PLoS ONE (Jan 2019)

Genetic variants in genes related to inflammation, apoptosis and autophagy in breast cancer risk.

  • Johanna M Schuetz,
  • Anne Grundy,
  • Derrick G Lee,
  • Agnes S Lai,
  • Lindsay C Kobayashi,
  • Harriet Richardson,
  • Jirong Long,
  • Wei Zheng,
  • Kristan J Aronson,
  • John J Spinelli,
  • Angela R Brooks-Wilson

DOI
https://doi.org/10.1371/journal.pone.0209010
Journal volume & issue
Vol. 14, no. 1
p. e0209010

Abstract

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BackgroundInflammation contributes to breast cancer development through its effects on cell damage. This damage is usually dealt with by key genes involved in apoptosis and autophagy pathways.MethodsWe tested 206 single nucleotide polymorphisms (SNPs) in 54 genes related to inflammation, apoptosis and autophagy in a population-based breast cancer study of women of European (658 cases and 795 controls) and East Asian (262 cases and 127 controls) descent. Logistic regression was used to estimate odds ratios for breast cancer risk, and case-only analysis to compare breast cancer subtypes (defined by ER/PR/HER2 status), with adjustment for confounders. We assessed statistical interactions between the SNPs and lifestyle factors (smoking status, physical activity and body mass index).Results and conclusionAlthough no SNP was associated with breast cancer risk among women of European descent, we found evidence for an association among East Asians for rs1800925 (IL-13) and breast cancer risk (OR = 2.08; 95% CI: 1.32-3.28; p = 0.000779), which remained statistically significant after multiple testing correction (padj = 0.0350). This association was replicated in a meta-analysis of 4305 cases and 4194 controls in the Shanghai Breast Cancer Genetics Study (OR 1.12, 95% CI: 1.03-1.21, p = 0.011). Further, we found evidence of an interaction between rs7874234 (TSC1) and physical activity among women of East Asian descent.