Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project
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AuthorDierssen-Sotos, Trinidad; Palazuelos-Calderón, Camilo; Jiménez Moleón, José Juan; Aragonés, Nuria; Altzibar, Jone M.; Castaño-Vinyals, Gemma; Martín-Sanchez, Vicente; Gómez-Acebo, Inés; Guevara, Marcela; Tardón, Adonina; Pérez-Gómez, Beatriz; Amiano, Pilar; Moreno, Victor; Molina, Antonio J.; Alonso-Molero, Jéssica; Moreno-Iribas, Conchi; Kogevinas, Manolis; Pollán, Marina; Llorca, Javier
Breast cancerGenetic interactionsReproductive factors
Dierssen-Sotos, Trinidad; et al. Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project. BMC Cancer (2018) 18:280 [http://hdl.handle.net/10481/51253]
SponsorshipThis work was partially funded by the “Accion Transversal del Cancer”, approved by the Spanish Ministry Council on the 11th October 2007; The Instituto de Salud Carlos III-FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/ 00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032]; The Fundación Marqués de Valdecilla [API 10/09]; The ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)); The Junta de Castilla y León [LE22A10–2]; The Consejería de Salud of the Junta de Andalucía [2009-S0143]; The Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; The Recercaixa [2010ACUP 00310]; The Regional Government of the Basque Country; The Consejería de Sanidad de la Región de Murcia; The European Commission [grants FOOD-CT-2006-036224-HIWATE]; The Spanish Association Against Cancer (AECC) Scientific Foundation; The Catalan Government DURSI [grant 2014SGR647]; The Fundación Caja de Ahorros de Asturias; and the University of Oviedo.
Background: Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. Methods: One thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. Results: Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1–2 and > 2 deliveries were 0.48 (0.28–0.81) and 0.34 (0.19–0.59), and in C carriers they were 0.92 (0.42–1.98) and 0.71 (0.31–1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. Conclusions: The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect.