breast Cancer Research, 16, R51, Orr, N 2014, ' Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study ', Breast Cancer Research, vol. 16 . https://doi.org/10.1186/bcr3662
- Publication Year :
- 2014
- Publisher :
- BioMed Central Ltd., 2014.
-
Abstract
- Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (Ptrend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; Ptrend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; Ptrend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.
- Subjects :
- Physiology
chemistry.chemical_compound
610 Medical sciences Medicine
0302 clinical medicine
Risk Factors
Medizinische Fakultät
Genotype
Cytochrome P-450 CYP3A
Age of Onset
Reproductive History
Medicine(all)
0303 health sciences
Age Factors
twins
Middle Aged
3. Good health
steroid-hormones
030220 oncology & carcinogenesis
loci
Menarche
Veterinary (all)
Female
Research Article
Adult
medicine.medical_specialty
premenopausal women
Breast Neoplasms
Estrone
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
White People
Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
03 medical and health sciences
Breast cancer
SDG 3 - Good Health and Well-being
estradiol
medicine
Humans
Genetic Predisposition to Disease
ddc:610
Genetic Association Studies
Aged
030304 developmental biology
Gynecology
business.industry
Case-control study
medicine.disease
Clinical research
Premenopause
chemistry
sex-hormone levels
Cancer and Oncology
genome-wide association
Age of onset
business
serum
Subjects
Details
- ISSN :
- 1465542X, 14655411, and 17510147
- Volume :
- 16
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research
- Accession number :
- edsair.doi.dedup.....c705ebdb2963a54b7d0c6ad8dae73485