Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors

Catherine L. Callahan, Matthew R. Bonner, Jing Nie, Daikwon Han, Youjin Wang, Menghua Tao, Peter G. Shields, Catalin Marian, Kevin H. Eng, Maurizio Trevisan, Jan Beyea, Jo L. Freudenheim

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3 Citations (Scopus)

Abstract

Background We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. Methods We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. Results Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23–0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03–3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05–5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26–0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). Conclusions We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

Original languageEnglish
Pages (from-to)418-424
Number of pages7
JournalEnvironmental Research
Volume161
DOIs
StatePublished - 1 Feb 2018

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Methylation
Air Pollution
methylation
Tumor Suppressor Genes
Air pollution
tumor
ambient air
Tumors
atmospheric pollution
Genes
Breast Neoplasms
traffic emission
gene
Odds Ratio
Menarche
Birth Order
Polycyclic Aromatic Hydrocarbons
DNA Methylation
PAH
DNA

Cite this

Callahan, Catherine L. ; Bonner, Matthew R. ; Nie, Jing ; Han, Daikwon ; Wang, Youjin ; Tao, Menghua ; Shields, Peter G. ; Marian, Catalin ; Eng, Kevin H. ; Trevisan, Maurizio ; Beyea, Jan ; Freudenheim, Jo L. / Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors. In: Environmental Research. 2018 ; Vol. 161. pp. 418-424.
@article{cc3f675142464b7ca888b4badb688bb1,
title = "Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors",
abstract = "Background We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. Methods We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. Results Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95{\%} CI: 0.23–0.99) and higher methylation of SYK (OR = 1.86, 95{\%} CI: 1.03–3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95{\%} CI: 1.05–5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95{\%} CI: 0.26–0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). Conclusions We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.",
author = "Callahan, {Catherine L.} and Bonner, {Matthew R.} and Jing Nie and Daikwon Han and Youjin Wang and Menghua Tao and Shields, {Peter G.} and Catalin Marian and Eng, {Kevin H.} and Maurizio Trevisan and Jan Beyea and Freudenheim, {Jo L.}",
year = "2018",
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doi = "10.1016/j.envres.2017.11.040",
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Callahan, CL, Bonner, MR, Nie, J, Han, D, Wang, Y, Tao, M, Shields, PG, Marian, C, Eng, KH, Trevisan, M, Beyea, J & Freudenheim, JL 2018, 'Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors', Environmental Research, vol. 161, pp. 418-424. https://doi.org/10.1016/j.envres.2017.11.040

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors. / Callahan, Catherine L.; Bonner, Matthew R.; Nie, Jing; Han, Daikwon; Wang, Youjin; Tao, Menghua; Shields, Peter G.; Marian, Catalin; Eng, Kevin H.; Trevisan, Maurizio; Beyea, Jan; Freudenheim, Jo L.

In: Environmental Research, Vol. 161, 01.02.2018, p. 418-424.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors

AU - Callahan, Catherine L.

AU - Bonner, Matthew R.

AU - Nie, Jing

AU - Han, Daikwon

AU - Wang, Youjin

AU - Tao, Menghua

AU - Shields, Peter G.

AU - Marian, Catalin

AU - Eng, Kevin H.

AU - Trevisan, Maurizio

AU - Beyea, Jan

AU - Freudenheim, Jo L.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Background We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. Methods We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. Results Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23–0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03–3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05–5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26–0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). Conclusions We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

AB - Background We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. Methods We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. Results Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23–0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03–3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05–5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26–0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). Conclusions We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

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DO - 10.1016/j.envres.2017.11.040

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JO - Environmental Research

JF - Environmental Research

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