Association between Urinary Phenols and Parabens as well as Breast Cancer
Abstract
Background: Phenols and parabens have been associated with various adverse health outcomes. However, their relationship with breast cancer remains inconsistent, and the combined effect is still unknown. This study aimed to examine the association between mixed phenols and parabens and breast cancer among female adults.
Method: Participants for this study were obtained from six cycles of the National Health and Nutrition Examination Survey (NHANES). The weighted logistic regression model was employed to investigate the relationship between individual chemicals and breast cancer. Furthermore, the weighted quantile sum (WQS) regression was used to assess the joint effects of phenols and parabens on breast cancer.
Results: The study included 4993 participants, with 154 women diagnosed with breast cancer. After adjusting for all potential covariates, triclosan (TCS) showed a positive association with breast cancer (OR for Q3 = 2.12, 95% CI: 1.23-3.65), while propylparaben (PrPB) exhibited a negative association with breast cancer (OR for Q4 = 0.48, 95% CI: 0.23-0.98). The WQS regression mode found no significant difference between mixed chemicals and breast cancer (OR for positive model = 1.09, 95% CI: 0.65-1.84 and OR for negative model = 0.95, 95% CI: 0.57-1.58).
Conclusion: Exposure to phenols and parabens has distinct effects on breast cancer risk. High-quality research is essential to obtain conclusions that are more reliable and uncover potential underlying mechanisms.
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8. Filippini T, Torres D, Lopes C, et al (2020). Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies. Environ Int, 142:105879.
9. Romieu I, Scoccianti C, Chajès V, et al (2015). Alcohol intake and breast cancer in the European prospective investiga-tion into cancer and nutrition. Int J Can-cer, 137 (8):1921-30.
10. Gaudet MM, Gapstur SM, Sun J, Diver WR, Hannan LM, Thun MJ (2013). Active smoking and breast cancer risk: original cohort data and meta-analysis. J Natl Cancer Inst, 105 (8):515-25.
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13. Tao J, Bai C, Chen Y, et al (2020). Envi-ronmental relevant concentrations of benzophenone-3 induced developmen-tal neurotoxicity in zebrafish. Sci Total Environ, 721:137686.
14. Dann AB, Hontela A (2011). Triclosan: en-vironmental exposure, toxicity and mechanisms of action. J Appl Toxicol, 31 (4):285-311.
15. Jiménez-Díaz I, Artacho-Cordón F, Vela-Soria F, et al (2016). Urinary levels of bi-sphenol A, benzophenones and para-bens in Tunisian women: A pilot study. Sci Total Environ, 562:81-88.
16. Błędzka D, Gromadzińska J, Wąsowicz W (2014). Parabens. From environmental studies to human health. Environ Int, 67:27-42.
17. Pycke BF, Geer LA, Dalloul M, Abulafia O, Halden RU (2015). Maternal and fetal exposure to parabens in a multiethnic urban U.S. population. Environ Int, 84:193-200.
18. Zhao Y, Liu Y, Chen Y, et al (2021). Expo-sure to parabens and associations with oxidative stress in adults from South China. Sci Total Environ, 774:144917.
19. Liang J, Liu QS, Ren Z, et al (2023). Study-ing paraben-induced estrogen receptor- and steroid hormone-related endocrine disruption effects via multi-level ap-proaches. Sci Total Environ, 869:161793.
20. Fourkala EO, Zaikin A, Burnell M, et al (2012). Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women. Endocr Relat Cancer, 19 (2):137-47.
21. Mousa NA, Marino N, Simões BM (2023). Editorial: Sex steroid hormones: effects on breast cancer risk and etiology. Front Endocrinol (Lausanne), 14:1198770.
22. Hu P, Pan C, Su W, et al (2022). Associations between exposure to a mixture of phe-nols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016. Sci Total En-viron, 822:153548.
23. Xu X, Dong F, Yang Y, Wang Y, Wang R, Shen X (2015). Sex-specific effects of long-term exposure to bisphenol-A on anxiety- and depression-like behaviors in adult mice. Chemosphere, 120:258-66.
24. Guo M, Zhu C (2023). Associations between exposure to a mixture of phenols and sex steroid hormones among pre- and postmenopausal women: evidence from NHANES 2015-2016. Environ Sci Pollut Res Int, 30 (19):57103-57113.
25. He H, Deng Y, Wan H, et al (2022). Urinary bisphenol A and its interaction with CYP17A1 rs743572 are associated with breast cancer risk. Chemosphere, 286 (Pt 3):131880.
26. Parada H, Jr., Gammon MD, Ettore HL, et al (2019). Urinary concentrations of en-vironmental phenols and their associa-tions with breast cancer incidence and mortality following breast cancer. Envi-ron Int, 130:104890.
27. Parada H, Jr., Sahrai L, Wolff MS, et al (2022). Urinary parabens and breast cancer risk: Modification by LINE-1 and LUMA global DNA methylation, and associations with breast cancer de-fined by tumor promoter methylation status. Mol Carcinog, 61 (11):1002-1015.
28. Salamanca-Fernández E, Rodríguez-Barranco M, Amiano P, et al (2021). Bi-sphenol-A exposure and risk of breast and prostate cancer in the Spanish Eu-ropean Prospective Investigation into Cancer and Nutrition study. Environ Health, 20 (1):88.
29. Wu AH, Franke AA, Wilkens LR, et al (2021). Risk of breast cancer and predi-agnostic urinary excretion of bisphenol A, triclosan and parabens: The Multi-ethnic Cohort Study. Int J Cancer, 149 (7):1426-1434.
30. Iranpour S, Sabour S (2019). Inverse associ-ation between caffeine intake and de-pressive symptoms in US adults: data from National Health and Nutrition Examination Survey (NHANES) 2005-2006. Psychiatry Res, 271:732-739.
31. Zhou X, Ye X, Calafat AM (2012). Automat-ed on-line column-switching HPLC-MS/MS method for the quantification of triclocarban and its oxidative metab-olites in human urine and serum. J Chromatogr B Analyt Technol Biomed Life Sci, 881-882:27-33.
32. Ashley DL, Smith MM, Silva LK, Yoo YM, De Jesús VR, Blount BC (2020). Factors Associated with Exposure to Trihalome-thanes, NHANES 2001-2012. Environ Sci Technol, 54 (2):1066-1074.
33. Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL (2005). Uri-nary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. En-viron Health Perspect, 113 (2):192-200.
34. Cai X, Ning C, Fan L, et al (2023). Triclosan is associated with breast cancer via oxi-dative stress and relative telomere length. Front Public Health, 11:1163965.
35. Farasani A, Darbre PD (2021). Long-term exposure to triclosan increases migra-tion and invasion of human breast epi-thelial cells in vitro. J Appl Toxicol, 41 (7):1115-1126.
36. Lee GA, Choi KC, Hwang KA (2018). Treatment with Phytoestrogens Re-versed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Can-cer Cells. Biomol Ther (Seoul), 26 (5):503-511.
37. Chen J, Xie P, Wu P, Lin Z, He Y, Cai Z (2023). Spatial Metabolomics and Lip-idomics Reveal the Mechanisms of the Enhanced Growth of Breast Cancer Cell Spheroids Exposed to Triclosan. Environ Sci Technol, 57 (29):10542-10553.
38. Liu S, Wang P, Wang C, et al (2023). Dis-parate toxicity mechanisms of parabens with different alkyl chain length in freshwater biofilms: Ecological hazards associated with antibiotic resistome. Sci Total Environ, 881:163168.
39. Zhang Y, Dong T, Hu W, et al (2019). Asso-ciation between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statis-tical models. Environ Int, 123:325-336.
40. Czarnota J, Gennings C, Colt JS, et al (2015). Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study. Environ Health Perspect, 123 (10):965-70.
2. Sung H, Ferlay J, Siegel RL, et al (2021). Global Cancer Statistics 2020: GLO-BOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71 (3):209-249.
3. Lukong KE, Ogunbolude Y, Kamdem JP (2017). Breast cancer in Africa: preva-lence, treatment options, herbal medi-cines, and socioeconomic determinants. Breast Cancer Res Treat, 166 (2):351-365.
4. Li T, Mello-Thoms C, Brennan PC (2016). Descriptive epidemiology of breast cancer in China: incidence, mortality, survival and prevalence. Breast Cancer Res Treat, 159 (3):395-406.
5. Rodgers KM, Udesky JO, Rudel RA, Brody JG (2018). Environmental chemicals and breast cancer: An updated review of ep-idemiological literature informed by bi-ological mechanisms. Environ Res, 160:152-182.
6. Kerr J, Anderson C, Lippman SM (2017). Physical activity, sedentary behaviour, diet, and cancer: an update and emerg-ing new evidence. Lancet Oncol, 18 (8):e457-e471.
7. Ripperger T, Gadzicki D, Meindl A, Schle-gelberger B (2009). Breast cancer suscep-tibility: current knowledge and implica-tions for genetic counselling. Eur J Hum Genet, 17 (6):722-31.
8. Filippini T, Torres D, Lopes C, et al (2020). Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies. Environ Int, 142:105879.
9. Romieu I, Scoccianti C, Chajès V, et al (2015). Alcohol intake and breast cancer in the European prospective investiga-tion into cancer and nutrition. Int J Can-cer, 137 (8):1921-30.
10. Gaudet MM, Gapstur SM, Sun J, Diver WR, Hannan LM, Thun MJ (2013). Active smoking and breast cancer risk: original cohort data and meta-analysis. J Natl Cancer Inst, 105 (8):515-25.
11. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, et al (2009). Endocrine-disrupting chemicals: an Endocrine So-ciety scientific statement. Endocr Rev, 30 (4):293-342.
12. Bonefeld-Jørgensen EC, Long M, Hofmeis-ter MV, Vinggaard AM (2007). Endo-crine-disrupting potential of bisphenol A, bisphenol A dimethacrylate, 4-n-nonylphenol, and 4-n-octylphenol in vitro: new data and a brief review. Envi-ron Health Perspect, 115 Suppl 1 (Suppl 1):69-76.
13. Tao J, Bai C, Chen Y, et al (2020). Envi-ronmental relevant concentrations of benzophenone-3 induced developmen-tal neurotoxicity in zebrafish. Sci Total Environ, 721:137686.
14. Dann AB, Hontela A (2011). Triclosan: en-vironmental exposure, toxicity and mechanisms of action. J Appl Toxicol, 31 (4):285-311.
15. Jiménez-Díaz I, Artacho-Cordón F, Vela-Soria F, et al (2016). Urinary levels of bi-sphenol A, benzophenones and para-bens in Tunisian women: A pilot study. Sci Total Environ, 562:81-88.
16. Błędzka D, Gromadzińska J, Wąsowicz W (2014). Parabens. From environmental studies to human health. Environ Int, 67:27-42.
17. Pycke BF, Geer LA, Dalloul M, Abulafia O, Halden RU (2015). Maternal and fetal exposure to parabens in a multiethnic urban U.S. population. Environ Int, 84:193-200.
18. Zhao Y, Liu Y, Chen Y, et al (2021). Expo-sure to parabens and associations with oxidative stress in adults from South China. Sci Total Environ, 774:144917.
19. Liang J, Liu QS, Ren Z, et al (2023). Study-ing paraben-induced estrogen receptor- and steroid hormone-related endocrine disruption effects via multi-level ap-proaches. Sci Total Environ, 869:161793.
20. Fourkala EO, Zaikin A, Burnell M, et al (2012). Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women. Endocr Relat Cancer, 19 (2):137-47.
21. Mousa NA, Marino N, Simões BM (2023). Editorial: Sex steroid hormones: effects on breast cancer risk and etiology. Front Endocrinol (Lausanne), 14:1198770.
22. Hu P, Pan C, Su W, et al (2022). Associations between exposure to a mixture of phe-nols, parabens, and phthalates and sex steroid hormones in children 6-19 years from NHANES, 2013-2016. Sci Total En-viron, 822:153548.
23. Xu X, Dong F, Yang Y, Wang Y, Wang R, Shen X (2015). Sex-specific effects of long-term exposure to bisphenol-A on anxiety- and depression-like behaviors in adult mice. Chemosphere, 120:258-66.
24. Guo M, Zhu C (2023). Associations between exposure to a mixture of phenols and sex steroid hormones among pre- and postmenopausal women: evidence from NHANES 2015-2016. Environ Sci Pollut Res Int, 30 (19):57103-57113.
25. He H, Deng Y, Wan H, et al (2022). Urinary bisphenol A and its interaction with CYP17A1 rs743572 are associated with breast cancer risk. Chemosphere, 286 (Pt 3):131880.
26. Parada H, Jr., Gammon MD, Ettore HL, et al (2019). Urinary concentrations of en-vironmental phenols and their associa-tions with breast cancer incidence and mortality following breast cancer. Envi-ron Int, 130:104890.
27. Parada H, Jr., Sahrai L, Wolff MS, et al (2022). Urinary parabens and breast cancer risk: Modification by LINE-1 and LUMA global DNA methylation, and associations with breast cancer de-fined by tumor promoter methylation status. Mol Carcinog, 61 (11):1002-1015.
28. Salamanca-Fernández E, Rodríguez-Barranco M, Amiano P, et al (2021). Bi-sphenol-A exposure and risk of breast and prostate cancer in the Spanish Eu-ropean Prospective Investigation into Cancer and Nutrition study. Environ Health, 20 (1):88.
29. Wu AH, Franke AA, Wilkens LR, et al (2021). Risk of breast cancer and predi-agnostic urinary excretion of bisphenol A, triclosan and parabens: The Multi-ethnic Cohort Study. Int J Cancer, 149 (7):1426-1434.
30. Iranpour S, Sabour S (2019). Inverse associ-ation between caffeine intake and de-pressive symptoms in US adults: data from National Health and Nutrition Examination Survey (NHANES) 2005-2006. Psychiatry Res, 271:732-739.
31. Zhou X, Ye X, Calafat AM (2012). Automat-ed on-line column-switching HPLC-MS/MS method for the quantification of triclocarban and its oxidative metab-olites in human urine and serum. J Chromatogr B Analyt Technol Biomed Life Sci, 881-882:27-33.
32. Ashley DL, Smith MM, Silva LK, Yoo YM, De Jesús VR, Blount BC (2020). Factors Associated with Exposure to Trihalome-thanes, NHANES 2001-2012. Environ Sci Technol, 54 (2):1066-1074.
33. Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL (2005). Uri-nary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. En-viron Health Perspect, 113 (2):192-200.
34. Cai X, Ning C, Fan L, et al (2023). Triclosan is associated with breast cancer via oxi-dative stress and relative telomere length. Front Public Health, 11:1163965.
35. Farasani A, Darbre PD (2021). Long-term exposure to triclosan increases migra-tion and invasion of human breast epi-thelial cells in vitro. J Appl Toxicol, 41 (7):1115-1126.
36. Lee GA, Choi KC, Hwang KA (2018). Treatment with Phytoestrogens Re-versed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Can-cer Cells. Biomol Ther (Seoul), 26 (5):503-511.
37. Chen J, Xie P, Wu P, Lin Z, He Y, Cai Z (2023). Spatial Metabolomics and Lip-idomics Reveal the Mechanisms of the Enhanced Growth of Breast Cancer Cell Spheroids Exposed to Triclosan. Environ Sci Technol, 57 (29):10542-10553.
38. Liu S, Wang P, Wang C, et al (2023). Dis-parate toxicity mechanisms of parabens with different alkyl chain length in freshwater biofilms: Ecological hazards associated with antibiotic resistome. Sci Total Environ, 881:163168.
39. Zhang Y, Dong T, Hu W, et al (2019). Asso-ciation between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statis-tical models. Environ Int, 123:325-336.
40. Czarnota J, Gennings C, Colt JS, et al (2015). Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study. Environ Health Perspect, 123 (10):965-70.
| Files | ||
| Issue | Vol 54 No 3 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Breast neoplasms Parabens Phenols Endocrine disruptors | ||
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How to Cite
1.
Wu P. Association between Urinary Phenols and Parabens as well as Breast Cancer. Iran J Public Health. 2025;54(3):634-644.
