|Title:||Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: A case-control study||Authors:||Johnson N.
Van't Veer L.J.
Van den Berg D.
The GENICA (Gene Environment Interaction
Breast Cancer in Germany) Network, kConFab Investigators, Australian Ovarian Cancer Study Group
|Issue Date:||2014||Journal Volume:||16||Journal Issue:||1||Start page/Pages:||R51||Source:||Breast Cancer Research||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. ? 2014 Johnson et al.
|DOI:||10.1186/bcr3662||SDG/Keyword:||cytochrome P450 3A; estrogen receptor; progesterone receptor; cytochrome P450 3A; adult; age; allele; Article; breast cancer; cancer risk; case control study; controlled study; CYP3A gene; ethnicity; female; gene frequency; genetic association; genetic variation; genotype; heterozygote; homozygote; human; major clinical study; menarche; middle aged; single nucleotide polymorphism; age; aged; breast tumor; Caucasian; genetic association study; genetic predisposition; genetics; menarche; onset age; pathology; premenopause; reproductive history; risk factor; Adult; Age Factors; Age of Onset; Aged; Breast Neoplasms; Cytochrome P-450 CYP3A; European Continental Ancestry Group; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Menarche; Middle Aged; Polymorphism, Single Nucleotide; Premenopause; Reproductive History; Risk Factors
|Appears in Collections:||醫學系|
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