TY - JOUR
T1 - Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium
AU - Gaudet, Mia M
AU - Barrdahl, Myrto
AU - Lindström, Sara
AU - Travis, Ruth C
AU - Auer, Paul L.
AU - Buring, Julie E
AU - Chanock, Stephen J
AU - Heather Eliassen, A.
AU - Gapstur, Susan M.
AU - Giles, Graham G.
AU - Gunter, Marc
AU - Haiman, Christopher A
AU - Hunter, David J.
AU - Joshi, Amit D.
AU - Kaaks, Rudolf J
AU - Khaw, Kay-Tee
AU - Lee, I-Min
AU - Le Marchand, Loic
AU - Milne, Roger L
AU - Peeters, Petra H.M.
AU - Sund, Malin
AU - Tamimi, Rulla
AU - Trichopoulou, Antonia
AU - Weiderpass, Elisabete
AU - Yang, Xiaohong R
AU - Prentice, Ross L.
AU - Feigelson, Heather Spencer
AU - Canzian, Federico
AU - Kraft, Peter
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case–control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10−3 were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43–2.24; Pinteraction = 1.2 × 10−4) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
AB - Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case–control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10−3 were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43–2.24; Pinteraction = 1.2 × 10−4) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
KW - Breast cancer
KW - Genetic variation
KW - Menopausal hormone therapy
UR - http://www.scopus.com/inward/record.url?scp=84959107143&partnerID=8YFLogxK
U2 - 10.1007/s10549-016-3681-7
DO - 10.1007/s10549-016-3681-7
M3 - Article
C2 - 26802016
AN - SCOPUS:84959107143
VL - 155
SP - 531
EP - 540
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 3
ER -
