Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction

Abstract Molecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the g...

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Autores principales:	Su Yon Jung, Jeanette C. Papp, Eric M. Sobel, Matteo Pellegrini, Herbert Yu, Zuo-Feng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/459391e7ee394ca4a0a469265249ce60
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spelling	oai:doaj.org-article:459391e7ee394ca4a0a469265249ce602021-12-02T14:01:21ZPro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction10.1038/s41598-020-80197-12045-2322https://doaj.org/article/459391e7ee394ca4a0a469265249ce602021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80197-1https://doaj.org/toc/2045-2322Abstract Molecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women’s Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene–lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.Su Yon JungJeanette C. PappEric M. SobelMatteo PellegriniHerbert YuZuo-Feng ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Su Yon Jung Jeanette C. Papp Eric M. Sobel Matteo Pellegrini Herbert Yu Zuo-Feng Zhang Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
description	Abstract Molecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women’s Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene–lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.
format	article
author	Su Yon Jung Jeanette C. Papp Eric M. Sobel Matteo Pellegrini Herbert Yu Zuo-Feng Zhang
author_facet	Su Yon Jung Jeanette C. Papp Eric M. Sobel Matteo Pellegrini Herbert Yu Zuo-Feng Zhang
author_sort	Su Yon Jung
title	Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
title_short	Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
title_full	Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
title_fullStr	Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
title_full_unstemmed	Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
title_sort	pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/459391e7ee394ca4a0a469265249ce60
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Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction

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