Aryl Hydrocarbon Receptor Expression Is Associated with a Family History of Upper Gastrointestinal Tract Cancer in a High-Risk Population Exposed to Aromatic Hydrocarbons

Roth, Mark J.; Wei, Wenqiang; Baer, Jessica; Abnet, Christian C.; Wang, Guoqing; Sternberg, Lawrence R.; Warner, Andrew C.; Johnson, Laura Lee; Lü, Ning; Giffen, Carol; Dawsey, Sanford M.; Qiao, You‐Lin; Cherry, James

doi:10.1158/1055-9965.epi-08-1098

Cited by 17 publications

(10 citation statements)

References 40 publications

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“…PAH exposure 33 and occupational exposure to combustion products 33,34 have been suggested as risk factors for esophageal squamous-cell carcinoma. PAHs or dust could be deposited in the airway region and then swallowed, thereby directly acting on the esophageal mucosa 33,35 and potentially explaining the finding of an increased risk of esophageal cancer. Alcohol and tobacco smoking are well-known risk factors for esophageal cancer, 36,37 but are not likely to have had a major influence on the risk estimates.…”

Section: Esophageal Cancermentioning

confidence: 99%

Cancer Incidence in a Cohort of Swedish Chimney Sweeps, 1958–2006

Hogstedt

Jansson²,

Hugosson³

et al. 2013

Am J Public Health

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Objectives. We examined cancer incidence in an expanded cohort of Swedish chimney sweeps. Methods. We added male chimney sweep trade union members (1981–2006) to an earlier cohort (employed 1918–1980) and linked them to nationwide registers of cancer, causes of deaths, and total population. The total cohort (n = 6320) was followed from 1958 through 2006. We estimated standardized incidence ratios (SIRs) using the male Swedish population as reference. We estimated exposure as years of employment and analyzed for exposure–response associations by Poisson regression. Results. A total of 813 primary cancers were observed versus 626 expected (SIR = 1.30; 95% confidence interval = 1.21, 1.39). As in a previous follow-up, SIRs were significantly increased for cancer of the esophagus, liver, lung, bladder, and all hematopoietic cancer. New findings included significantly elevated SIRs for cancer of the colon, pleura, adenocarcinoma of the lung, and at unspecified sites. Total cancer and bladder cancer demonstrated positive exposure–response associations. Conclusions. Exposure to soot and asbestos are likely causes of the observed cancer excesses, with contributions from adverse lifestyle factors. Preventive actions to control work exposures and promote healthier lifestyles are an important priority.

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Section: Esophageal Cancermentioning

confidence: 99%

Cancer Incidence in a Cohort of Swedish Chimney Sweeps, 1958–2006

Hogstedt

Jansson²,

Hugosson³

et al. 2013

Am J Public Health

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“…The Iranian study detected 1 hydroxypyrene glucuronide (a stable metabolite of PAHs) in 83% of the subjects. The Chinese studies detected greater concentrations of PAH-DNA adducts (26), and elevated aryl hydrocarbon receptor gene expression (27) in esophageal cell samples from patients compared to healthy control subjects. While increase in environmental pollution by PAHs has been attributed to esophageal cancer in Iran, high levels of carcinogenic PAHs in food (28), and indoor air pollution (domestic heating with coal) have been implicated as the causative factors for esophageal cancer in China.…”

Section: Epidemiological Studiesmentioning

confidence: 99%

Polycyclic Aromatic Hydrocarbons and Digestive Tract Cancers: A Perspective

Diggs

Huderson

Harris

et al. 2011

Journal of Environmental Science and Health, Part C

234

107

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Cancers of the colon are most common in the Western world. In majority of these cases, there is no familial history and sporadic gene damage seems to play an important role in the development of tumors in the colon. Studies have shown that environmental factors, especially diet, play an important role in susceptibility to GI tract cancers. Consequently, environmental chemicals that contaminate food or diet during its preparation becomes important in the development of GI cancers. Polycyclic aromatic hydrocarbons (PAHs) are one such family of ubiquitous environmental toxicants. These pollutants enter the human body through consumption of contaminated food, drinking water, inhalation of cigarette smoke, automobile exhausts, and contaminated air from occupational settings. Among these pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs and their ability to cause toxicity and breast or lung cancer have been published, aspects on contribution of diet, smoking and other factors towards development of digestive tract cancers and strategies to assess risk from exposure to PAHs have received much less attention. This review, therefore, focuses on dietary intake of PAHs in humans, animal models, and cell cultures used for GI cancer studies along with epidemiological findings. Bioavailability and biotransformation processes, which influence the disposition of PAHs in body and the underlying causative mechanisms of GI cancers, are also discussed. The existing data gaps and scope for future studies is also emphasized. This information is expected to stimulate research on mechanisms of sporadic GI cancers caused by exposure to environmental carcinogens.

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“…Given that ABCG2 upregulation may lead to treatment failure when HDACI (romidepsin) is used in combination with other chemotherapeutic agents, strategies could be designed to modulate the AhR pathway therapeutically for the circumvention of drug resistance. Moreover, because constitutive overexpression of AhR is commonly observed in several cancer types including lung and esophageal cancers (56,57), the involvement of this AhR-mediated upregulation of ABCG2 in the acquired multidrug resistance and poor prognosis of these cancers may deserve investigation.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of ABCG2 by Romidepsin via the Aryl Hydrocarbon Receptor Pathway

Robey

Zhan

et al. 2011

Molecular Cancer Research

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Histone deacetylase inhibitors (HDACI) are promising anticancer agents and their use in combination with conventional anticancer drugs is currently under investigation. We previously reported cell line-specific upregulation of ABCG2, a multidrug resistance transporter shown to control oral bioavailability and CNS penetration, by the HDACI romidepsin, although the precise mechanism in a particular cell line remains to be determined. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by numerous environmental contaminants and has been shown to be a client protein of heat shock protein 90 (Hsp90). A xenobiotic response element was defined in the ABCG2 promoter and was shown to mediate AhR signaling. Activated AhR was found to be associated with the ABCG2 promoter only in cell line models that respond to romidepsin with ABCG2 upregulation. Our data suggest that romidepsin acetylated Hsp70 and inhibited the chaperone function of Hsp90, thereby allowing the dissociation of AhR from Hsp90. The dissociation of AhR from Hsp90 may be a prerequisite for the differential upregulation of ABCG2 by romidepsin. Increasing our understanding of the mechanism(s) governing differential upregulation of ABCG2 in response to romidepsin could provide an insight into strategies needed to tackle resistance to HDACIs in cancer therapeutics. Mol Cancer Res; 9(4); 516-27. Ó2011 AACR.

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Aryl Hydrocarbon Receptor Expression Is Associated with a Family History of Upper Gastrointestinal Tract Cancer in a High-Risk Population Exposed to Aromatic Hydrocarbons

Cited by 17 publications

References 40 publications

Cancer Incidence in a Cohort of Swedish Chimney Sweeps, 1958–2006

Cancer Incidence in a Cohort of Swedish Chimney Sweeps, 1958–2006

Polycyclic Aromatic Hydrocarbons and Digestive Tract Cancers: A Perspective

Upregulation of ABCG2 by Romidepsin via the Aryl Hydrocarbon Receptor Pathway

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