Search

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.

Introduction: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data have suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs is yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. Methods: We prospectively collected data and serum samples from 767 HCC patients treated at the University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% confidence interval [CI]: 52.5, 83.3). Biomarker association with OS was evaluated by the log-rank method. Results: The median OS in this cohort was 14.2 months (95% CI: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. Conclusion: Our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinoma (ACC) is a rare malignancy whose risk factors are unclear. We explored the association of ACC risk with exposure to selected environmental factors, with a focus on cigarette smoking. We conducted a hospital‐based case–control study at The University of Texas MD Anderson Cancer Center. Cases (n = 432) patients with ACC treated at MD Anderson, and controls (n = 1,204) were healthy and genetically unrelated spouses of patients at MD Anderson who had cancers not associated with smoking. Information on the subjects' demographic features and selected risk factors was collected using a structured, validated questionnaire and medical records review. Unconditional logistic regression was used to calculate adjusted odds ratios (AORs) via the maximum‐likelihood method. Cases had a younger mean (± standard deviation) age than did controls (47.0 ± 0.7 and 60.0 ± 0.3 years, respectively), and the majority of cases were female (60.6%) and non‐Hispanic white (82.4%). We found a markedly increased risk of ACC among male cigarette smokers, with an AOR = 1.8 (95% confidence interval [CI] =1.2–2.9), but not among female smokers (AOR = 1.1, 95% CI = 0.7–1.6). Family history of cancer was associated with increased risk of ACC (AOR = 2.8, 95% CI 1.9–4.3) and in both men and women, whereas alcohol consumption was associated with reduced risk in men (AOR = 0.2, 95% CI = 0.1–0.3) but not women (AOR = 0.7, 95% CI = 0.5–1.1). Understanding these risk factors and their underlying mechanisms may help prevent ACC in susceptible individuals and eventually identify new therapeutic options for ACC. What's new? Adrenocortical carcinoma (ACC) is a rare malignancy that generally is sporadic in nature. In addition, little is known about ACC risk factors, complicating its diagnosis and treatment. In this study, environmental factors, including cigarette smoking, were investigated for potential links to ACC risk. Retrospective analysis of a large cohort ACC patients and control subjects reveals an increased risk of ACC in male smokers and in male and female individuals with family history of malignancy. History of alcohol use was associated with reduced ACC risk in men. Further investigation of these risk factors could lead to novel ACC prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC., Methods: We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions., Results: The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015)., Conclusion: Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate., Competing Interests: Conflict of Interest: Dan G. Duda received consultant fees from Innocoll and research grants from Bayer, Surface Oncology, Exelixis, and BMS. No funding or reagents from these companies were used in this study. All other authors report no commercial associations (e.g., consultancies, stock ownership, equity interests, or patent-licensing arrangements) that might pose a conflict of interest in connection with the submitted article.

Background: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course., Case Description: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a fever of 39.0 ℃ 10 days after therapy initiation. He presented 5 days later with persistent fever as well as a headache, vomiting, chills, generalized pain, fatigue, mild abdominal discomfort, and a burning rash present on his neck and face. Complete blood counts showed severe neutropenia [absolute neutrophil count (ANC) of 90 cells/µL], leukopenia [white blood cell (WBC) count 500 cells/µL], thrombocytopenia [platelet count (PC) 18,000 cells/µL], and mild anemia (hemoglobin level 12.6 gm/dL). Imaging findings showed colitis on computed tomography (CT). Atezo/bev therapy was discontinued. Treatment plan constituted of cefepime and filgrastim, a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia, metronidazole for colitis, and intravenous methylprednisolone for immune-related toxicities. The patient fully recovered after 4 days of admission., Conclusions: In conclusion, we observed temporary severe febrile neutropenia and pancytopenia during systemic immunotherapy in a patient with unresectable HCC. Healthcare providers should consider hematological irAEs (hem-irAEs) in patients after the administration of ICIs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-290/coif). A.O.K. reports that he received the NCI SPORE grant (No. NCI R01, CA260872-01). The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)