Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

TY - JOUR

T1 - Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

AU - Nickels, Stefan

AU - Truong, Thérèse

AU - Hein, Rebecca

AU - Stevens, Kristen

AU - Buck, Katharina

AU - Behrens, Sabine

AU - Eilber, Ursula

AU - Schmidt, Martina

AU - Häberle, Lothar

AU - Vrieling, Alina

AU - Gaudet, Mia

AU - Figueroa, Jonine

AU - Schoof, Nils

AU - Spurdle, Amanda B

AU - Rudolph, Anja

AU - Fasching, Peter A

AU - Hopper, John L

AU - Makalic, Enes

AU - Schmidt, Daniel F

AU - Southey, Melissa C

AU - Beckmann, Matthias W

AU - Ekici, Arif B

AU - Fletcher, Olivia

AU - Gibson, Lorna

AU - Silva, Isabel dos Santos

AU - Peto, Julian

AU - Humphreys, Manjeet K

AU - Wang, Jean

AU - Cordina-Duverger, Emilie

AU - Menegaux, Florence

AU - Nordestgaard, Børge G

AU - Bojesen, Stig E

AU - Lanng, Charlotte

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Bernstein, Leslie

AU - Clarke, Christina A

AU - Brenner, Hermann

AU - Müller, Heiko

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Harth, Volker

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Hartikainen, Jaana M

AU - Lambrechts, Diether

AU - Smeets, Dominiek

AU - Neven, Patrick

AU - Paridaens, Robert

AU - Flesch-Janys, Dieter

AU - Obi-Osius, Nadia

AU - Wang-Gohrke, Shan

AU - Couch, Fergus J

AU - Olson, Janet E

AU - Vachon, Celine M

AU - Giles, Graham G

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - Offit, Kenneth

AU - John, Esther M

AU - Miron, Alexander

AU - Andrulis, Irene L

AU - Knight, Julia A

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Chanock, Stephen J

AU - Lissowska, Jolanta

AU - Liu, Jianjun

AU - Cox, Angela

AU - Cramp, Helen

AU - Connley, Dan

AU - Balasubramanian, Sabapathy

AU - Dunning, Alison M

AU - Shah, Mitul

AU - Trentham-Dietz, Amy

AU - Newcomb, Polly

AU - Titus, Linda

AU - Egan, Kathleen

AU - Cahoon, Elizabeth K

AU - Rajaraman, Preetha

AU - Sigurdson, Alice J

AU - Doody, Michele M

AU - Guénel, Pascal

AU - Pharoah, Paul D P

AU - Schmidt, Marjanka K

AU - Hall, Per

AU - Easton, Doug F

AU - Garcia-Closas, Montserrat

AU - Milne, Roger L

AU - Chang-Claude, Jenny

AU - GENICA Network

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

AB - Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

KW - Alleles

KW - Breast Neoplasms

KW - Caspase 8

KW - European Continental Ancestry Group

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Microfilament Proteins

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1371/journal.pgen.1003284

DO - 10.1371/journal.pgen.1003284

M3 - SCORING: Journal article

C2 - 23544014

VL - 9

SP - e1003284

JO - PLOS GENET

JF - PLOS GENET

SN - 1553-7404

IS - 3

ER -