Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.
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Date
2014-05-26ICR Author
Author
Johnson, N
Dudbridge, F
Orr, N
Gibson, L
Jones, ME
Schoemaker, MJ
Folkerd, EJ
Haynes, BP
Hopper, JL
Southey, MC
Dite, GS
Apicella, C
Schmidt, MK
Broeks, A
Van't Veer, LJ
Atsma, F
Muir, K
Lophatananon, A
Fasching, PA
Beckmann, MW
Ekici, AB
Renner, SP
Sawyer, E
Tomlinson, I
Kerin, M
Miller, N
Burwinkel, B
Marme, F
Schneeweiss, A
Sohn, C
Guénel, P
Truong, T
Cordina, E
Menegaux, F
Bojesen, SE
Nordestgaard, BG
Flyger, H
Milne, R
Zamora, MP
Arias Perez, JI
Benitez, J
Bernstein, L
Anton-Culver, H
Ziogas, A
Clarke Dur, C
Brenner, H
Müller, H
Arndt, V
Dieffenbach, AK
Meindl, A
Heil, J
Bartram, CR
Schmutzler, RK
Brauch, H
Justenhoven, C
Ko, Y-D
GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network,
Nevanlinna, H
Muranen, TA
Aittomäki, K
Blomqvist, C
Matsuo, K
Dörk, T
Bogdanova, NV
Antonenkova, NN
Lindblom, A
Mannermaa, A
Kataja, V
Kosma, V-M
Hartikainen, JM
Chenevix-Trench, G
Beesley, J
kConFab Investigators,
Australian Ovarian Cancer Study Group,
Wu, AH
Van den Berg, D
Tseng, C-C
Lambrechts, D
Smeets, D
Neven, P
Wildiers, H
Chang-Claude, J
Rudolph, A
Nickels, S
Flesch-Janys, D
Radice, P
Peterlongo, P
Bonanni, B
Pensotti, V
Couch, FJ
Olson, JE
Wang, X
Fredericksen, Z
Pankratz, VS
Giles, GG
Severi, G
Baglietto, L
Haiman, C
Simard, J
Goldberg, MS
Labrèche, F
Dumont, M
Soucy, P
Teo, S
Yip, CH
Phuah, SY
Cornes, BK
Kristensen, VN
Grenaker Alnæs, G
Børresen-Dale, A-L
Zheng, W
Winqvist, R
Pylkäs, K
Jukkola-Vuorinen, A
Grip, M
Andrulis, IL
Knight, JA
Glendon, G
Mulligan, AM
Devillee, P
Figueroa, J
Chanock, SJ
Lissowska, J
Sherman, ME
Hall, P
Schoof, N
Hooning, M
Hollestelle, A
Oldenburg, RA
Tilanus-Linthorst, M
Liu, J
Cox, A
Brock, IW
Reed, MWR
Cross, SS
Blot, W
Signorello, LB
Pharoah, PDP
Dunning, AM
Shah, M
Kang, D
Noh, D-Y
Park, SK
Choi, J-Y
Hartman, M
Miao, H
Lim, WY
Tang, A
Hamann, U
Försti, A
Rüdiger, T
Ulmer, HU
Jakubowska, A
Lubinski, J
Jaworska-Bieniek, K
Durda, K
Sangrajrang, S
Gaborieau, V
Brennan, P
McKay, J
Slager, S
Toland, AE
Vachon, C
Yannoukakos, D
Shen, C-Y
Yu, J-C
Huang, C-S
Hou, M-F
González-Neira, A
Tessier, DC
Vincent, D
Bacot, F
Luccarini, C
Dennis, J
Michailidou, K
Bolla, MK
Wang, J
Easton, DF
García-Closas, M
Dowsett, M
Ashworth, A
Swerdlow, AJ
Peto, J
dos Santos Silva, I
Fletcher, O
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network
kConFab Investigators
Australian Ovarian Cancer Study Group
Humans
Breast Neoplasms
Genetic Predisposition to Disease
Reproductive History
Risk Factors
Age Factors
Age of Onset
Premenopause
Menarche
Genotype
Polymorphism, Single Nucleotide
Adult
Aged
Middle Aged
European Continental Ancestry Group
Female
Cytochrome P-450 CYP3A
Genetic Association Studies
Research team
Complex Trait Genetics
Functional Genetic Epidemiology
Molecular Epidemiology
Aetiological Epidemiology
Endocrinology
Gene Function
Language
eng
Date accepted
2014-04-24
License start date
2014-05-26
Citation
Breast cancer research : BCR, 2014, 16 (3), pp. R51 - ?
Publisher
BMC
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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