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.

Keywords: Breast cancer; Genetic interactions; Reproductive factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6
  • Adult
  • Aged
  • Alleles
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Breast Neoplasms / complications
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Hormones / genetics
  • Humans
  • Metabolic Networks and Pathways
  • Middle Aged
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Parity / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Reproduction / genetics*
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Risk Factors
  • Spain
  • Surveys and Questionnaires
  • src-Family Kinases / genetics

Substances

  • ATF6B protein, human
  • Activating Transcription Factor 6
  • Basic-Leucine Zipper Transcription Factors
  • CREB3L1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Hormones
  • Nerve Tissue Proteins
  • src-Family Kinases
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa