Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project

Dierssen Sotos, Trinidad; Palazuelos, Camilo; Jiménez-Moleón, José Juan; Aragonés, Núria; Altzibar, Jone Miren; Castaño Vinyals, Gemma; Martín Sánchez, Vicente; Gómez-Acebo, Inés; Guevara, Marcela; Tardón, Adonina; Pérez-Gómez, Beatriz; Amiano, Pilar; Moreno, Víctor; Molina, Antonio J.; Alonso Molero, Jessica; Moreno-Iribas, Conchi; Kogevinas, Manolis; Pollán, Marina; Llorca, Javier

doi:http://dx.doi.org/10.1186/s12885-018-4182-3

Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project

Citation

Dierssen-Sotos T, Palazuelos-Calderón C, Jiménez-Moleón JJ, Aragonés N, Altzibar JM, Castaño-Vinyals G et al. Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project. BMC Cancer. 2018 Mar 12;18(1):280. DOI: 10.1186/s12885-018-4182-3

Abstract

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.