Agricultural exposures and risk of childhood neuroblastoma: a systematic review and meta-analysis.

While neuroblastoma accounts for an estimated 8% of childhood cancers, it causes about 15% of childhood cancer deaths in the United States. The role of agricultural exposures in the development of neuroblastoma is unclear. We conducted a systematic review and meta-analysis of studies examining the relationship between agricultural exposures and neuroblastoma. MEDLINE, EMBASE, Scopus, and Google Scholar were searched in February 2022, identifying 742 publications. Seventeen articles met the inclusion criteria; all were published between 1985 and 2020 and included 14 case-control, one cross-sectional, and two cohort studies. Random and fixed effects models were used to calculate summary odds ratios (sORs) and 95% confidence intervals (CIs). An increased odds of developing neuroblastoma with parental exposure to any pesticides (sOR = 1.25, 95% CI: 1.03-1.48; 4 studies), insecticides (sOR = 1.55, 95% CI: 1.19-1.91; 3 studies), and residential exposure to crops/vegetables (sOR = 1.04, 95% CI: 1.01-1.06; 2 studies) was seen. Heterogeneity was low in all analyses, and no publication bias was evident. No significant associations were found with agricultural occupations, herbicides, and agricultural dusts. The studies were limited by exposure measurements and small sample sizes. Further studies are needed to explore mechanisms in the development of neuroblastoma in children with parental agricultural exposures, especially pesticides, and to improve methods of measuring agricultural-related exposures.

Predictors of cancer risky and preventive behaviors among the Nebraska farmers population.

PURPOSE: Previous studies on cancer risk among agricultural producers have focused on occupational exposures, with only a few studies examining behavioral factors. The aim of this study was to understand cancer risky and preventative behaviors among the large farming population in Nebraska. METHODS: A statewide cross-sectional study of farmers in Nebraska aged 19 and older was conducted in 2019 (n = 782). Multivariable logistic regression was used to examine factors associated with being up to date on cancer screening and with cancer risky and preventive behaviors. FINDINGS: The 93.68% of the Nebraska farmers population do not meet the daily recommended consumption of fruits and vegetables, and 70.14% reported regular alcohol consumption. The proportion of adults up to date on cancer screening was 79.57% for breast, 67.55% for cervical, 85.54% for colorectal, and 46.05% for skin cancers. Compared to women, men had a higher odds of heavy alcohol consumption (aOR 2.96, 95% CI 1.94-4.56) and ever smoking 100 or more cigarettes (aOR 1.66, 95% CI 1.03-2.73). The odds of being current with skin cancer screening was higher among those with higher incomes (aOR 1.77, 95% CI 1.06-3.01). Compared to men aged 50-64, the odds of being current with prostate cancer screening was higher among men aged 65-74 (aOR: 2.65, 95% CI 1.10-7.31) and 75 and older (aOR: 7.73, 95% CI 2.03-51.73). CONCLUSIONS: Disparities in cancer screening and risk and preventive behaviors exist among farmers in Nebraska. The study highlights a need for continuing efforts to improve preventive cancer behaviors targeted to the farming population.

Differential methylation patterns in lean and obese non-alcoholic steatohepatitis-associated hepatocellular carcinoma.

BACKGROUND: Nonalcoholic fatty liver disease affects about 24% of the world's population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. METHODS: In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice. Differentially methylated regions were determined using reduced representation bisulfite sequencing. RESULTS: A larger number of differentially methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice compared to the non-obese mice. No overlap existed in the DMRs with the largest methylation differences between the two models. In lean NASH-HCC, methylation differences were seen in genes involved with cancer progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in hypomethylated DMRs in the obese NASH-HCC. CONCLUSIONS: These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism.

Predictors of behavioral cancer risk factors and preventive behaviors among Nebraskans.

BACKGROUND: The overall incidence rate of cancer in Nebraska is higher than the national average with cancer being the second leading cause of death in the state. Interventions are required to reduce the cancer burden; however, further research is first needed to identify behavioral cancer risk factors and preventive behaviors among Nebraskans that can be targeted. METHODS: A statewide cross-sectional survey of Nebraskans aged 19 and older was conducted in 2019 using an address-based sampling method (n = 1640). Multivariable logistic regression was used to examine factors associated with being up-to-date on cancer screening and with behavioral cancer risk factors and preventive behaviors. RESULTS: 93.42% of Nebraskans did not meet the daily recommended consumption of fruits and vegetables, and 71.51% did not meet weekly physical activity guidelines. The proportion of adults up to date on cancer screening was 64.57% for breast, 68.83% for cervical, 69.01% for colorectal, and 24.07% for skin cancers. Individuals 65-74 (OR: 3.40, 95% CI: 1.52-7.62) and 75 or older (OR: 3.30, 95% CI: 1.35-8.07) were more likely to be current with their colorectal cancer screening compared to ages 50-64. Hispanics were less likely to be current with mammograms (OR: 0.06, 95% CI: 0.01-0.71) and ever screened for cervical cancer (OR:0.13, 95% CI: 0.02-0.94) compared to Non-Hispanic Whites. CONCLUSIONS: Disparities in cancer screening and risk and preventive behaviors exist in Nebraska. IMPACT: The study highlights a need for continuing efforts to improve preventive cancer behaviors for the entire population as well as some high-risk populations in Nebraska.

Differential progression of unhealthy diet-induced hepatocellular carcinoma in obese and non-obese mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood. METHODS: In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice. RESULTS: Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice. CONCLUSIONS: Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis.