TY - JOUR
T1 - Gene-environment interactions involving functional variants
T2 - Results from the Breast Cancer Association Consortium
AU - Barrdahl, Myrto
AU - Rudolph, Anja
AU - Hopper, John L
AU - Southey, Melissa C
AU - Broeks, Annegien
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Gago-Dominguez, Manuela
AU - Castelao, J Esteban
AU - Guénel, Pascal
AU - Truong, Thérèse
AU - Bojesen, Stig E
AU - Gapstur, Susan M
AU - Gaudet, Mia M
AU - Brenner, Hermann
AU - Arndt, Volker
AU - Brauch, Hiltrud
AU - Hamann, Ute
AU - Mannermaa, Arto
AU - Lambrechts, Diether
AU - Jongen, Lynn
AU - Flesch-Janys, Dieter
AU - Thoene, Kathrin
AU - Couch, Fergus J
AU - Giles, Graham G
AU - Simard, Jacques
AU - Goldberg, Mark S
AU - Figueroa, Jonine
AU - Michailidou, Kyriaki
AU - Bolla, Manjeet K
AU - Dennis, Joe
AU - Wang, Qin
AU - Eilber, Ursula
AU - Behrens, Sabine
AU - Czene, Kamila
AU - Hall, Per
AU - Cox, Angela
AU - Cross, Simon
AU - Swerdlow, Anthony
AU - Schoemaker, Minouk J
AU - Dunning, Alison M
AU - Kaaks, Rudolf
AU - Pharoah, Paul D P
AU - Schmidt, Marjanka
AU - Garcia-Closas, Montserrat
AU - Easton, Douglas F
AU - Milne, Roger L
AU - Chang-Claude, Jenny
N1 - © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene-environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67-0.88, pint = 1.8 × 10(-4) ). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16-1.59, pint = 1.9 × 10(-5) ) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12-1.43, pint =1.8 × 10(-4) ) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint = 0.89, 95% CI: 0.83-0.95, pint = 5.2 × 10(-4) ). While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed.
AB - Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene-environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67-0.88, pint = 1.8 × 10(-4) ). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16-1.59, pint = 1.9 × 10(-5) ) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12-1.43, pint =1.8 × 10(-4) ) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint = 0.89, 95% CI: 0.83-0.95, pint = 5.2 × 10(-4) ). While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed.
KW - Alcohol Drinking
KW - Breast Neoplasms
KW - CASP8 and FADD-Like Apoptosis Regulating Protein
KW - Estrogen Receptor alpha
KW - Female
KW - Gene-Environment Interaction
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Smoking
KW - Journal Article
U2 - 10.1002/ijc.30859
DO - 10.1002/ijc.30859
M3 - Journal article
C2 - 28670784
VL - 141
SP - 1830
EP - 1840
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 9
ER -