Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV)

Pan, Wen Chi; Wu, Chih-Da; Chen, Mu Jean; Huang, Yue; Chen, Chien Jen; Su, Huey Jen; Yang, Hwai I.

doi:10.1093/jnci/djv341

Cited by 133 publications

(111 citation statements)

References 41 publications

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“…Only PM 2.5 was positively associated with GGT (5.1% increase (95% CI: 0.1% to 10.4%) per 2.8 µg/m 3 increment in annual average PM 2.5 ) and no significant associations were found for other air pollutants or liver enzymes 24. A Taiwanese study found long-term exposure to PM 2.5 was positively associated with ALT levels (44.17% increase (95% CI: 23.21% to 68.68%) per 12.2 µg/m 3 PM 2.5 increment) and the ALT significantly mediated the association between PM 2.5 and incident hepatocellular carcinoma observed in this study 17. A recent study among 74 American children found that traffic-related air pollution was not associated with AST or ALT, but associated with cytokeratin-18, a marker of hepatocellular apoptosis 25.…”

Section: Discussioncontrasting

confidence: 74%

Long-term exposure to ambient fine particulate matter and liver enzymes in adults: a cross-sectional study in Taiwan

et al. 2019

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ObjectivesAnimal experiments indicate that exposure to particulate matter (PM) can induce hepatotoxic effects but epidemiological evidence is scarce. We aimed to investigate the associations between long-term exposure to PM air pollution and liver enzymes, which are biomarkers widely used for liver function assessment.MethodsA cross-sectional analysis was performed among 351 852 adult participants (mean age: 40.1 years) who participated in a standard medical screening programme in Taiwan. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) levels were measured. A satellite-based spatio-temporal model was used to estimate the concentrations of ambient fine particles (PM with an aerodynamic diameter ≤2.5 µm, PM2.5) at each participant’s address. Linear and logistic regression models were used to investigate the associations between PM2.5 and the liver enzymes with adjustment for a wide range of potential confounders.ResultsAfter adjustment for confounders, every 10 µg/m3 increment in 2-year average PM2.5 concentration was associated with 0.02%(95% CI: −0.04% to 0.08%), 0.61% (95% CI: 0.51% to 0.70%) and 1.60% (95% CI: 1.50% to 1.70%) increases in AST, ALT and GGT levels, respectively. Consistently, the odds ratios of having elevated liver enzymes (>40 IU/L) per 10 µg/m3 PM2.5 increment were 1.06 (95% CI: 1.04 to 1.09), 1.09 (95% CI: 1.07 to 1.10) and 1.09 (95% CI: 1.07 to 1.11) for AST, ALT and GGT, respectively.ConclusionsLong-term exposure to PM2.5 was associated with increased levels of liver enzymes, especially ALT and GGT. More studies are needed to confirm our findings and to elucidate the underlying mechanisms.

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Section: Discussioncontrasting

confidence: 74%

Long-term exposure to ambient fine particulate matter and liver enzymes in adults: a cross-sectional study in Taiwan

et al. 2019

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“…PM 2.5 induced the metastatic capabilities of lung cancer, including migration and invasion (11). The patient observational reports indicated that PM 2.5 exposure was associated with HCC via chronic liver inflammation (12). The incidence of HCC may also be associated with PM 2.5 , therefore the effects of PM 2.5 on HCC cells require further study.…”

Section: Introductionmentioning

confidence: 99%

Atmospheric particulate matter2.5 promotes the migration and invasion of hepatocellular carcinoma cells

et al. 2017

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Epidemiological data has demonstrated that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 µm (PM2.5) is associated with cancer incidence. However, the precise mechanisms underlying PM2.5-mediated hepatocellular carcinoma cancer (HCC) migration and invasion remain unclear. The aim of the present study was to explore the response of the HCC cell lines HepG2 and HuH-7 to PM2.5 exposure. The results revealed that PM2.5 treatment promoted the migration and invasion of HCC cells, in addition to increasing protein levels of matrix metalloproteinase (MMP)-13. Additionally, PM2.5 induced intracellular reactive oxygen species formation in HCC cells. Further investigation revealed that phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) increased in response to PM2.5 exposure in HCC cells, and the AKT antagonist LY294002 reduced PM2.5-induced migration, invasion and MMP-13 expression. In addition, the data from the present study demonstrated that high concentrations of PM2.5 decreased the proliferation of normal HL7702 hepatocyte cells and promoted apoptosis. These results indicate that the activation of AKT by PM2.5 results in MMP-13 overexpression, and stimulates HCC cell migration and invasion. In conclusion, the results from the present study demonstrate that PM2.5 promotes HCC development and elucidate a potential underlying molecular mechanism for this effect.

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“…The liver may be a target as pm 2.5 can induce oxidative stress, inflammation, genotoxicity, and accelerate liver inflammation and steatosis, driving the development and progression of liver cancer . For example, pm 2.5 exposure has been linked to increased serum levels of hepatic enzymes such as alanine aminotransferase, which is a marker of liver damage and a predictor of hepatocellular carcinoma (HCC), the most common liver cancer . Long‐term pm 2.5 exposures have recently been linked to an increased incidence of HCC, but the effects of pm 2.5 exposure on survival of HCC have not been investigated.…”

mentioning

confidence: 99%

“…For example, pm 2.5 exposure has been linked to increased serum levels of hepatic enzymes such as alanine aminotransferase, which is a marker of liver damage and a predictor of hepatocellular carcinoma (HCC), the most common liver cancer . Long‐term pm 2.5 exposures have recently been linked to an increased incidence of HCC, but the effects of pm 2.5 exposure on survival of HCC have not been investigated. We hypothesized that pm 2.5 exposure accelerates the progression of HCC and decreases survival after the diagnosis of liver cancer.…”

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confidence: 99%

Particulate matter air pollution and liver cancer survival

Deng

Eckel

Liu

et al. 2017

Intl Journal of Cancer

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Particulate air pollution (PM) exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. 20,221 California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000–2009 were used to examine the effect of exposure to ambient PM with diameter less than 2.5µm (PM2.5) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM2.5 to all-cause and liver cancer-specific mortality linearly and non-linearly— overall and stratified by stage at diagnosis (local, regional, and distant)—adjusting for potential individual and geospatial confounders. PM2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all-cause mortality HR associated with a 1 standard deviation (5.0 µg/m3) increase in PM2.5 was 1.18 (95% CI: 1.16 – 1.20); 1.31 (95% CI:1.26 – 1.35) for local stage, 1.19 (95% CI:1.14 – 1.23) for regional stage, and 1.05 (95% CI:1.01 – 1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer-specific mortality and PM2.5 were slightly attenuated compared to all-cause mortality, but with the same patterns. Exposure to elevated PM2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations.

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Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV)

Abstract: Long-term PM2.5 exposure increased the risk for liver cancer, and chronic inflammation of the liver may underlie the pathogenesis.

Cited by 133 publications

References 41 publications

Long-term exposure to ambient fine particulate matter and liver enzymes in adults: a cross-sectional study in Taiwan

Long-term exposure to ambient fine particulate matter and liver enzymes in adults: a cross-sectional study in Taiwan

Atmospheric particulate matter2.5 promotes the migration and invasion of hepatocellular carcinoma cells

Particulate matter air pollution and liver cancer survival

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