Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Understanding the genetic basis for cholangiocarcinoma.

Cholangiocarcinoma is associated with several different risk factors, many of which have known genetic associations. Advances in our understanding of the human genome have translated to the development of gene specific and whole genome assays for identifying gene variants and other alterations associated with cancer development. An improved understanding of the inherited genetic variants associated with risk of cholangiocarcinoma has the potential to improve our understanding of the basic biology of cholangiocarcinoma, enhance the performance of risk stratification models for identifying individuals at highest risk for cholangiocarcinoma, and identifying genetic variants associated with predisposition to cholangiocarcinoma in families with multiple affected individuals. It is increasingly recognized that major cancer-causing mutations or other gene alterations associated with familial risk of multiple cancers can also occur as germline events in individuals with apparently sporadically occurring cancer. In this chapter we review the major risk factors for cholangiocarcinoma as well as known gene variants associated with these risk factors, gene variants that have been associated with cholangiocarcinoma as the result of interrogation of candidate genes known to be associated with putative cancer causing pathways in cholangiocarcinoma, as well as the prevalence of major cancer causing genetic aberrations shown to be inherited in the germline of patients with sporadically developed cholangiocarcinoma. There has not yet been any large-scale genome wide association study of cholangiocarcinoma, and the results from such a study are eagerly anticipated.

Hepatitis B Screening of At-Risk Immigrants Seen at Primary Care Clinics: A Quality Improvement Project.

OBJECTIVE: To test an intervention to increase screening for hepatitis B (HBV) in at-risk immigrants in the primary care setting. PATIENTS AND METHODS: From a Mayo Clinic primary care panel, we identified approximately 19,000 immigrant patients from 9 high-risk countries/ethnic groups with intermediate or high prevalences of chronic HBV. Eligible patients with no record of prior HBV testing scheduled for primary care visits within the study period spanning October 1, 2017, through October 31, 2018, were identified. During the intervention period, the primary health care professional was notified by email 1 week prior to each primary care visit and encouraged to discuss screening for HBV infection and order screening tests at the appointment. We assessed rates of HBV screening during control and intervention periods. RESULTS: We identified 597 patients in the control period and 212 patients in the intervention period who had not been screened previously for HBV. During the intervention period, 31.4% (58) of the 185 eligible patients were screened for HBV vs 7.2% (43) of the 597 eligible patients in the control period. Thus, the intervention resulted in a 4.3-fold increase in screening (P<.00001). Of the 101 patients screened in the at-risk population, 22 (21.8%) screened positive for prior exposure to HBV (hepatitis B core antibody-positive) and 6 (5.9%) for chronic HBV infection (hepatitis B surface antigen-positive). CONCLUSION: Notifying primary care physicians of the high-risk status of immigrant patients substantially increased screening for HBV. Identifying patients with HBV is important for monitoring disease prevalence, preventing transmission, and initiating treatment and cancer surveillance, allowing earlier recognition and prevention of chronic hepatitis, disease reactivation, cirrhosis, and hepatocellular carcinoma.

Gallbladder cancer: epidemiology and genetic risk associations.

Gallbladder cancer (GBC) is a form of hepatobiliary malignancy that develops from the mucosal lining of the gallbladder. The early development of gallbladder cancer is usually asymptomatic and gallbladder cancer has a high propensity to metastatic dissemination, thus most patients are diagnosed at intermediate to advanced stages for which there is no curative treatment. Consequently, gallbladder cancer is highly lethal. Though the overall global incidence of gallbladder cancer is low, there is marked geographic variation and ethnic communities in Asia as well as Native American populations in both North and South America are affected disproportionately. This article provides a comprehensive overview of the current epidemiology and risk and protective factors associated with gallbladder cancer development. In addition, the current knowledge on environmental and genetic risk associations for gallbladder cancer and the need for additional large-scale genome wide association studies (GWAS) are discussed.