A review of Agent Orange and its associated oncologic risk of genitourinary cancers

Chang, Chrystal; Benson, M. K. D.; Fam, Mina

doi:10.1016/j.urolonc.2017.08.029

Cited by 14 publications

(21 citation statements)

References 31 publications

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“…A recent large-scale evaluation of Agent Orange and cancer incidence and mortality among Korean veterans found significant excesses of all-site cancer incidence and mortality, but null findings for RCC incidence and mortality . Similarly, a review of Agent Orange and genitourinary cancers that included eight studies of renal cancer found that there was insufficient evidence to determine whether Agent Orange was associated with RCC (Chang et al 2017), with small numbers of exposed cases in most studies and only one of the eight studies finding a statistically significant association (Kogan and Clapp 1988).…”

Section: Discussionmentioning

confidence: 99%

Occupational Pesticide Use and Risk of Renal Cell Carcinoma in the Agricultural Health Study

Andreotti

Freeman

Shearer

et al. 2020

Environ Health Perspect

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BACKGROUND: Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides. OBJECTIVE: We evaluated the lifetime use of individual pesticides and the incidence of RCC. METHODS: We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993-1997) and the end of follow-up (2014-2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures. RESULTS: There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged RR IWD Tertile 3 = 2:92 (95% CI: 1.65, 5.17; p trend = 0:001)], with similar risk estimates for lagged exposure [20-y lag RR IWD Tertile 3 = 3:37 (95% CI: 1.83, 6.22; p trend = 0:001)]. In 20-y lagged analyses, we also found exposure-response associations with chlorpyrifos [

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Section: Discussionmentioning

confidence: 99%

Occupational Pesticide Use and Risk of Renal Cell Carcinoma in the Agricultural Health Study

Andreotti

Freeman

Shearer

et al. 2020

Environ Health Perspect

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“…In humans, TCDD exposure is associated with a plethora of adverse health outcomes, such as chloracne, immunosuppression, and cancer 12–15 . Accumulating evidence suggests that TCDD and other dioxin-like chemicals are also associated with increased incidence of metabolic disorders such as nonalcoholic fatty-liver disease (NAFLD) 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice

Dornbos

Jurgelewicz

Fader

et al. 2019

Sci Rep

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.

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“…18,29 There is also some evidence suggesting a role in lung, head and neck, renal cell, bladder, and prostate cancer risk, but those associations remain under investigation. 17 Previous studies in cohorts of patients treated in the Veterans Affairs (VA) system, have found a slight decrease in age at diagnosis, higher incidence of stage IV disease and lower rates of biochemical control, but no differences in overall survival or other clinical outcomes. 17,30,31 We report here for the first time a clear association between Agent Orange exposure and prostate cancer diagnosis, metastasis and specific mortality among MVP participants.…”

Section: Discussionmentioning

confidence: 99%

“…17 Previous studies in cohorts of patients treated in the Veterans Affairs (VA) system, have found a slight decrease in age at diagnosis, higher incidence of stage IV disease and lower rates of biochemical control, but no differences in overall survival or other clinical outcomes. 17,30,31 We report here for the first time a clear association between Agent Orange exposure and prostate cancer diagnosis, metastasis and specific mortality among MVP participants. Additionally, it was not previously known how prostate cancer risks associated with Agent Orange exposure might interact with inherited risk.…”

Section: Discussionmentioning

confidence: 99%

“…Agent Orange, a mixture of herbicides used predominately in the Vietnam war to clear dense vegetation and destroy food crops, contains a dioxin, a known carcinogen that has been proposed to increase prostate cancer risk among US Vietnam War veterans. 17,18 Intriguing recent studies suggest a healthy lifestyle can mitigate a high inherited prostate cancer risk and risk of lethal prostate cancer, as shown in a combined analysis of two cohorts of health professionals. 19 A healthy lifestyle, including regular exercise and a wholesome diet (low in saturated fats but high in fruits, vegetables, low-fat dairy and fish) is known to reduce the risks of cardiovascular disease in addition to the development of colorectal and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Healthy lifestyle and prostate cancer risk in the Million Veteran Program

Pagadala

Lui

Lynch³

et al. 2022

Preprint

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Prostate cancer risk is understood to be mostly unchangeable and inherited. Currently, the strongest known risk factors for developing prostate cancer are age, race/ethnicity, family history and some specific genetic elements. The impact of healthy lifestyle on prostate cancer survivorship is a research priority because of potential impact on quality of life, progression of disease, and tolerance to treatment. Several studies have identified an association between tobacco use, low physical activity, and obesity with increased risk of prostate cancer progression and prostate cancer-related death. Additionally, environmental exposure to carcinogens is known to increase cancer risk including Agent Orange, a chemical agent used in the Vietnam War (1955-1975). Recent studies suggest a healthy lifestyle can mitigate a high inherited prostate cancer risk and risk of lethal prostate cancer, as shown in a combined analysis of two cohorts of health professionals. In this study, we utilize data from over 870,000 participants in the Million Veteran Program (MVP) to investigate the association of modifiable, environmental, and other factors on prostate cancer risk in a diverse population when accounting for the common major inherited risk factors: race/ethnicity, family history, and polygenic risk. The healthy lifestyle score (Range 0-4) is tabulated using answers to 60 questions in the MVP database for each participant, with a point assigned for each of the following: not a current smoker, healthy weight (body mass index [BMI] ≥ 30), strenuous activity >4 days per week, and a healthier than average diet. In this cohort, race/ethnicity, family history were associated with higher prostate cancer risks. When accounting for race/ethnicity and family history of prostate cancer, Agent Orange exposure was an independent factor for prostate cancer diagnosis (HR 1.06, 95% CI 1.04-1.09). Healthy lifestyle score was associated with a lower risk of metastatic prostate cancer (HR 0.80, 95% CI 0.77-0.82) and of fatal prostate cancer (HR 0.81, 95% CI 0.76-0.85) in the MVP cohort. Importantly, healthy lifestyle score was independently associated with reduced metastatic (HR 0.90, 95% CI 0.87-0.93) and fatal prostate cancer (HR 0.89, 95% CI 0.83-0.96) when accounting for race/ethnicity, family history, and genetic risk (PHS290). We report that environmental exposures are independently associated with prostate cancer risk when accounting for major inherited risk factors (family history, ancestry, and polygenic risk). Adherence to a healthy lifestyle is associated with lower risk of prostate cancer and with lower risk of dying from prostate cancer, which offsets high inherited risk.

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A review of Agent Orange and its associated oncologic risk of genitourinary cancers

Cited by 14 publications

References 31 publications

Occupational Pesticide Use and Risk of Renal Cell Carcinoma in the Agricultural Health Study

Occupational Pesticide Use and Risk of Renal Cell Carcinoma in the Agricultural Health Study

Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice

Healthy lifestyle and prostate cancer risk in the Million Veteran Program

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