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

Stefan Nickels; Thérèse Truong; Rebecca Hein; Kristen Stevens; Katharina Buck; Sabine Behrens; Ursula Eilber; Martina Schmidt; Lothar Häberle; Alina Vrieling; Mia Gaudet; Jonine Figueroa; Nils Schoof; Amanda B Spurdle; Anja Rudolph; Peter A Fasching; John L Hopper; Enes Makalic; Daniel F Schmidt; Melissa C Southey; Matthias W Beckmann; Arif B Ekici; Olivia Fletcher; Lorna Gibson; Isabel dos Santos Silva; Julian Peto; Manjeet K Humphreys; Jean Wang; Emilie Cordina-Duverger; Florence Menegaux; Børge G Nordestgaard; Stig E Bojesen; Charlotte Lanng; Hoda Anton-Culver; Argyrios Ziogas; Leslie Bernstein; Christina A Clarke; Hermann Brenner; Heiko Müller; Volker Arndt; Christa Stegmaier; Hiltrud Brauch; Thomas Brüning; Volker Harth; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Diether Lambrechts; Dominiek Smeets; GENICA Network

doi:10.1371/journal.pgen.1003284

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

Stefan Nickels, Thérèse Truong, Rebecca Hein, Kristen Stevens, Katharina Buck, Sabine Behrens, Ursula Eilber, Martina Schmidt, Lothar Häberle, Alina Vrieling, Mia Gaudet, Jonine Figueroa, Nils Schoof, Amanda B Spurdle, Anja Rudolph, Peter A Fasching, John L Hopper, Enes Makalic, Daniel F Schmidt, Melissa C SoutheyMatthias W Beckmann, Arif B Ekici, Olivia Fletcher, Lorna Gibson, Isabel dos Santos Silva, Julian Peto, Manjeet K Humphreys, Jean Wang, Emilie Cordina-Duverger, Florence Menegaux, Børge G Nordestgaard, Stig E Bojesen, Charlotte Lanng, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Hiltrud Brauch, Thomas Brüning, Volker Harth, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Diether Lambrechts, Dominiek Smeets, GENICA Network

110 Citations (Scopus)

Abstract

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 (P_interaction = 2.4×10^-6) and between CASP8-rs17468277 and alcohol consumption (P_interaction = 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 (P_interaction = 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.

Original language	English
Journal	P L o S Genetics (Online)
Volume	9
Issue number	3
Pages (from-to)	e1003284
ISSN	1553-7404
DOIs	https://doi.org/10.1371/journal.pgen.1003284
Publication status	Published - Mar 2013

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Nickels, S., Truong, T., Hein, R., Stevens, K., Buck, K., Behrens, S., Eilber, U., Schmidt, M., Häberle, L., Vrieling, A., Gaudet, M., Figueroa, J., Schoof, N., Spurdle, A. B., Rudolph, A., Fasching, P. A., Hopper, J. L., Makalic, E., Schmidt, D. F., ... GENICA Network (2013). Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. P L o S Genetics (Online), 9(3), e1003284. https://doi.org/10.1371/journal.pgen.1003284

Nickels, S, Truong, T, Hein, R, Stevens, K, Buck, K, Behrens, S, Eilber, U, Schmidt, M, Häberle, L, Vrieling, A, Gaudet, M, Figueroa, J, Schoof, N, Spurdle, AB, Rudolph, A, Fasching, PA, Hopper, JL, Makalic, E, Schmidt, DF, Southey, MC, Beckmann, MW, Ekici, AB, Fletcher, O, Gibson, L, Silva, IDS, Peto, J, Humphreys, MK, Wang, J, Cordina-Duverger, E, Menegaux, F, Nordestgaard, BG, Bojesen, SE, Lanng, C, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Müller, H, Arndt, V, Stegmaier, C, Brauch, H, Brüning, T, Harth, V, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Lambrechts, D, Smeets, D & GENICA Network 2013, 'Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors', P L o S Genetics (Online), vol. 9, no. 3, pp. e1003284. https://doi.org/10.1371/journal.pgen.1003284

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abstract = "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.",

author = "Stefan Nickels and Th{\'e}r{\`e}se Truong and Rebecca Hein and Kristen Stevens and Katharina Buck and Sabine Behrens and Ursula Eilber and Martina Schmidt and Lothar H{\"a}berle and Alina Vrieling and Mia Gaudet and Jonine Figueroa and Nils Schoof and Spurdle, {Amanda B} and Anja Rudolph and Fasching, {Peter A} and Hopper, {John L} and Enes Makalic and Schmidt, {Daniel F} and Southey, {Melissa C} and Beckmann, {Matthias W} and Ekici, {Arif B} and Olivia Fletcher and Lorna Gibson and Silva, {Isabel dos Santos} and Julian Peto and Humphreys, {Manjeet K} and Jean Wang and Emilie Cordina-Duverger and Florence Menegaux and Nordestgaard, {B{\o}rge G} and Bojesen, {Stig E} and Charlotte Lanng and Hoda Anton-Culver and Argyrios Ziogas and Leslie Bernstein and Clarke, {Christina A} and Hermann Brenner and Heiko M{\"u}ller and Volker Arndt and Christa Stegmaier and Hiltrud Brauch and Thomas Br{\"u}ning and Volker Harth and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M} and Diether Lambrechts and Dominiek Smeets and B{\o}rge Nordestgaard",

year = "2013",

month = mar,

doi = "10.1371/journal.pgen.1003284",

language = "English",

volume = "9",

pages = "e1003284",

journal = "P L o S Genetics",

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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 - GENICA Network

PY - 2013/3

Y1 - 2013/3

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.

U2 - 10.1371/journal.pgen.1003284

DO - 10.1371/journal.pgen.1003284

M3 - Journal article

C2 - 23544014

SN - 1553-7390

VL - 9

SP - e1003284

JO - P L o S Genetics

JF - P L o S Genetics

IS - 3

ER -

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

Abstract

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