Risk Of Primary Liver Cancer Research Articles

Association between serum iron status and primary liver cancer risk: a Mendelian randomization analysis.

BackgroundSerum iron status has been reported as associated with primary liver cancer (PLC) risk. However, whether iron status plays a role in the development of PLC remains inconclusive.MethodsGenetic summary statistics of the four biomarkers (serum iron, ferritin, transferrin saturation, and transferrin) of iron status and PLC were retrieved from two independent genome-wide association studies (GWAS) that had been performed in European populations. Two-sample univariate and multivariate Mendelian randomization (MR) analyses were conducted to determine the causal link between iron status and PLC risk.ResultsNo significant horizontal pleiotropy was detected for the four biomarkers according to the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test. No evidence of between-single nucleotide polymorphism (SNP) heterogeneity and directional pleiotropy was detected by the Cochran’s Q test and MR-Egger regression for serum iron, ferritin, and transferrin. For transferrin saturation, although no heterogeneity was detected, the directional pleiotropy was significant (P value for intercept of MR-Egger regression =0.033). Univariate MR estimates based on inverse variance weighting (IVW) method suggested that there was no causal link between serum iron [odds ratio (OR) =0.71, 95% confidence interval (CI): 0.45 to 1.11], ferritin (OR =0.56, 95% CI: 0.16 to 2.04), and transferrin (OR =0.91, 95% CI: 0.72 to 1.15) and PLC risk. We found a significant causal relationship between transferrin saturation and PLC risk (OR =0.45, 95% CI: 0.22 to 0.90), although this link was non-significant in multivariate MR analysis.ConclusionsThere might be no causal relationship between iron status and PLC risk. However, data from larger sample size and people with different ethnic background were needed to further validate our findings.

Total cholesterol, alanine aminotransferase and the risk of primary liver cancer: A population-based prospective study.

Previous studies have shown that serum total cholesterol (TC) and serum alanine aminotransferase (ALT) are associated with liver cancer risk. However, the common contribution of TC and normal-high ALT to primary liver cancer (PLC) has not been reported. We aim to assess the separate and joint effect of low TC level and normal-high ALT level on the risk of PLC, a large prospective cohort was conducted in our study.The participants were divided into 4 groups via the cross-matching method according to TC [low level (−)/non-low level (+)] and ALT [normal level (−)/normal-high level(+)] status, and using the lower quartile value of TC and the upper quartile value of ALT as a threshold, respectively. Incident PLC was confirmed by review of medical records. Cox proportional hazards regression models and interactive additive models were used to evaluate whether the joint effect of low TC level and normal-high ALT level is associated with the risk of PLC.During 1,248,895 person-years follow-up, 298 participants were diagnosed with PLC among 114,972 subjects. In male population, TC < 4.24 mmol/L was group “TC (−)”; TC ≥ 4.24 mmol/L was group “TC (+)”; ALT < 23 U/L was group “ALT (−)”: 33 U/L ≥ ALT ≥ 23 U/L was group “ALT (+)”. Compared with the group “TC (+)”, group “ALT (−)”, respectively, the adjusted hazard ratio (HR) and 95% confidence interval (95%CI) for PLC risk was 1.74 (1.36–2.25) in group “TC (−)” and 1.49 (1.15–1.94) in group “ALT (+)”. In combinatorial analysis, compared with group “TC (+) and ALT (−)”, the significant increased risk of PLC were observed in group “TC (+) and ALT (+)” (HR = 1.41; 95% confidence intervals [CI]: 1.02–1.95), group “TC (−) and ALT (−)” (HR = 1.67; 95%CI: 1.24–2.27) and group “TC (−) and ALT (+)” (HR = 2.72; 95%CI: 1.81–4.09), respectively. However, no statistical significance was found among female.The separate and joint effect of low TC level and normal-high ALT level was observed for PLC risk in males. When combined, individuals with coexistence of low TC level and normal-high ALT level significantly increase the risk of PLC.

Examining the gut-liver axis in liver cancer using organoid models.

The World Health Organization predicts that by 2030 liver cancer will cause 1 million deaths annually, thus becoming the third most lethal cancer worldwide. Hepatocellular carcinoma and cholangiocarcinoma are the two major primary cancer subtypes involving the liver. Both are often diagnosed late, and hence response to treatment and survival are poor. It is therefore of utmost importance to understand the mechanisms by which liver cancers initiate and progress. The causes of primary liver cancer are diverse, resulting primarily from obesity, chronic alcohol abuse or viral hepatitis. Importantly, both alcohol and high fat diet can promote intestinal permeability, enabling microbial translocation from the gut into the liver. As a result, these microbial antigens and metabolites exacerbate hepatic inflammation and fibrosis, increasing the risk of primary liver cancer. Organoids are primary, three-dimensional, stem cell derived liver models that can recapitulate many of the disease phenotypes observed in vivo. This review aims to summarize the advantages of organoid culture to examine the gut-liver axis with respect to cancer initiation and progression. In particular, the use of gut and liver organoid mono- and co-cultures together and with immune cell populations to best recapitulate disease mechanisms and develop therapeutic interventions.

Advances in the study of occult malignant tumor-related pyogenic liver abscesses in the digestive system

Pyogenic liver abscess (PLA) accompanied by occult malignant tumors is a rare kind of life-threatening disease. Studies have shown that it can predict the occurrence of cancer, especially hepatobiliary and colorectal cancer. The risk of combined occult primary liver cancer, cholangiocarcinoma, and gastrointestinal cancer is high in PLA patients. Malignant tumor-related PLA lacks specific symptoms and signs. The iodine concentration ratio between the energy spectrum CT lesions and normal liver tissue is of certain value in the differentiation of liver cancer and liver abscess. Computed tomography colonography has a dual role. It can screen patients with PLA for occult colorectal cancer and determine the treatment response of abscess lesions. Klebsiella pneumoniae and Escherichia coli is the main microorganism of PLA related to colorectal cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma. PLA treatment related to hepatobiliary malignant tumor has high complications and mortality, and poor prognosis. Most occult colorectal cancers are in the early stage, and their early detection and prognosis are better than those of PLA patients combined with hepatobiliary malignancies.

Magnesium intake is associated with a reduced risk of incident liver cancer, based on an analysis of the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort

Liver cancer incidence and mortality are escalating globally. Magnesium intake has been studied extensively in nonmalignant liver pathology, but the association between dietary intake of magnesium and primary liver malignancy has not been previously evaluated. We aimed to determine the association between total magnesium intake and primary liver cancer risk. Using the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study prospective cohort, we estimated the association between magnesium intake and the risk of incident primary liver cancer using Cox proportional hazard modeling adjusted for relevant confounders. Comprehensive stratified and sensitivity analyses were performed. During 6.4 million person-years of follow-up time, 1067 primary liver cancers occurred in 536,359 participants. Higher magnesium intake was independently associated with a lower risk of liver cancer (P-trend=0.005), with intakes in the highest compared with lowest quartile associated with 35% lower risk (HR: 0.65; 95% CI: 0.48, 0.87). The dose-related inverse association was more pronounced in moderate and heavy alcohol users (HR: 0.54; 95% CI: 0.35, 0.82; P-trend=0.006), and this interaction was statistically significant (P-interaction=0.04). Based on a prospective cohort analysis, we demonstrated that magnesium intake is associated with a lower risk of primary liver cancer, which was more pronounced among moderate and heavy alcohol users. Robust experimental and mechanistic data provide a biological basis to support these findings.

Guideline for stratified screening and surveillance of primary liver cancer(2020 Edition)

The age-adjusted incidence of primary liver cancer (PLC) has been declining in China. However, PLC cases in China account for 55% globally. The disease burden is still high and the 5-year survival rate was not improved significantly in the past two decades. This guideline outlines PLC screening in the risk populations, both in hospital and community. Liver cirrhosis and chronic hepatitis B are the main causes of PLC in China. For better PLC surveillance and screening in clinical practices, it is recommended to stratify population at the risk into 4 risk levels, namely, low-risk, intermediate-risk, high-risk, and extremely high-risk.The lifelong surveillance is suggested for those at the risk of PLC. The intervals and tools for surveillance and screening are recommended based on the risk levels. Abdominal ultrasonography combined with serum alpha-fetoprotein examination (routine surveillance) every 6 months is recommended for those at a high risk of PLC.Routine surveillance every 3 months and enhanced CT/MRI examination every 6-12 months are recommended for those at an extremely high risk of PLC. The surveillance interval can be extended every 1 year or longer for those at a low-risk or at an intermediate-risk of PLC, because their annual incidence of PLC is very low. The cost-effectiveness of these recommendations remains to be evaluated.

Fasting Blood Glucose, Cholesterol, and Risk of Primary Liver Cancer: The Kailuan Study.

PurposeThe influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in China was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated.Materials and MethodsOverall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or total cholesterol (TC) with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBG/non-hypocholesterolemia, elevated FBG/hypocholesterolemia, and normal FBG/non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model.ResultsDuring 1,134,843.68 person-years follow-up, a total of 388 PLC cases occurred. We found the elevated FBG and hypocholesterolemia increase the risk for PLC, respectively. Compared with the non-hypocholesterolemia/normal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (hazard artio [HR], 1.19; 95% confidence interval [CI], 0.88 to 1.62) and hypocholesterolemia/normal FBG group (HR, 1.53; 95% CI, 1.19 to 1.97), and in the hypocholesterolemia/elevated FBG group (HR, 3.16; 95% CI, 2.13 to 4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease.ConclusionElevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated.

Guideline for stratified screening and surveillance in patients with high risk of primary liver cancer (2020)

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Proton Pump Inhibitors and Primary Liver Cancer

During the last years proton pump inhibitors (PPIs), previously regarded as very safe drugs and allowed to be sold over the counter, have been reported to give side effects in many organ systems. However, most of these negative reports probably are due to residual confounding factors. In general, the side effects of PPIs are due to their biological effect in removing the biological effect of gastric juice that is killing microorganisms, and the secondary hypergastrinemia in an unsuccessful attempt to restore normal gastric acidity. Whereas the possibility that hypergastrinemia could predispose to gastric cancer has been permanently on the agenda since the introduction of PPIs, the removal of the important protective effect towards microbes has surprisingly only been focused on during the later years as a consequence of increased interest on the gut microbiome. PPI treatment affects the microbiome, and it exists one report describing increased risk of primary liver cancer due to PPI use. Changes in the gut microbiome have been shown to participate in the pathogenesis of chronic liver diseases caused by ethanol as well as obesity. In general, chronic liver diseases predispose to liver cancer. There are also rodent studies incriminating inhibition of gastric acid secretion in the pathogenesis of primary liver cancer. However, it must be concluded that presently the role of PPIs in the development of primary liver cancer seems weak.

A prospective follow-up study of the relationship between high-sensitivity C-reactive protein and primary liver cancer

BackgroundCompeting risk method has not been used in a large-scale prospective study to investigate whether increased levels of high-sensitivity C-reactive protein (hs-CRP) elevate the risk of primary liver cancer (PLC). Our study aims to prospectively investigate the relationship between hs-CRP and new-onset PLC.Methods and resultsNinety-five thousand seven hundred fifty-nine participants without the diagnosis of PLC, and who had their demographic characteristics and biochemical parameters recorded, were analyzed from the Kailuan Cohort study. Cox proportional hazards regression models and competing risk regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of PLC. During a median follow-up of 11.07 years, 357 incidental PLC cases were identified over a total of 1,035,039 person-years. The multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.07(0.82 ~ 1.38), 1.51(1.15 ~ 1.98) in a Cox proportional hazard regression analysis adjusted for other potential confounders. In the cause-specific hazard model, the multivariable HRs (95%CI) for the association of hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L with PLC were 1.06(0.81 ~ 1.40), 1.50(1.14 ~ 1.99). Similar results were also observed in the sub-distribution hazard function model with corresponding multivariate HRs (95%CI) of 1.05(0.80 ~ 1.40), 1.49(1.13 ~ 1.98) in hs-CRP of 1–3 mg/L group and hs-CRP>3 mg/L group, respectively.ConclusionsThis prospective study found a significant association of higher levels of hs-CRP with new-onset PLC. The main clinical implications would be an increased awareness of hs-CRP and its correlation to the risk of PLC. This study should be a steppingstone to further research on chronic inflammation and PLC.Trial registrationRegistration number:ChiCTR–TNRC–11001489.

Obesity and the risk of primary liver cancer: A systematic review and meta-analysis.

Background/AimsIn this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer.MethodsThis study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included.ResultsA total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancer-related mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I2=80%).ConclusionsHigh BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.

Wilson disease, ABCC2 c.3972C > T polymorphism and primary liver cancers: suggestions from a familial cluster

BackgroundPolymorphisms in genes modulating xenobiotics metabolism, in particular the ABCC2 c.3972C > T single nucleotide polymorphism (SNP) at exon 28, have been suggested to increase primary liver cancer (PLC) risk. Conversely, the occurrence of PLCs in Wilson disease patients is a rare event, in contrast with the occurrence observed in other chronic liver diseases. Here we report the clinical case of five siblings carrying the ABCC2 c.3972C > T SNP; three of them were affected by Wilson disease and two brothers with Wilson disease also developed PLCs.MethodsThe presence of the ABCC2 c.3972C > T SNP was assessed by Sanger sequencing and the exposure of PLC risk factors by standardized questionnaires.ResultsNotably, PLCs occurred only in the two brothers with the ABCC2 c.3972C > T SNP and Wilson disease who resulted exposed to asbestos and cigarette smoking, but not in the other siblings with the ABCC2 c.3972C > T SNP, alone or in association with Wilson disease, not exposed to these carcinogens and/or to other known risk factors for PLCs.ConclusionsThese findings suggest that ABCC2 c.3972C > T SNP and WD, also in association, may not represent a sufficient condition for PLC development, but that co-occurrence of further host/exogenous risk factors are needed to drive this process, reinforcing the notion that liver carcinogenesis is the result of a complex interplay between environmental and host genetic determinants. Due to the sporadic cases of this study and the paucity of data currently available in literature on this issue, future investigations in a larger population are needed to confirm our findings.

Independent and Joint Associations between Serum Calcium, 25-Hydroxy Vitamin D, and the Risk of Primary Liver Cancer: A Prospective Nested Case–Control Study

Accumulating evidence has shown that serum calcium and vitamin D may be associated with or influence various cancer risks. However, no prospective studies have evaluated the independent and joint associations between prediagnostic levels of serum calcium and vitamin D and future risk of incident primary liver cancer. We used a nested case-control design to evaluate subjects over 22 years of follow-up. Serum calcium, 25-hydroxy vitamin D [25(OH)D], and three markers of hepatitis B virus and hepatitis C virus were measured in baseline serum from 226 incident primary liver cancer cases and 1,061 matched controls. We calculated ORs and 95% confidence intervals (CI) using logistic regression to estimate the associations between calcium, 25(OH)D, and primary liver cancer risk. Multivariable adjusted models showed that subjects with both low (ORLow/Medium = 1.48, 95% CI = 1.01-2.17) or high (ORHigh/Medium = 1.92, 95% CI = 1.34-2.76) calcium had an increased primary liver cancer risk, while those with high 25(OH)D had a decreased risk of primary liver cancer (ORHigh/Medium = 0.54, 95% CI = 0.35-0.82). In joint analyses, when compared with subjects with medium calcium and 25(OH)D, subjects with high calcium and medium 25(OH)D had elevated odds of developing primary liver cancer (OR = 1.89, 95% CI = 1.17-3.05); those with medium calcium and high 25(OH)D had reduced odds of developing primary liver cancer (OR = 0.34, 95% CI = 0.17-0.67); and subjects in other classifications of calcium and serum 25(OH)D levels had no change in the odds of developing primary liver cancer (all P > 0.05). In a nutrient-deficient population, we found that serum calcium and serum 25(OH)D could potentially be modifiable risk or protective factors. Our findings provide potential targets for primary liver cancer prevention and control.

Risk of primary liver cancer associated with gallstones and cholecystectomy: A competing risks analysis.

Previous research has revealed a positive relationship between GSD, cholecystectomy and primary liver cancer (PLC). However, previous studies had several limitations including the retrospective design, narrow assessment of potential confounders and lack of competing risk models in time-to-event analyses. We conducted a large prospective cohort study to explore the relationship between GSD, cholecystectomy and PLC. A total of 95,021 participants who had not been diagnosed with PLC previously were enrolled from the Kailuan Cohort study. Demographic characteristics and biochemical parameters were recorded at baseline for all participants. We used Cox regression models and competing risk regression models to evaluate the association of GSD and cholecystectomy with the risk PLC. A total of 306 incidental PLC cases were identified during a median follow-up of 9.05 (8.75–9.22) years per participant. Compared with the normal group, the multivariable HRs (95%CI) for the association of GSD and cholecystectomy with PLC were 1.77 (1.05–2.94), 5.25 (1.95–14.17). In the CS model, the multivariable HRs (95%CI) was 1.76 (1.05–2.94) for the association of GSD and cholecystectomy with PLC and 5.25 (1.95–14.17) for GSD and cholecystectomy. Similar results were also obtained in the SD model with corresponding multivariate HRs (95%CI) of 1.75 (1.01–3.00), 5.22 (1.90–14.07) in the GSD group and cholecystectomy group, respectively. GSD and cholecystectomy were associated with an elevated risk of PLC.Registration number: ChiCTR–TNRC–11001489.

Total cholesterol and the risk of primary liver cancer in Chinese males: a prospective cohort study

Objective: To investigate the association between total cholesterol (TC) and primary liver cancer in Chinese males. Methods: Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history and TC levels was collected at the baseline interview, as well as information on newly-diagnosed primary liver cancer cases during the follow-up period. A total of 110 612 males were recruited in the cohort by 31 December 2015. TC levels were divided into four categories by quartile (<4.27, 4.27-4.90, 4.90-5.56 and ≥5.56 mmol/L), with the first quartile group serving as the referent category. Cox proportional hazards regression model was used to evaluate the association between TC levels and primary liver cancer risk. Results: By December 31, 2015, a follow-up of 861 711.45 person-years was made with a median follow-up period of 8.83 years. During the follow-up, 355 primary liver cancer cases were identified. Compared with the first quartile, the HR of incident primary liver cancer among participants with the second, third and highest quartile TC levels were 0.76 (95%CI: 0.58-1.01), 0.59 (95%CI: 0.43-0.79), and 0.36 (95%CI: 0.25-0.52), respectively after adjusting for age, educational level, income level, smoking status, drinking status, body mass index, and HBsAg status (Pfor trend<0.001). Subgroup analyses found that the association between TC levels and primary liver cancer was robust (all Pfor trend<0.05). The results didn't change significantly after exclusion of newly-diagnosed cases within the first 2 years, males with history of cirrhosis or subjects who took antihyperlipidemic drugs, participants with higher TC levels had a lower risk of primary liver cancer (all Pfor trend<0.05) and HR(95%CI) of incident primary liver cancer among participants with the highest quartile TC levels were 0.41 (0.28-0.61), 0.36 (0.25-0.53) and 0.38 (0.26-0.54), respectively. Conslusion: In this large prospective study, we found that baseline TC levels were inversely associated with primary liver cancer risk, and low TC level might increase the risk of primary liver cancer.

Perceived dietary salt intake and the risk of primary liver cancer: a population-based prospective study.

Although a high-salt diet is associated with high risk of chronic diseases such as hypertension, stroke and cardiovascular disease, little is known about the relationship between a high-salt diet and the risk of primary liver cancer (PLC). Consequently, we prospectively assessed the association of high perceived salt intake with the risk of PLC in the Kailuan Study. In total, 97006 participants who were healthy adults or free living adults at the baseline (2006) were included in the present study. The data of perceived salt intake were collected via questionnaire and classified into three categories: <6g day-1 for low salt intake, 6-10g day-1 for intermediate salt intake, >10g day-1 for high-salt intake. PLC including hepatocellular carcinoma and intrahepatic cholangiocarcinoma (excluding liver metastasis), and was confirmed by review of medical records. We used a Cox proportional hazards model to analyse the association between high perceived salt diet and the risk of PLC after adjusting for possible confounders, including age, gender, body mass index, high sensitivity-C-reactive protein, low-density lipoprotein-cholesterol, total cholesterol, triglycerides, alanine aminotransferase, HbsAg positive, cirrhosis, fatty liver, hypertension, diabetes, drinking status, smoking status and physical exercise. During the follow-up period of 1113816person-years, 397 PLC events were diagnosed. After adjusting for most potential confounders, subjects in intermediate salt intake and high salt intake had a multivariable hazard ratio and 95% confidence interval of 1.49 (0.97-2.29) and 1.98 (1.22-3.22) (P for trend=0.0042), respectively, compared to low salt intake. A higher perceived salt intake was associated with a higher risk of PLC.

Mycotoxin exposure and human cancer risk: A systematic review of epidemiological studies.

In recent years, there has been an increasing interest in investigating the carcinogenicity of mycotoxins in humans. This systematic review aims to provide an overview of data linking exposure to different mycotoxins with human cancer risk. Publications (2019 and earlier) of case-control or longitudinal cohort studies were identified in PubMed and EMBASE. These articles were then screened by independent reviewers and their quality was assessed according to the Newcastle-Ottawa scale. Animal, cross-sectional, and molecular studies satisfied criteria for exclusion. In total, 14 articles were included: 13 case-control studies and 1 longitudinal cohort study. Included articles focused on associations of mycotoxin exposure with primary liver, breast, and cervical cancer. Overall, a positive association between the consumption of aflatoxin-contaminated foods and primary liver cancer risk was verified. Two case-control studies in Africa investigated the relationship between zearalenone and its metabolites and breast cancer risk, though conflicting results were reported. Two case-control studies investigated the association between hepatocellular carcinoma and fumonisin B1 exposure, but no significant associations were observed. This systematic review incorporates several clear observations of dose-dependent associations between aflatoxins and liver cancer risk, in keeping with IARC Monograph conclusions. Only few human epidemiological studies investigated the associations between mycotoxin exposures and cancer risk. To close this gap, more in-depth research is needed to unravel evidence for other common mycotoxins, such as deoxynivalenol and ochratoxin A. The link between mycotoxin exposures and cancer risk has mainly been established in experimental studies, and needs to be confirmed in human epidemiological studies to support the evidence-based public health strategies.

Hepatitis C Virus Infection and the Temporal Trends in the Risk of Liver Cancer: A National Register-Based Cohort Study in Sweden.

In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims of this study were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV infection between 1990 and 2015. The HCV cohort (n = 52,853) was compared with a matched non-HCV comparison cohort (n = 523,649). Both the national Cancer Register (CR) and Cause of Death Register (DR) were used for follow-up. The crude and age-standardized PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as HRs using stratified Cox hazards regression. There were 1,609 with PLC diagnosis in the HCV cohort; the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013 while remaining low and stable in the comparison cohort. In the HCV cohort, the age-standardized PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 [95% confidence interval (CI), 1.54-3.75] in 2000 and 3.31 (2.51-4.12) in 2014. The highest SIR was 73 (65.9-79.5) among those infected for 35 to 40 years; and the highest HR was 65.9 (55.9-77.6) for men and 62.2 (31.9-121.1) for women. There was a considerable increase in PLC incidence over time and an extremely high relative risk in the population with HCV infection for more than 35 years. The national HCV-associated PLC incidence should be monitored in future studies to evaluate the effect of direct-acting antiviral (DAA) treatment.

Abdominal and gluteofemoral size and risk of liver cancer: The liver cancer pooling project.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to <25 kg/m2 ; HR = 1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR = 1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR = 0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements.

Herbal Medicine Containing Aristolochic Acid and the Risk of Primary Liver Cancer in Patients with Hepatitis C Virus Infection.

We investigated the association between taking herbal medicine (HM) containing aristolochic acid (AA) and the risk of primary liver cancer (PLC) among patients with hepatitis C virus (HCV) infection. This is a prospective study for the long-term follow-up of a nationwide population-based cohort of patients ages 18 years or older diagnosed with HCV infection during 1997 to 2010. A total of 223,467 HCV-infected patients were identified using the National Health Insurance Research Database in Taiwan. The use of HM containing AA was evaluated among patients who had visited traditional Chinese medicine clinics beginning from 1997 to 1 year prior to the diagnosis of PLC or dates censored (2003). We tracked each individual patient from 1997 to 2013 to identify incident cases of PLC since 1999. During the follow-up period of 3,052,132 person-years, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 person-years. The adjusted HRs were 1.21 [95% confidence interval (CI), 1.18-1.24], 1.48 (95% CI, 1.37-1.59), 1.50 (95% CI, 1.34-1.68), and 1.88 (95% CI, 1.61-2.19) for estimated AA usage groups: 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure (reference group). The current findings suggest that among HCV-positive patients, increasing exposure to AA poses an increased risk of acquiring PLC. AA may increase the risk of PLC in HCV-positive populations.