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Genome-wide Association Analysis of Proinflammatory Cytokines and Gene-lifestyle Interaction for Invasive Breast
Su Yon Jung1, Peter A Scott2, Jeanette C Papp3
1Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, California. sjung@sonnet.ucla.edu.
Cancer Prevention Research (Philadelphia, Pa.)
|September 15, 2020
Summary
This study identified genetic markers for inflammation that interact with obesity, increasing breast cancer risk in postmenopausal women. These findings suggest targeted interventions for women with specific genetic predispositions to reduce cancer risk.
Area of Science:
- Genetics
- Oncology
- Epidemiology
Background:
- Invasive breast cancer risk is influenced by immune pathways, but molecular genetic links and interactions with lifestyle remain unclear.
- Postmenopausal women are particularly susceptible to inflammation and obesity, increasing their breast cancer risk.
- Understanding gene-environment interactions is crucial for developing targeted prevention strategies.
Purpose of the Study:
- To investigate genome-wide gene-environment interactions (GxE) for proinflammatory cytokines (IL6, CRP) and their association with breast cancer risk.
- To identify single-nucleotide polymorphisms (SNPs) associated with inflammation and their interaction with obesity and lifestyle factors.
- To explore the role of these genetic variations in breast carcinogenesis.
Main Methods:
- Genome-wide association (GWA) analysis of 21,784,812 common autosomal SNPs in 16,088 postmenopausal women from the Women's Health Initiative.
- GWA gene-environment interaction analysis for IL6 and CRP, considering obesity status and lifestyle factors (diet, exercise).
- Association testing of identified SNPs with invasive breast cancer risk.
Main Results:
- 88 GWA SNPs in 10 loci were associated with IL6 and CRP, with novel markers identified.
- 27 SNPs in *HNF1A-AS1*, *HNF1A*, and *C1q2orf43* were significantly associated with increased breast cancer risk.
- Significant interactions were observed between inflammatory biomarkers, obesity factors, and breast cancer risk.
Conclusions:
- Genetic variations in inflammatory pathways, particularly those related to CRP and IL6, interact with obesity to influence breast cancer risk.
- Specific SNPs identified may serve as biomarkers for identifying high-risk individuals.
- Findings support the development of targeted interventions for women with inflammatory-risk genotypes to mitigate breast cancer risk.
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