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Road traffic noise and breast cancer : DNA methylation in four core circadian genes

Thacher, Jesse D LU ; Snigireva, Anastasiia ; Dauter, Ulrike Maria ; Delaval, Mathilde N ; Oudin, Anna LU ; Mattisson, Kristoffer LU orcid ; Sørensen, Mette ; Borgquist, Signe LU ; Albin, Maria LU and Broberg, Karin LU orcid (2024) In Clinical Epigenetics 16(1).
Abstract

BACKGROUND: Transportation noise has been linked with breast cancer, but existing literature is conflicting. One proposed mechanism is that transportation noise disrupts sleep and the circadian rhythm. We investigated the relationships between road traffic noise, DNA methylation in circadian rhythm genes, and breast cancer. We selected 610 female participants (318 breast cancer cases and 292 controls) enrolled into the Malmö, Diet, and Cancer cohort. DNA methylation of CpGs (N = 29) in regulatory regions of circadian rhythm genes (CRY1, BMAL1, CLOCK, and PER1) was assessed by pyrosequencing of DNA from lymphocytes collected at enrollment. To assess associations between modeled 5-year mean residential road traffic noise and... (More)

BACKGROUND: Transportation noise has been linked with breast cancer, but existing literature is conflicting. One proposed mechanism is that transportation noise disrupts sleep and the circadian rhythm. We investigated the relationships between road traffic noise, DNA methylation in circadian rhythm genes, and breast cancer. We selected 610 female participants (318 breast cancer cases and 292 controls) enrolled into the Malmö, Diet, and Cancer cohort. DNA methylation of CpGs (N = 29) in regulatory regions of circadian rhythm genes (CRY1, BMAL1, CLOCK, and PER1) was assessed by pyrosequencing of DNA from lymphocytes collected at enrollment. To assess associations between modeled 5-year mean residential road traffic noise and differentially methylated CpG positions, we used linear regression models adjusting for potential confounders, including sociodemographics, shiftwork, and air pollution. Linear mixed effects models were used to evaluate road traffic noise and differentially methylated regions. Unconditional logistic regression was used to investigate CpG methylation and breast cancer.

RESULTS: We found that higher mean road traffic noise was associated with lower DNA methylation of three CRY1 CpGs (CpG1, CpG2, and CpG12) and three BMAL1 CpGs (CpG2, CpG6, and CpG7). Road traffic noise was also associated with differential methylation of CRY1 and BMAL1 promoters. In CRY1 CpG2 and CpG5 and in CLOCK CpG1, increasing levels of methylation tended to be associated with lower odds of breast cancer, with odds ratios (OR) of 0.88 (95% confidence interval (CI) 0.76-1.02), 0.84 (95% CI 0.74-0.96), and 0.80 (95% CI 0.68-0.94), respectively.

CONCLUSIONS: In summary, our data suggest that DNA hypomethylation in CRY1 and BMAL1 could be part of a causal chain from road traffic noise to breast cancer. This is consistent with the hypothesis that disruption of the circadian rhythm, e.g., from road traffic noise exposure, increases the risk of breast cancer. Since no prior studies have explored this association, it is essential to replicate our results.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, DNA Methylation/genetics, Female, Breast Neoplasms/genetics, Middle Aged, CpG Islands/genetics, Noise, Transportation/adverse effects, Cryptochromes/genetics, ARNTL Transcription Factors/genetics, Circadian Rhythm/genetics, Aged, Case-Control Studies, CLOCK Proteins/genetics, Period Circadian Proteins/genetics
in
Clinical Epigenetics
volume
16
issue
1
article number
168
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85210146374
  • pmid:39587706
ISSN
1868-7075
DOI
10.1186/s13148-024-01774-z
language
English
LU publication?
yes
additional info
© 2024. The Author(s).
id
c326116b-7e4e-4674-b5e8-66f93c1504b7
date added to LUP
2024-12-04 11:35:30
date last changed
2025-01-30 08:57:30
@article{c326116b-7e4e-4674-b5e8-66f93c1504b7,
  abstract     = {{<p>BACKGROUND: Transportation noise has been linked with breast cancer, but existing literature is conflicting. One proposed mechanism is that transportation noise disrupts sleep and the circadian rhythm. We investigated the relationships between road traffic noise, DNA methylation in circadian rhythm genes, and breast cancer. We selected 610 female participants (318 breast cancer cases and 292 controls) enrolled into the Malmö, Diet, and Cancer cohort. DNA methylation of CpGs (N = 29) in regulatory regions of circadian rhythm genes (CRY1, BMAL1, CLOCK, and PER1) was assessed by pyrosequencing of DNA from lymphocytes collected at enrollment. To assess associations between modeled 5-year mean residential road traffic noise and differentially methylated CpG positions, we used linear regression models adjusting for potential confounders, including sociodemographics, shiftwork, and air pollution. Linear mixed effects models were used to evaluate road traffic noise and differentially methylated regions. Unconditional logistic regression was used to investigate CpG methylation and breast cancer.</p><p>RESULTS: We found that higher mean road traffic noise was associated with lower DNA methylation of three CRY1 CpGs (CpG1, CpG2, and CpG12) and three BMAL1 CpGs (CpG2, CpG6, and CpG7). Road traffic noise was also associated with differential methylation of CRY1 and BMAL1 promoters. In CRY1 CpG2 and CpG5 and in CLOCK CpG1, increasing levels of methylation tended to be associated with lower odds of breast cancer, with odds ratios (OR) of 0.88 (95% confidence interval (CI) 0.76-1.02), 0.84 (95% CI 0.74-0.96), and 0.80 (95% CI 0.68-0.94), respectively.</p><p>CONCLUSIONS: In summary, our data suggest that DNA hypomethylation in CRY1 and BMAL1 could be part of a causal chain from road traffic noise to breast cancer. This is consistent with the hypothesis that disruption of the circadian rhythm, e.g., from road traffic noise exposure, increases the risk of breast cancer. Since no prior studies have explored this association, it is essential to replicate our results.</p>}},
  author       = {{Thacher, Jesse D and Snigireva, Anastasiia and Dauter, Ulrike Maria and Delaval, Mathilde N and Oudin, Anna and Mattisson, Kristoffer and Sørensen, Mette and Borgquist, Signe and Albin, Maria and Broberg, Karin}},
  issn         = {{1868-7075}},
  keywords     = {{Humans; DNA Methylation/genetics; Female; Breast Neoplasms/genetics; Middle Aged; CpG Islands/genetics; Noise, Transportation/adverse effects; Cryptochromes/genetics; ARNTL Transcription Factors/genetics; Circadian Rhythm/genetics; Aged; Case-Control Studies; CLOCK Proteins/genetics; Period Circadian Proteins/genetics}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Clinical Epigenetics}},
  title        = {{Road traffic noise and breast cancer : DNA methylation in four core circadian genes}},
  url          = {{http://dx.doi.org/10.1186/s13148-024-01774-z}},
  doi          = {{10.1186/s13148-024-01774-z}},
  volume       = {{16}},
  year         = {{2024}},
}