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PLoS One. 2019 Jan 2;14(1):e0209010. doi: 10.1371/journal.pone.0209010. eCollection 2019.

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

Author information

1
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
2
CRCHUM (Centre de recherche du Centre hospitalier de l'Université de Montréal), Montreal, QC, Canada.
3
Department of Social and Preventive Medicine, Université de Montréal, Montreal, QC, Canada.
4
Department of Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada.
5
Department of Mathematics, Statistics, and Computer Science, St. Francis Xavier University, Antigonish, NS, Canada.
6
Harvard Center for Population and Development Studies, Harvard T. H. Chan School of Public Health, Cambridge, MA, United States of America.
7
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States of America.
8
Department of Public Health Sciences, Queen's University, Kingston, ON, Canada.
9
Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Kingston, ON, Canada.
10
Vanderbilt Epidemiology Centre, Vanderbilt University Medical Center, Nashville, TN, United States of America.
11
School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
12
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.

Abstract

BACKGROUND:

Inflammation 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.

METHODS:

We 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 CONCLUSION:

Although 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.

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