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Interplay between AHR genotypes, lifestyle factors and adjuvant breast cancer treatments significantly impacts clinical outcome in a population-based cohort

Augustinsson, Annelie LU ; Godina, Christopher LU orcid ; Nilsson, Linn LU ; Gonçalves de Oliveira, Kelin LU ; Isaksson, Karolin LU and Jernström, Helena LU (2025) In British journal of Cancer Reports 3.
Abstract
Background
The purpose was to evaluate the prognostic impact of aryl hydrocarbon receptor (AHR) genotypes in relation to lifestyle and adjuvant treatments in breast cancer.

Methods
AHR genotyping was performed on genomic DNA from 1701 patients included 2002–2016 in Lund, Sweden, and followed for up to 15 years. Eight AHR polymorphisms and eight haplotypes were analysed using survival and interaction analyses in relation to prognosis.

Results
Homozygosity for major allele frequencies was 42.1%–88.5%. AHR genotypes linked to lower AHR expression conferred differential prognosis combined with smoking, alcohol, antioxidant supplements, chemotherapy or endocrine therapy, with interactions between exposures and... (More)
Background
The purpose was to evaluate the prognostic impact of aryl hydrocarbon receptor (AHR) genotypes in relation to lifestyle and adjuvant treatments in breast cancer.

Methods
AHR genotyping was performed on genomic DNA from 1701 patients included 2002–2016 in Lund, Sweden, and followed for up to 15 years. Eight AHR polymorphisms and eight haplotypes were analysed using survival and interaction analyses in relation to prognosis.

Results
Homozygosity for major allele frequencies was 42.1%–88.5%. AHR genotypes linked to lower AHR expression conferred differential prognosis combined with smoking, alcohol, antioxidant supplements, chemotherapy or endocrine therapy, with interactions between exposures and genotypes. Preoperative antioxidants combined with minor alleles of AHR_6 or AHR_9 conferred three-fold risks for breast cancer events, not seen in other patients (Pinteractions ≤ 0.016). Interactions between the CGATTAGC haplotype and chemotherapy revealed five-fold risks for breast cancer events or death compared to other haplotypes or no chemotherapy (Pinteractions ≤ 0.010). AHR genotypes were not prognostic in radiation therapy-treated patients.

Conclusions
The prognostic impact of AHR genotypes depended on lifestyle and treatments, possibly due to the role of AhR as master regulator of metabolism, hypoxia, DNA repair and immune response. If confirmed, these findings may contribute to more personalised lifestyle recommendations and treatment. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British journal of Cancer Reports
volume
3
article number
51
publisher
Springer Nature
external identifiers
  • pmid:40646277
ISSN
2731-9377
DOI
10.1038/s44276-025-00167-w
language
English
LU publication?
yes
id
168ce223-15de-420e-b15e-363147253d60
date added to LUP
2025-09-09 10:56:55
date last changed
2025-09-10 03:26:55
@article{168ce223-15de-420e-b15e-363147253d60,
  abstract     = {{Background<br/>The purpose was to evaluate the prognostic impact of aryl hydrocarbon receptor (AHR) genotypes in relation to lifestyle and adjuvant treatments in breast cancer.<br/><br/>Methods<br/>AHR genotyping was performed on genomic DNA from 1701 patients included 2002–2016 in Lund, Sweden, and followed for up to 15 years. Eight AHR polymorphisms and eight haplotypes were analysed using survival and interaction analyses in relation to prognosis.<br/><br/>Results<br/>Homozygosity for major allele frequencies was 42.1%–88.5%. AHR genotypes linked to lower AHR expression conferred differential prognosis combined with smoking, alcohol, antioxidant supplements, chemotherapy or endocrine therapy, with interactions between exposures and genotypes. Preoperative antioxidants combined with minor alleles of AHR_6 or AHR_9 conferred three-fold risks for breast cancer events, not seen in other patients (Pinteractions ≤ 0.016). Interactions between the CGATTAGC haplotype and chemotherapy revealed five-fold risks for breast cancer events or death compared to other haplotypes or no chemotherapy (Pinteractions ≤ 0.010). AHR genotypes were not prognostic in radiation therapy-treated patients.<br/><br/>Conclusions<br/>The prognostic impact of AHR genotypes depended on lifestyle and treatments, possibly due to the role of AhR as master regulator of metabolism, hypoxia, DNA repair and immune response. If confirmed, these findings may contribute to more personalised lifestyle recommendations and treatment.}},
  author       = {{Augustinsson, Annelie and Godina, Christopher and Nilsson, Linn and Gonçalves de Oliveira, Kelin and Isaksson, Karolin and Jernström, Helena}},
  issn         = {{2731-9377}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{Springer Nature}},
  series       = {{British journal of Cancer Reports}},
  title        = {{Interplay between AHR genotypes, lifestyle factors and adjuvant breast cancer treatments significantly impacts clinical outcome in a population-based cohort}},
  url          = {{http://dx.doi.org/10.1038/s44276-025-00167-w}},
  doi          = {{10.1038/s44276-025-00167-w}},
  volume       = {{3}},
  year         = {{2025}},
}