High Incidence Of Liver Cancer Research Articles

Cancer patterns in Arua district, Uganda: a hospital-based retrospective study.

Cancer is the second leading cause of mortality with over 19 million cases and 10 million deaths worldwide. Available data on cancer patterns in Uganda are through modelling of data from two population-based cancer registries (PBCRs) representing only about 10% of the cancer situation in Uganda. This study sought to determine the common types of cancer among adults and children in Arua District over a 5-year period (2017-2021). Retrospective cohort chart review and 'catchment population approach' were employed. All newly diagnosed cancer patients from Arua between 2017 and 2021 were included in this study. Data were collected using Redcap whereas management and analysis were conducted using Stata 17. Cancer patterns were computed as frequencies and percentages and the interest was in finding out the common cancers among adults (above 19 years) and children (0-19 years). Over the 5-year study period, a total of 1,118 new cancer cases were registered, with slightly more females (52.1%). The top five common cancers irrespective of sex and age were: liver cancer (13.7%), cervical (11.8%), breast (10.7%), oesophagus (10.5%) and Burkitt's lymphoma (BL) (6.4%). In this study, 15.3% (n = 171) of the study participants were children. The top five common childhood cancers included BL (42%), leukemia (10.5%), other lymphomas (9.4%), osteosarcoma (4.7%) and nephroblastoma (3%). There is a high incidence of liver cancer in Arua district. The high levels of cervical, breast and oesophagus cancer were consistent with what is reported by the two PBCRs in Uganda. However, BL could be due to the presence of a BL treatment centre at Kuluva hospital in Arua. Cancer interventions in Arua should therefore be targeted towards liver, cervix, breast, and oesophagus cancer and furthering research on the reason for the high incidence of liver cancer.

G6PD and machine learning algorithms as prognostic and diagnostic indicators of liver hepatocellular carcinoma

BackgroundLiver Hepatocellular carcinoma (LIHC) exhibits a high incidence of liver cancer with escalating mortality rates over time. Despite this, the underlying pathogenic mechanism of LIHC remains poorly understood.Materials & methodsTo address this gap, we conducted a comprehensive investigation into the role of G6PD in LIHC using a combination of bioinformatics analysis with database data and rigorous cell experiments. LIHC samples were obtained from TCGA, ICGC and GEO databases, and the differences in G6PD expression in different tissues were investigated by differential expression analysis, followed by the establishment of Nomogram to determine the percentage of G6PD in causing LIHC by examining the relationship between G6PD and clinical features, and the subsequent validation of the effect of G6PD on the activity, migration, and invasive ability of hepatocellular carcinoma cells by using the low expression of LI-7 and SNU-449. Additionally, we employed machine learning to validate and compare the predictive capacity of four algorithms for LIHC patient prognosis.ResultsOur findings revealed significantly elevated G6PD expression levels in liver cancer tissues as compared to normal tissues. Meanwhile, Nomogram and Adaboost, Catboost, and Gbdt Regression analyses showed that G6PD accounted for 46%, 31%, and 49% of the multiple factors leading to LIHC. Furthermore, we observed that G6PD knockdown in hepatocellular carcinoma cells led to reduced proliferation, migration, and invasion abilities. Remarkably, the Decision Tree C5.0 decision tree algorithm demonstrated superior discriminatory performance among the machine learning methods assessed.ConclusionThe potential diagnostic utility of G6PD and Decision Tree C5.0 for LIHC opens up a novel avenue for early detection and improved treatment strategies for hepatocellular carcinoma.

Cancer incidence in World Trade Center rescue and recovery workers by race and ethnicity.

It is unclear whether differences in health outcomes by racial and ethnic groups among World Trade Center (WTC) rescue and recovery workers reflect those of the population of New York State (NYS) or show distinct patterns. We assessed cancer incidence in WTC workers by self-reported race and ethnicity, and compared it to population figures for NYS. A total of 61,031 WTC workers enrolled between September 11, 2001andJanuary 10, 2012were followed to December 31, 2015. To evaluate the association between race/ethnicity and cancer risk, Poissonregression analysis was used to estimate hazard ratios (HR) adjusted for WTC exposure, age, calendar year, sex and, for lung cancer, cigarette smoking. In comparison to Whites, Black workers had a higher incidence of prostate cancer (HR = 1.99, 95% CI = 1.69-2.34) and multiple myeloma (HR = 3.57, 95%CI = 1.97-6.45), and a lower incidence of thyroid (HR = 0.41, 95%CI = 0.22-0.78) and colorectal cancer (HR = 0.57; 95%CI = 0.33-0.98). Hispanic workers had a higher incidence of liver cancer (HR = 4.03, 95%CI = 2.23-7.28). Compared with NYS population, White workers had significantly higher incidence of prostate cancer (HR = 1.26, 95%CI = 1.18-1.35) and thyroid cancer (HR = 1.80, 95%CI = 1.55-2.08), while Black workers had significantly higher incidence of prostate cancer (HR = 1.22, 95%CI = 1.05-1.40). Cancer incidence in WTC workers generally reflects data from the NYS population, but some differences were identified that merit further investigation.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality

Approximately 65% of adults in the US consume sugar-sweetened beverages daily. To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Unified semicompeting risks analysis of hepatitis natural history through mediation modeling.

Natural history of hepatitis B or C is comprised of multiple milestones such as liver cirrhosis and liver cancer. To fully characterize its natural course, semicompeting risks represent a common problem where liver cirrhosis and liver cancer are both of interest, but only the former may be censored by the latter. Copula, frailty and multistate models serve as well-established analytics for semicompeting risks. Here, we cast the semicompeting risks in a mediation framework, with liver cirrhosis as a mediator and liver cancer as an outcome. We define the indirect and direct effects as the effects of an exposure on the liver cancer incidence mediated and not mediated through liver cirrhosis, respectively. With the estimands derived as conditional probabilities, we derive respective expressions under the copula, frailty, and multistate models. Next, we propose estimators based on nonparametric maximum likelihood or U-statistics and establish their asymptotic results. Numerical studies demonstrate that the efficiency of copula models leads to potential bias due to model misspecification. Moreover, the robustness of frailty models is accompanied by a loss in efficiency, and multistate models balance the efficiency and robustness. We demonstrate the utility of the proposed methods by a hepatitis study, showing that hepatitis B and C lead to a higher incidence of liver cancer by increasing liver cirrhosis incidence. Thus, mediation modeling provides a unified framework that accommodates various semicompeting risks models.

Decrease in liver cancer incidence rates in Bamako, Mali over 28 years of population-based cancer registration (1987-2015).

BACKGROUNDPrimary liver cancer is common in West Africa due to endemic risk factors. However, epidemiological studies of the global burden and trends of liver cancer are limited. We report changes in trends of the incidence of liver cancer over a period of 28 years using the population-based cancer registry of Bamako, Mali.AIMTo assess the trends and patterns of liver cancer by gender and age groups by analyzing the cancer registration data accumulated over 28 years (1987-2015) of activity of the population-based registry of the Bamako district.METHODSData obtained since the inception of the registry in 1987 through 2015 were stratified into three periods (1987-1996, 1997-2006, and 2007-2015). Age-standardized rates were estimated by direct standardization using the world population. Incidence rate ratios and the corresponding 95% confidence intervals (CI) were estimated using the early period as the reference (1987-1996). Joinpoint regression models were used to assess the annual percentage change and highlight trends over the entire period (from 1987 to 2015).RESULTSAmong males, the age-standardized incidence rates significantly decreased from 19.41 (1987-1996) to 13.12 (1997-2006) to 8.15 (2007-2015) per 105 person-years. The incidence rate ratio over 28 years was 0.42 (95%CI: 0.34-0.50), and the annual percentage change was -4.59 [95%CI: (-6.4)-(-2.7)]. Among females, rates dropped continuously from 7.02 (1987-1996) to 2.57 (2007-2015) per 105 person-years, with an incidence rate ratio of 0.37 (95%CI: 0.28-0.45) and an annual percentage change of -5.63 [95%CI: (-8.9)-(-2.3)].CONCLUSIONThe population-based registration showed that the incidence of primary liver cancer has steadily decreased in the Bamako district over 28 years. This trend does not appear to result from biases or changes in registration practices. This is the first report of such a decrease in an area of high incidence of liver cancer in Africa. This decrease may be explained by the changes and diversity of diet that could reduce exposure to aflatoxins through dietary contamination in this population.

Environmental Exposure to Cyanobacteria Hepatotoxins in a Pacific Island Community: A Cross-Sectional Assessment.

(1) Background: Cyanobacteria produce a wide range of secondary metabolites, including tumor-promoting hepatotoxins. We recently reported evidence of an independent association between oral cyanobacteria and hepatocellular carcinoma in a U.S. population. We sought to characterize the nature, sources, and health correlates of cyanotoxin exposure in the U.S. Pacific Island territory of Guam, which has a high incidence of liver cancer. (2) Methods: Seventy-four adult males and females were enrolled in a cross-sectional study to quantify cyanotoxins in saliva, urine, and blood and their correlation with health behaviors, medical history, and environmental exposures. Plant samples were collected from locations throughout the island. Microcystin/nodularin (MC/NOD), cylindrospermopsin (CYN), and anabaenopeptin (AB) were measured in biospecimens and in plant extracts by ELISA. (3) Results: Overall, among study participants MC/NOD were detected in 53.9% of saliva, 7.5% of urine, and 100% of serum.; CYN in 40.0% of saliva, 100.0% of urine, and 70.4% of serum; AB in 30.8% of saliva, 85% of urine, and 92.6% of serum. Salivary MC/NOD levels were significantly higher in individuals using municipal tap water as their primary source of drinking water; both salivary and urinary MC/NOD levels were higher in those not using store-bought/commercial water. Urine MC/NOD levels were highest among individuals consuming fruits and vegetables exclusively from local sources. Urine MC/NOD levels were elevated in individuals with hypertension and hyperlipidemia and salivary MC/NOD in those with recent alcohol consumption. Cyanotoxins were prevalent in plant samples including MC/NOD (46.6%), CYN (35.1%), and AB (51.7%). (4) Conclusions: Our study provides evidence that exposure to cyanobacterial hepatotoxins, including tumor promoters, may be prevalent in Guam and may originate from environmental sources. Population-based epidemiologic studies are needed to investigate the role of cyanotoxins in liver cancer development.

Physiological alteration and the expression of fibrogenesis-proinflammatory genes in hepatocellular carcinoma patients with chronic hepatitis C and onset metabolic syndrome: a preliminary report at Saiful Anwar General Hospital Malang

Hepatocellular carcinoma (HCC) is one type of cancer that is included in the fifth order of cancer that causes death in the world. The highest incidence of liver cancer is found in men. Liver function related to the metabolism of various endogenous and exogenous substances is prone to chronic inflammatory stimulation, one of which is hepatitis C virus (HCV) infection. TGF-β1, NOX4, and TNF-α are three potential genes responsible for regulating chronic inflammation and fibrogenesis. This study aims to describe the profile of potential fibrogenesis and inflammation genes that play a role in the progression of HCC due to chronic hepatitis C. This type of research is a descriptive study with a quantitative approach that was carried out using Quantitative Real-Time PCR analysis. The results of serological tests in the male gender group showed that the average fasting body glucose level was 85.22 mg/dL, total cholesterol 242 mg/dL, triglyceride 158.44 mg/dL, HDL-C 18.56 mg/dL, and LDL-C 172 mg/dL. In the female gender group, the data obtained on average levels of fasting blood glucose 82.33l mg.dL, total cholesterol 350 mg/dL, triglyceride 181 mg/dL, HDL-C 29 mg/dL, and LDL-C 190 mg/dL. All gender groups also showed an increase in AST and ALT levels that had exceeded normal limits. The expression of fibrosis-related genes, namely TGF-β1 was 5.8x higher in male patients than female patients. The NOX4 gene also showed almost the same thing, namely, its expression level was 1.2 times higher in male patients. From the expression of the proinflammatory cytokine TNF-, it is also known that in male patients, the expression level is 2x times higher than in female patients. The difference in expression levels in the two groups involved a repressive mechanism of estrogen. Increased expression levels of TGF-β1, NOX4, and TNF- genes are thought to involve the activity of the HCV core protein, which then induces several signaling pathways such as NF-κB and SMAD3. From these results, the expression levels of TGF-β1, NOX4, and TNF- as the main regulators of chronic inflammation and fibrosis can describe the progression of HCC and can be used as initial data on the profile of inflammation and fibrogenesis in HCC cases that have previously been exposed to HCV infection.

Incidence and Patterns of Liver Cancers in Sri Lanka from 2001 to 2010: Analysis of National Cancer Registry Data.

Sanjeewa SeneviratneObjectives Varying trends in the incidence of liver cancer have been observed in many Asian countries. We conducted this study to examine trends in liver cancer incidence and histological patterns in Sri Lanka. Materials and Methods All newly diagnosed patients with liver cancer included in Sri Lanka National Cancer Registry during 2001 to 2010 were analyzed. Statistical Analysis Joinpoint regression analysis was performed. A p -value of less than 0.05 was considered statistically significant. Results Overall, 1,482 (male:female = 2.7:1; mean age = 57.5 years) liver cancers were analyzed. Majority were hepatocellular carcinomas ( n = 1,169; 78.9%), followed by intrahepatic cholangiocarcinomas ( n = 100; 6.75%). Highest incidence of liver cancer was observed in 70-74-year age group (5.1/100,000). Overall, the World Health Organization age-standardized rate (ASR) has increased during 2001 to 2004, from 0.6/100,000 (95% confidence interval [CI] = 0.48-0.72) to 1.0/100,000 (95% CI = 0.85-1.15), with an estimated annual percentage change (EAPC) of 17.8 (95% CI = 5.0-46.2); p > 0.05. From 2004 to 2010, a gradual decline in the incidence was observed. ASR in 2010 was 0.96 (95% CI = 0.81-1.1), with an EAPC of -0.9 (95% CI = -6.7 to 5.4); p > 0.05. Similar patterns of incidence change were observed in both genders. Conclusions Overall, the incidence of liver cancer appears to be steadily declining in Sri Lanka. Similar patterns of incidence change were observed in both genders. The actual decline is likely to be greater as it is likely that diagnostic scrutiny and reporting would have improved during the study period.

Nonalcoholic fatty liver disease shows significant sex dimorphism.

Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.

Abstract PO-174: Using GIS mapping to explore factors in Texas' disparities in access to cancer care

Abstract Introduction: The significant decline in cancer incidence and mortality over the last two decades in the United States is likely the result of reductions in tobacco use, increased uptake of preventive methods, adoption of early screening methods and improved treatment options. Texas, due to its large size and significant rural and heterogeneous populations, continues to experience disparities in cancer incidence and access to care and clinical trials. This study aimed to: 1) assess cancer incidence in Texas for three target indications compared to national data, and 2) analyze potential disparities in access to care with respect to the locations of American College of Surgeons Accredited (ACoS) Cancer Centers and National Cancer Institute (NCI) Cancer Centers within Texas' 11 Public Health Regions (PHR). Methods: We used data from the Texas Cancer Registry and compared age-adjusted incidence for our three target indications (adult colon cancer in patients under 50 years of age, advanced cervical cancer, and advanced liver cancer) in the 11 PHR and the defined Border Region of Texas with national data from the US Surveillance, Epidemiology, and End Results Program (SEER). We used GIS mapping to locate the cancer centers in Texas' PHR. Results: Initial results indicate that all 11 Texas' PHR ranked higher than national averages for age-adjusted incidence of cervical and liver cancer. Further, incidence rates for adolescents and young adult colorectal cancer are above SEER average in the majority of the PHR located in the northern and eastern regions of the state. When compared with Texas incidence rates, PHR 1 (Lubbock) and PHR 11 (Harlingen) have higher incidence rates for all three indications. Two PHR in the Border region (PHR 10: El Paso and 11: Harlingen) have Texas' highest incidence of liver cancer. The distribution of ACoS centers appears concentrated in eastern Texas, with highest numbers in PHR 3 (Dallas area) and PHR 6 (Houston area); with three of the four NCI-designated cancer centers in Texas are located in these two regions. Lower rates of cancer incidence for all three cancer indications were found in PHR regions 3 and 6. Among the Border counties, Cameron, Maverick and Star counties ranked above the Texas' average for all three cancer indications. There is an apparent paucity of cancer centers in the Border Region with only three centers identified in the 32 counties within the region. Conclusion: Texas statewide ranked above SEER's averages in two of the three cancer indications-cervical and liver cancers. There are clear regional differences in incidence of cervical, liver, and colorectal cancer which suggest disparities in access to care. Future research will draw on these findings to assess distance to cancer centers and clinical trial locations for Texas patients in our three targeted cancers and determine if broadband coverage is associated with disparities in cancer rates. Citation Format: Yeka W. Nmadu, Deborah V. Dahlke, Scott A. Horel, Marcia G. Ory, Kenneth S. Ramos. Using GIS mapping to explore factors in Texas' disparities in access to cancer care [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-174.

Spatial epidemiologic analysis of the liver cancer and gallbladder cancer incidence and its determinants in South Korea

BackgroundThere have been reports on regional variation in prevalence of hepatitis B and C, and Clonorchis sinensis (C. sinensis) infection, which indicates potential of spatial variation in liver cancer and gallbladder cancer incidence in Korea. Therefore, we aimed to assess the regional variation of liver and gallbladder cancer incidence and its determinants based on the regional distribution of risk factors, including hepatitis B infection in Korea.MethodsThis study used an ecological study design and district-level cancer incidence statistics generated by the National Cancer Center. Spatial clusters of liver and gallbladder cancer incidence were detected based on spatial scan statistics using SaTScan™ software. We set the size of maximum spatial scanning window of 25 and 35% of the population at risk for analyses of liver and gallbladder cancer, respectively. Significance level of 0.05 was used to reject the null hypothesis of no cluster. We fitted the Besag-York-Mollie model using integrated nested Laplace approximations to assess factors that influence the regional variation in cancer incidence.ResultsSpatial clusters with high liver cancer incidence rates were detected in the southwestern and southeastern regions of Korea. High gallbladder cancer incidence rates are clustered in the southeastern region. Regional liver cancer incidence can be accounted for the prevalence of high household income (coefficient, − 0.10; 95% credible interval [CI], − 0.18 to − 0.02), marital status (coefficient, − 0.14; 95% CI, − 0.25 to − 0.03), the incidence of hepatitis B (coefficient, 0.87; 95% CI, 0.29 to 1.44), and liver cancer screening (coefficient, 0.06; 95% CI, 0.00 to 0.12), while gallbladder cancer incidence was related to the prevalence of high household income (coefficient, − 0.03; 95% CI, − 0.05 to 0.00) and living close to a river with a high prevalence of liver fluke infection (coefficient, 0.55; 95% CI, 0.14 to 0.96).ConclusionsThis study demonstrated geographic variation in liver and gallbladder cancer incidence, which can be explained by determinants such as hepatitis B, income, marital status, and living near a river.

Current Issues of Epidemiological Surveillance of Chronic Viral Hepatitis B, C, D and Hepatocellular Carcinoma at the Regional Level

Introduction. To achieve the goal of eliminating viral hepatitis by 2030, it is necessary to assess the real situation, improve epidemiological surveillance and prevention of these infections. Objectives: To evaluate the results of epidemiological surveillance of chronic viral hepatitis B, C, D and hepatocellular carcinoma in order to optimize the surveillance system at the regional level. Materials and methods: We analyzed the incidence of viral hepatitis B, C and liver cancer in the regions of the Northwestern and Central Federal Districts of the Russian Federation over the past 10 years. We also studied the prevalence of hepatitis B, C, D, and hepatitis C virus genotypes (6,020 cases), and examined 465 case histories of patients with hepatocellular carcinoma in the Leningrad Region using techniques of epidemiological analysis, ELISA, PCR, and statistical methods. Results: We established a tendency towards a decrease in the incidence of chronic hepatitis B and C in all study areas. In 2020, high rates of hepatitis B (26.2 and 9.1) and hepatitis C (49.2 and 39.2) were registered in St. Petersburg and Moscow per 100,000 population, respectively. The prevalence of hepatitis D in the Leningrad Region was 6.3 per 100,000 population. Hepatitis C virus genotypes 1 and 3 prevailed (48.9 % and 43.9 %, respectively). A high incidence of liver cancer was established in St. Petersburg, the Pskov and Novgorod Regions. Conclusions: Our findings prove the efficiency of the surveillance system and prevention of chronic hepatitis B and C. The main objectives are to further reduce the incidence rate, screen all patients with chronic hepatitis B for hepatitis D, and use the results of molecular genetic studies and cancer registries for epidemiological surveillance purposes.

Aflatoxin and the Etiology of Liver Cancer and Its Implications for Guatemala.

During the 60 years since the first scientific reports about a relation between aflatoxin exposure and adverse health consequences, both in animals and humans, there has been a remarkable number of basic, clinical and population science studies characterizing the impact of this mycotoxin on diseases such as liver cancer. Many of these human investigations to date have focused on populations residing in Asia and Africa due to the high incidence of liver cancer and high exposures to aflatoxin. These studies formed the basis for the International Agency for Research on Cancer to classify the aflatoxins as Group 1 known human carcinogens. In addition, aflatoxin contamination levels have been used in international commodity trade to set the price of various staples such as maize and groundnuts. While there have been many case-control and prospective cohort studies of liver cancer risk over the years there have been remarkably few investigations focused on liver cancer in Latin America. Our interdisciplinary and multiple institutional collaborative has been developing a long-term strategy to characterize the role of aflatoxin and other mycotoxins as health risk factors in Guatemala and neighboring countries. This paper summarizes a number of the investigations to date and provides a roadmap of our strategies for the near term to discern the emergent etiology of liver cancer in this region. With these data in hand public health-based prevention strategies could be strategically implemented and conducted to lower the impact of these mycotoxins on human health.

The Threat of Multiple Liver Carcinogens in the Population of Laos: A Review

Laos is a landlocked country in South East Asia, ranking fifth for primary liver cancer incidence worldwide. Risk factors that might explain this worrying situation are poorly known. We conducted a review of the literature concerning the etiologies of terminal liver diseases in Laos. A double infectious burden with hepatitis B and C viruses and the liver fluke Opisthorchis viverrini seems to be the main cause of the high liver cancer incidence. Moreover, it was also suggested that mutagenic substances frequently found in tobacco, alcoholic beverages, fermented fish, and mold-contaminated cereals or nuts, which are all substances heavily consumed by Lao people, lead to the accumulation of DNA mutations in the liver cell genome causing tumor processes. However, the respective proportions of liver cancer cases attributable to each category of infections and substances consumed, as well as the histological nature of the neoplasia are still not precisely documented in Laos. The international medical and scientific communities as well as public health stakeholders should urgently consider the alarming situation of liver health in Laos to stimulate both research and subsequent implementation of prevention policies.

Abstract 1626: A novel mouse model of hepatocellular carcinoma induced by c-myc overexpression

Abstract Hepatocellular carcinoma is a fatal liver cancer, and there are limited treatment options for this cancer. c-Myc is a key oncogene in liver cancer, but the specific mechanism of carcinogenesis in liver is unknown. Animal models are widely used to explore the molecular pathogenesis of HCC and test new drug candidates. In this poster, we reported a c-Myc conditional over-expression mouse model (LSL-Myc), which inserts the CAG-Loxp-stop-Loxp-c-Myc-polyA expression cassette into the H11 site. The expression of the Myc gene in this mouse model is regulated by Cre recombinase, which is not normally expressed, but only expressed in Cre-expressing tissue cells. LSL-Myc / Alb-cre double-positive mice were produced by crossing LSL-Myc hybrid mice with Alb-cre mice. In this mouse model, c-Myc was specifically expressed in liver cells. LSL-Myc / Alb-cre double-positive mice show a typical HCC phenotype and show accelerated tumor initiation and rapid HCC progression. Mice can detect significant liver tumorigenesis at 2 months of age, and 100% mice can occur hepatocellular carcinoma. The liver cancer tissues from LSL-Myc / Alb-cre double-positive mice can be transplanted to C57BL/6 mice to establish a mouse-derived PDX model. In summary, this model has the advantages of rapid oncogenesis and high incidence of liver cancer. It is an ideal model for studying the mechanism of c-Myc-driven liver cancer and c-Myc targeted therapy. Citation Format: Jinjin Wang, Dan Feng, Haiyan Zhu, Lei Ci, Zhipeng Wan, Ruilin Sun. A novel mouse model of hepatocellular carcinoma induced by c-myc overexpression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1626.

Abstract C003: A machine learning-based approach to identify biomarkers of environmental toxicant exposures relevant to liver cancer disparities in rural Illinois

Abstract Although there have been nationwide reductions in cancer death recently, liver cancer mortality remains a problem in rural Illinois. Research scientists anticipate that exposure to environmental toxicants in rural Illinois may be possible causes of increased liver cancer mortality in females. The purpose of our study is to identify potential biomarkers that are related to early liver toxicity through machine learning. We accessed gene expression data from the open source Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (TG-GATES) database from rats that had been exposed to over 170 toxicants relevant to liver cancer. We performed a differential gene expression analysis to identify significant features or genes that are related to hepatotoxicity endpoints (e.g., necrosis, centrilobular hypertrophy, and hepatocellular hypertrophy). Then we performed a feature selection method to decrease the dimensionality of the gene set. We then used classification modeling to identify specific genes related to our hepatotoxicity endpoints. Lastly, we built a predictive model by random splitting of the complete gene set by one of the endpoints and used the complete differentially expressed gene set to predict this particular endpoint. Our model predicted specific genes that were highly related to liver toxicant exposure. In the next phase of our studies, we will use these biomarkers to associate geospatial toxicant exposures with health effects in wild mice caught from areas with high liver cancer incidence in the state of Illinois. Our approach identifies biomarkers of potential environmental exposures from wildlife liver gene expression data and associates presence of such compounds in environment soil and water sources in counties with high liver cancer incidence. Citation Format: Brandi Patrice Smith, Zeynep Madak-Erdogan. A machine learning-based approach to identify biomarkers of environmental toxicant exposures relevant to liver cancer disparities in rural Illinois [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C003.

MicroRNA-101 modulates cisplatin chemoresistance in liver cancer cells via the DNA-PKcs signaling pathway.

Due to the high incidence of liver cancer, chemoradiotherapy and prognosis of liver cancer are a primary focus of medical research. microRNAs (miRNAs/miRs) serve crucial roles in resistance to chemotherapy and radiotherapy. The aim of the present study was to investigate the effects of miR-101 on the chemotherapeutic efficacy of cisplatin (CDDP) in liver cancer. First, human liver cancer cells (HepG2) were transfected with a miR-101 mimic or miR-101 inhibitor to bidirectionally regulate the expression of miR-101. Cell proliferation, apoptosis, intracellular reactive oxygen species and comet assay results indicated that the upregulation of miR-101 sensitized HepG2 cells to CDDP, and downregulation of miR-101 reduced chemosensitivity. A xenograft mouse model further confirmed that miR-101 overexpression increased CDDP sensitivity in liver cancer. Luciferase reporter and western blotting assays demonstrated that transfection of the miR-101 mimic markedly reduced activity of the DNA-dependent protein kinase catalytic subunit/protein kinase B/mammalian target of rapamycin (DNA-PKcs/Akt/mTOR) pathway and increased expression of apoptotic protein caspase 3, which is induced by CDDP treatment. By contrast, miR-101 inhibitors partially reversed these changes. Moreover, the miR-101 mimic suppressed activity of the nuclear factor-κB (NF-κB) pathway, leading to increased susceptibility of HepG2 cells to chemotherapeutic agents. In conclusion, miR-101 overexpression augmented cytotoxicity and reduced chemoresistance to CDDP in HepG2 cells, and this was associated with negative regulation of DNA-PKcs/Akt/NF-κB signaling.

Qidong: a crucible for studies on liver cancer etiology and prevention.

Qidong (Jiangsu, China) has been of interest to cancer epidemiologists and biologists because, until recently, it was an endemic area for liver cancer, having amongst the highest incidence rates in the world. The establishment of the Qidong Cancer Registry together with the Qidong Liver Cancer Institute in 1972 has charted the patterns of liver cancer incidence and mortality in a stable population throughout a period of enormous economic, social, and environmental changes as well as of improvements in health care delivery. Updated incidence trends in Qidong are described. Notably, the China age-standardized incidence rate for liver cancer has dropped by over 50% in the past several decades. Molecular epidemiologic and genomic deep sequencing studies have affirmed that infection with hepatitis B virus as well as dietary exposure to aflatoxins through contamination of dietary staples such as corn, and to microcystins – blue-green algal toxins found in ditch and pond water – were likely important etiologic factors that account for the high incidence of liver cancer in this region. Public health initiatives to facilitate universal vaccination of newborns against HBV and to improve drinking water sources in this rural area, as well as economic and social mandates serendipitously facilitating dietary diversity, have led to precipitous declines in exposures to these etiologic factors, concomitantly driving substantive declines in the liver cancer incidence seen now in Qidong. In this regard, Qidong serves as a template for the global impact that a package of intervention strategies may exert on cancer burden.

Liver Cancer Disparities in New York City: A Neighborhood View of Risk and Harm Reduction Factors.

Liver cancer is the fastest increasing cancer in the United States and is one of the leading causes of cancer-related death in New York City (NYC), with wide disparities among neighborhoods. The purpose of this cross-sectional study was to describe liver cancer incidence by neighborhood and examine its association with risk factors. This information can inform preventive and treatment interventions. Publicly available data were collected on adult NYC residents (n = 6,407,022). Age-adjusted data on liver and intrahepatic bile duct cancer came from the New York State Cancer Registry (1) (2007-2011 average annual incidence); and the NYC Vital Statistics Bureau (2015, mortality). Data on liver cancer risk factors (2012-2015) were sourced from the New York City Department of Health and Mental Hygiene: (1) Community Health Survey, (2) A1C registry, and (3) NYC Health Department Hepatitis surveillance data. They included prevalence of obesity, diabetes, diabetic control, alcohol-related hospitalizations or emergency department visits, hepatitis B and C rates, hepatitis B vaccine coverage, and injecting drug use. Liver cancer incidence in NYC was strongly associated with neighborhood poverty after adjusting for race/ethnicity (β = 0.0217, p = 0.013); and with infection risk scores (β = 0.0389, 95% CI = 0.0088-0.069, p = 0.011), particularly in the poorest neighborhoods (β = 0.1207, 95% CI = 0.0147-0.2267, p = 0.026). Some neighborhoods with high hepatitis rates do not have a proportionate number of hepatitis prevention services. High liver cancer incidence is strongly associated with infection risk factors in NYC. There are gaps in hepatitis prevention services like syringe exchange and vaccination that should be addressed. The role of alcohol and metabolic risk factors on liver cancer in NYC warrants further study.