TY - JOUR
T1 - Genetic variation at CYP3A is associated with age at menarche and breast cancer risk
T2 - a case-control study
AU - GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network
AU - Johnson, Nichola
AU - Dudbridge, Frank
AU - Orr, Nick
AU - Gibson, Lorna
AU - Jones, Michael E
AU - Schoemaker, Minouk J
AU - Folkerd, Elizabeth J
AU - Haynes, Ben P
AU - Hopper, John L
AU - Southey, Melissa C
AU - Dite, Gillian S
AU - Apicella, Carmel
AU - Schmidt, Marjanka K
AU - Broeks, Annegien
AU - Van't Veer, Laura J
AU - Atsma, Femke
AU - Muir, Kenneth
AU - Lophatananon, Artitaya
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Ekici, Arif B
AU - Renner, Stefan P
AU - Sawyer, Elinor
AU - Tomlinson, Ian
AU - Kerin, Michael
AU - Miller, Nicola
AU - Burwinkel, Barbara
AU - Marme, Frederik
AU - Schneeweiss, Andreas
AU - Sohn, Christof
AU - Guénel, Pascal
AU - Truong, Therese
AU - Cordina, Emilie
AU - Menegaux, Florence
AU - Bojesen, Stig E
AU - Nordestgaard, Børge G
AU - Flyger, Henrik
AU - Milne, Roger
AU - Zamora, M Pilar
AU - Arias Perez, Jose Ignacio
AU - Benitez, Javier
AU - Bernstein, Leslie
AU - Anton-Culver, Hoda
AU - Ziogas, Argyrios
AU - Clarke Dur, Christina
AU - Brenner, Hermann
AU - Müller, Heiko
AU - Arndt, Volker
AU - Dieffenbach, Aida Karina
AU - Figueroa, Jonine
PY - 2014
Y1 - 2014
N2 - 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 (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 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 (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 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.
AB - 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 (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 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 (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 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.
KW - Adult
KW - Age Factors
KW - Age of Onset
KW - Aged
KW - Breast Neoplasms
KW - Cytochrome P-450 CYP3A
KW - European Continental Ancestry Group
KW - Female
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Menarche
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Premenopause
KW - Reproductive History
KW - Risk Factors
U2 - 10.1186/bcr3662
DO - 10.1186/bcr3662
M3 - Article
C2 - 24887515
SN - 1465-5411
VL - 16
SP - R51
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 3
ER -