Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort

Abstract Persistent organic pollutants (POPs) are a group of organic chemical compounds. Contradictory results have emerged in epidemiological studies attempting to elucidate their relationship with breast cancer risk. This study explored the relationship between dietary exposures to multiple POPs a...

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Main Authors: Pauline Frenoy, Ismaïl Ahmed, Chloé Marques, Xuan Ren, Gianluca Severi, Vittorio Perduca, Francesca Romana Mancini
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85438-9
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author Pauline Frenoy
Ismaïl Ahmed
Chloé Marques
Xuan Ren
Gianluca Severi
Vittorio Perduca
Francesca Romana Mancini
author_facet Pauline Frenoy
Ismaïl Ahmed
Chloé Marques
Xuan Ren
Gianluca Severi
Vittorio Perduca
Francesca Romana Mancini
author_sort Pauline Frenoy
collection DOAJ
description Abstract Persistent organic pollutants (POPs) are a group of organic chemical compounds. Contradictory results have emerged in epidemiological studies attempting to elucidate their relationship with breast cancer risk. This study explored the relationship between dietary exposures to multiple POPs and ER-positive breast cancer risk in the French E3N cohort study, using three different approaches to handle multicollinearity among exposures. Intakes of 81 POPs were estimated using food consumption data from a validated semi-quantitative food frequency questionnaire and food contamination data. In the first approach, hierarchical clustering was performed to identify clusters of correlated POPs. For each cluster, the levels of POPs belonging to it were averaged. These average levels were then included in a Cox model to estimate their associations with ER-positive breast cancer occurrence. The second and third approaches applied in the present study were Principal component Cox regression (PCR-Cox) and partial least squares Cox regression (PLS-Cox) respectively, both being dimension-reduction methods (respectively unsupervised and supervised) coupled to a Cox model, used to identify principal components of POPs and to estimate their associations with ER-positive breast occurrence. All models were adjusted for potential confounders previously identified using a directed acyclic graph. The study included 66,722 women with a median follow-up of 20.3 years, during which 3,739 developed an incident ER-positive breast cancer. The variable clustering method did not identify any association between the averaged variables and ER-positive breast cancer risk. Five components were retained using both the PCR-Cox and PLS-Cox methods explaining 82% and 77% of the variance in the initial exposure matrix respectively. Among these components, none was significantly associated with the occurrence of ER-positive breast cancer. This study provides an illustrative example of the application of three distinct statistical methods in the context of highly correlated environmental exposures, discussing their potential relevance and limitations within this specific framework.
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spelling doaj-art-471a482ec0dc447ea8524c89cd8bffc12025-01-19T12:22:43ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85438-9Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohortPauline Frenoy0Ismaïl Ahmed1Chloé Marques2Xuan Ren3Gianluca Severi4Vittorio Perduca5Francesca Romana Mancini6Inserm, Gustave Roussy, Centre for Research in Epidemiology and Population Health (CESP), “Exposome, Heredity, Cancer, and Health” Team, Université Paris-Saclay, UVSQInserm, CESP, Université Paris-Saclay, UVSQInserm, Gustave Roussy, Centre for Research in Epidemiology and Population Health (CESP), “Exposome, Heredity, Cancer, and Health” Team, Université Paris-Saclay, UVSQInserm, Gustave Roussy, Centre for Research in Epidemiology and Population Health (CESP), “Exposome, Heredity, Cancer, and Health” Team, Université Paris-Saclay, UVSQInserm, Gustave Roussy, Centre for Research in Epidemiology and Population Health (CESP), “Exposome, Heredity, Cancer, and Health” Team, Université Paris-Saclay, UVSQInserm, Gustave Roussy, Centre for Research in Epidemiology and Population Health (CESP), “Exposome, Heredity, Cancer, and Health” Team, Université Paris-Saclay, UVSQInserm, Gustave Roussy, Centre for Research in Epidemiology and Population Health (CESP), “Exposome, Heredity, Cancer, and Health” Team, Université Paris-Saclay, UVSQAbstract Persistent organic pollutants (POPs) are a group of organic chemical compounds. Contradictory results have emerged in epidemiological studies attempting to elucidate their relationship with breast cancer risk. This study explored the relationship between dietary exposures to multiple POPs and ER-positive breast cancer risk in the French E3N cohort study, using three different approaches to handle multicollinearity among exposures. Intakes of 81 POPs were estimated using food consumption data from a validated semi-quantitative food frequency questionnaire and food contamination data. In the first approach, hierarchical clustering was performed to identify clusters of correlated POPs. For each cluster, the levels of POPs belonging to it were averaged. These average levels were then included in a Cox model to estimate their associations with ER-positive breast cancer occurrence. The second and third approaches applied in the present study were Principal component Cox regression (PCR-Cox) and partial least squares Cox regression (PLS-Cox) respectively, both being dimension-reduction methods (respectively unsupervised and supervised) coupled to a Cox model, used to identify principal components of POPs and to estimate their associations with ER-positive breast occurrence. All models were adjusted for potential confounders previously identified using a directed acyclic graph. The study included 66,722 women with a median follow-up of 20.3 years, during which 3,739 developed an incident ER-positive breast cancer. The variable clustering method did not identify any association between the averaged variables and ER-positive breast cancer risk. Five components were retained using both the PCR-Cox and PLS-Cox methods explaining 82% and 77% of the variance in the initial exposure matrix respectively. Among these components, none was significantly associated with the occurrence of ER-positive breast cancer. This study provides an illustrative example of the application of three distinct statistical methods in the context of highly correlated environmental exposures, discussing their potential relevance and limitations within this specific framework.https://doi.org/10.1038/s41598-025-85438-9Persistent organic pollutantsMulticollinearityBreast cancer
spellingShingle Pauline Frenoy
Ismaïl Ahmed
Chloé Marques
Xuan Ren
Gianluca Severi
Vittorio Perduca
Francesca Romana Mancini
Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort
Scientific Reports
Persistent organic pollutants
Multicollinearity
Breast cancer
title Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort
title_full Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort
title_fullStr Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort
title_full_unstemmed Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort
title_short Application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on ER-positive breast cancer risk in the French E3N cohort
title_sort application of three statistical approaches to explore effects of dietary intake of multiple persistent organic pollutants on er positive breast cancer risk in the french e3n cohort
topic Persistent organic pollutants
Multicollinearity
Breast cancer
url https://doi.org/10.1038/s41598-025-85438-9
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