Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data

Abstract

Background Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. U.S. studies examining self-reported pesticide exposure in relation to HCC have demonstrated inconclusive results. We aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS). Methods Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. Potential confounders were extracted from Medicare claims. From 1974 to 2008, pounds (1 pound represents 0.45 kg) of applied organophosphate, organochlorine, and carbamate pesticides provided in PURs were aggregated to the ZIP Code level using area weighting in a GIS. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Agricultural residents were defined as living in ZIP Codes with a majority area intersecting agricultural land cover according to the 1992, 2001, and 2006 National Land Cover Database (NLCD) rasters. Multivariable conditional logistic regression was used to estimate the association between pesticide exposure and HCC. Results Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53 kg/km2 of organochlorine pesticides (75th percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87, 95% confidence interval [CI] 1.17, 2.99; p=0.0085). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76, 95% CI 1.58, 4.82; p=0.0004), but not associated with HCC among females (adjusted OR 0.83, 95% CI 0.35, 1.93; p=0.6600) (interaction p=0.0075). Conclusions This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females.

Pesticide exposure and liver cancer: a review

“…VoPham et al (2015) assessed pesticide exposure by combining residential ZIP Codes with a pesticide exposure database in a geographic information system (GIS) in the U.S. [53]. ZIP Code-level organochlorine pesticide exposure ≥14.53 kg/km 2 compared to <14.53 kg/km 2 (adjusted OR 1.87, 95% CI 1.17, 2.99) was associated with a statistically significant increase in HCC risk among individuals residing in agriculturally intensive areas in the U.S., adjusting for liver disease and diabetes and stratifying by the matching factors of age, sex, race, duration of California residence, and year [53].…”

“…VoPham et al. (2015) did not have access to individual-level occupation, a potential confounder [53]. There was a statistically significant interaction between ZIP Code-level organochlorine pesticide exposure and sex (p=0.0075), where pesticide exposure was associated with a statistically significant increase in HCC risk among males, but no association was observed among females [53].…”

“…VoPham et al (2015) (referenced earlier) reported no association between ZIP Code-level organophosphate pesticides or carbamate pesticides and HCC in the U.S. [53]. …”

“…VoPham et al (2015) (referenced earlier) reported that combined ZIP Code-level exposure to organochlorine, organophosphate, and carbamate pesticides was not associated with HCC risk in the U.S. after adjustment (Table 2) [53]. …”

Occupational exposure to carcinogens: Benzene, pesticides and fibers

“…Epidemiological studies have shown that pesticide exposure may increase the risk of developing hepatocellular carcinoma (HCC), through mechanisms of genotoxicity, cytotoxicity, tumor promotion, immunotoxicity and hormonal action (83). In particular, exposure to organochlorine pesticides has been associated with an increased risk of developing HCC among California male residents of agriculturally intensive areas (102). It has also been observed that organochlorine pesticides possess carcinogenicity and can induce liver cancer (103).…”