Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium. Barrdahl, M., Rudolph, A., Hopper, J. L., Southey, M. C., Broeks, A., Fasching, P. A., Beckmann, M. W., Gago-Dominguez, M., Castelao, J. E., Guénel, P., Truong, T., Bojesen, S. E., Gapstur, S. M., Gaudet, M. M., Brenner, H., Arndt, V., Brauch, H., Hamann, U., Mannermaa, A., Lambrechts, D., Jongen, L., Flesch-Janys, D., Thoene, K., Couch, F. J., Giles, G. G., Simard, J., Goldberg, M. S., Figueroa, J., Michailidou, K., Bolla, M. K., Dennis, J., Wang, Q., Eilber, U., Behrens, S., Czene, K., Hall, P., Cox, A., Cross, S., Swerdlow, A., Schoemaker, M. J., Dunning, A. M., Kaaks, R., Pharoah, P. D. P., Schmidt, M., Garcia-Closas, M., Easton, D. F., Milne, R. L., & Chang-Claude, J. International Journal of Cancer, 141(9):1830–1840, 2017.
doi  abstract   bibtex   
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 \textless 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.
@article{barrdahl_gene-environment_2017,
	title = {Gene-environment interactions involving functional variants: {Results} from the {Breast} {Cancer} {Association} {Consortium}},
	volume = {141},
	issn = {1097-0215},
	shorttitle = {Gene-environment interactions involving functional variants},
	doi = {10.1002/ijc.30859},
	abstract = {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 {\textless} 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.},
	language = {eng},
	number = {9},
	journal = {International Journal of Cancer},
	author = {Barrdahl, Myrto and Rudolph, Anja and Hopper, John L. and Southey, Melissa C. and Broeks, Annegien and Fasching, Peter A. and Beckmann, Matthias W. and Gago-Dominguez, Manuela and Castelao, J. Esteban and Guénel, Pascal and Truong, Thérèse and Bojesen, Stig E. and Gapstur, Susan M. and Gaudet, Mia M. and Brenner, Hermann and Arndt, Volker and Brauch, Hiltrud and Hamann, Ute and Mannermaa, Arto and Lambrechts, Diether and Jongen, Lynn and Flesch-Janys, Dieter and Thoene, Kathrin and Couch, Fergus J. and Giles, Graham G. and Simard, Jacques and Goldberg, Mark S. and Figueroa, Jonine and Michailidou, Kyriaki and Bolla, Manjeet K. and Dennis, Joe and Wang, Qin and Eilber, Ursula and Behrens, Sabine and Czene, Kamila and Hall, Per and Cox, Angela and Cross, Simon and Swerdlow, Anthony and Schoemaker, Minouk J. and Dunning, Alison M. and Kaaks, Rudolf and Pharoah, Paul D. P. and Schmidt, Marjanka and Garcia-Closas, Montserrat and Easton, Douglas F. and Milne, Roger L. and Chang-Claude, Jenny},
	year = {2017},
	pmid = {28670784},
	pmcid = {PMC5601244},
	keywords = {Alcohol Drinking, Breast Cancer Association Consortium, Breast Neoplasms, CASP8 and FADD-Like Apoptosis Regulating Protein, Estrogen Receptor alpha, Female, Gene-Environment Interaction, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Risk Factors, Smoking, breast cancer, gene-environment, interaction, single nucleotide polymorphism},
	pages = {1830--1840},
}
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