title: Exposure to polychlorinated biphenyls and prostate cancer: population-based prospective cohort and experimental studies.
abstract: Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.
authors.forename: Imran
authors.initials: I
authors.lastname: Ali
authors.forename: Bettina
authors.initials: B
authors.lastname: Julin
authors.affiliation: The National Food Agency, Uppsala SE 751 26, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Glynn
authors.forename: Johan
authors.initials: J
authors.lastname: Högberg
authors.forename: Marika
authors.initials: M
authors.lastname: Berglund
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro SE 701 82, Sweden.|Department of Urology, Örebro University Hospital, Örebro SE 701 85, Sweden.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Johansson
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro SE 701 82, Sweden.|Department of Urology, Örebro University Hospital, Örebro SE 701 85, Sweden.
authors.forename: Swen-Olof
authors.initials: SO
authors.lastname: Andersson
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro SE 701 82, Sweden.|Department of Urology, Örebro University Hospital, Örebro SE 701 85, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Andrén
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.forename: Alicja
authors.initials: A
authors.lastname: Wolk
authors.forename: Ulla
authors.initials: U
authors.lastname: Stenius
authors.forename: Agneta
authors.initials: A
authors.lastname: Åkesson
mesh_terms: D000368:Aged; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004032:Diet / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D013548:Sweden / Q000453:epidemiology
chemical_list: D002273:Carcinogens; D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls