Higher Risk Of Liver Cancer Research Articles

Risk of Malignancy in Indeterminate Liver Nodules Among Patients with Cirrhosis: A Retrospective Cohort Study

BackgroundSeveral studies have shown a higher risk of liver cancer from indeterminate liver nodules, but the exact occurrence and predictors of liver cancer in this group are still unclear. Our aim is to study the development of liver cancer in this population and identify any potential risk factors.MethodsThis retrospective study evaluated cirrhotic patients with indeterminate liver nodules from 2013 to 2023.Data from electronic patient records was analyzed to assess the association between HCC and baseline factors. Subgroup exploratory analysis compared characteristics of patients with de novo HCC and those with nodule transformation HCC.ResultsOut of 116 patients with liver nodules, 19 (16%) developed HCC in up to 7.5-year follow-up. Univariate Cox regression analysis showed a significant association between HCC incidence and smoking [hazard ratio (HR) 2.60, 95% Confidence Interval [CI] 1.01–6.74), nodule diameter exceeding 2 cm (HR 5.41, 95% CI 1.45–20.18), and baseline LI-RADS score 3 (HR 3.78, 95% CI 1.36–19.52). Multivariate Cox regression analysis revealed significant independent associations with nodule diameters 1 cm to < 2 cm (adjusted HR 3.35, 95% CI 1.06–10.60) and greater than 2 cm (adjusted HR 5.85, 95% CI 1.10–31.16), as well as with LI-RADS 3 lesions (adjusted HR 3.75, 95% CI 1.16–12.11) with adjusting other potential predictors and covariates.ConclusionOur findings show a higher incidence of HCC in patients with indeterminate liver nodules, increasing over time and reaching 30% at seven years. Nodules larger than 1–2 cm or LI-RADS 3 lesions pose increased risk for HCC. Enhanced surveillance is necessary given the lack of clear management guidelines.

Ultra-processed products and risk of liver cancer: A prospective cohort study

Background & AimsSeveral studies have shown positive associations between ultra-processed foods and drinks and cancer risk. However, evidence remains limited for liver cancer. We aimed to evaluate the associations between ultra-processed foods and drinks and liver cancer risk. MethodsWe included 73,119 participants (22,431 Whites, 47,837 Blacks, 2851 other race) from the Southern Community Cohort Study. Ultra-processed products were defined based on the Nova classification using data from a validated food frequency questionnaire and calculated as percentage of daily foods by weight. Incident liver cancer and vital status were ascertained via linkages to state cancer registries and the National Death Index as of December 31, 2019. ResultsWith a median of 13.9 year’s follow-up, we documented 453 incident liver cancer cases. Participants with higher intake of ultra-processed foods had an elevated risk of liver cancer (hazard ratios [HR] Tertile 3 vs. tertile 1 1.69, 95% confidence intervals [CI]: 1.28-2.22; Ptrend<0.001). The subclasses of ultra-processed foods, such as ultra-processed grains and fried potatoes (HR T3 vs. T1 1.29, 95% CI: 1.01-1.65; Ptrend=0.03), processed protein foods (HR T3 vs. T1 1.49, 95% CI: 1.14-1.94; Ptrend=0.007) and mixed dishes (HR T3 vs. T1 1.39, 95% CI: 1.09-1.77; Ptrend=0.01), were positively associated with liver cancer risk. No significant association was found for ultra-processed drinks (HR T3 vs. T1 0.85, 95% CI: 0.67-1.07; Ptrend=0.16). DiscussionIn a prospective cohort with predominantly low-income Southern US adults, we found certain ultra-processed foods were associated with a higher risk of liver cancer. Further studies are needed to confirm our findings.

Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: a Mendelian randomization study.

Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations. We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota. Independent genetic instruments linked with iron status were selected using a genome-wide threshold of p = 5 × 10-6 from corresponding genome-wide association studies. Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia. Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer. Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases. This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

Combined effects of smoking and alcohol consumption on the risk of liver cancer according to metabolic syndrome: A nested case-control study in South Korea.

Tobacco and alcohol may interact to increase the risk of liver cancer, which might be modified by other risk factors. Their combined effects in the context of metabolic syndrome (MetS) remain unclear. Given the increasing prevalence of MetS, this nested case-control study was conducted to evaluate the combined effects of smoking and alcohol consumption on liver cancer risk with stratification by MetS. We included 15,352 liver cancer patients and 92,112 matched controls who attended the nationwide general health examination during 2009-2019, using a customized database (N = 5,545,835) from the Korean National Health Insurance Service. Liver cancer risk according to smoking and alcohol consumption was estimated using conditional multivariable logistic regression. Additive and multiplicative interactions between these two factors were assessed. Results showed that in men, dual current users were at a significantly higher risk of liver cancer compared with dual nonusers, adjusted odds ratio (aOR) = 1.61, 95% confidence interval: (1.50, 1.72). Interactions were detected between light-to-moderate alcohol consumption (0.1-28 g/day) and heavy smoking (>20 pack-years) on additive scale, relative excess risk due to interaction = 0.34 (0.16, 0.51), attributable proportion = 0.22 (0.11, 0.33), synergy index = 2.75 (1.85, 3.66), and multiplicative scale, aOR for the product term = 1.28 (1.11, 1.49). An additive interaction was also revealed between light-to-moderate drinking and light-to-moderate smoking in the MetS subgroup. In women, light-to-moderate drinking/nonsmoking was negatively associated with the risk in the non-MetS subgroup. In conclusion, a holistic health promotion program should target male dual users of tobacco cigarettes and alcohol, including light-to-moderate users, especially those with MetS.

Abstract 3434: Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank

Abstract Introduction: The association between adiposity and cancer risk differs between sexes for some cancer types. Methods: We prospectively examined adiposity in relation to cancer incidence according to sex hormones in the UK Biobank. Adiposity was assessed by body mass index (BMI) and visceral adipose tissue (VAT), the latter predicted using determinants of age, height, weight, hip circumference, waist circumference, and race. Serum sex hormone binding globulin (SHBG), testosterone, and estradiol were measured using a biochemistry assay and were classified as high or low based on median levels. Cancer incidence was ascertained using ICD-10 codes through cancer registry linkage. For cancer types showing a sex difference in the association between adiposity and cancer incidence, we assessed multiplicative and additive interaction with sex hormones in men and women separately and corrected for multiple testing using false discovery rate. We used Cox regression to calculate the multivariable hazard ratio (HR) of cancer per increase between the 90th to 10th percentile of adiposity (BMI or predicted VAT). Results: During a median follow-up of 13.1 years, we documented 23,964 and 21,045 incident cancer cases among 217,460 men and 256,163 women, respectively. Adiposity showed a much stronger association with higher risk of colorectal, esophageal, and liver cancers in men than women. In men, BMI was more strongly associated with higher risk of colorectal cancer in low vs. high levels of SHBG (HR (95%CI) of 1.47 (1.31-1.64) vs. 1.12 (0.94-1.33) (adjusted Pinteraction = 0.027). In contrast, BMI showed a stronger association in high vs. low levels of SHBG with esophageal (HR = 2.39 vs. 1.62) and liver cancers (HR = 3.24 vs 1.96) in men (adjusted Pinteraction = 0.038 and 0.027, respectively). Among women, BMI was associated with a higher risk of esophageal cancer in those with low SHBG (HR=1.68) but not in those with high SHBG (HR=0.64) (adjusted Pinteraction = 0.025). Similar patterns were observed for predicted VAT. Men with high SHBG levels and high adiposity (BMI and predicted VAT) had 7.63 (5.08-11.46) and 8.92 (5.72 to 13.90), respectively, times higher risk of liver cancer compared to men with low SHBG levels and low adiposity. No effect modification by estradiol or testosterone was detected for any of the cancers studied. Conclusions: The association between adiposity and colorectal, esophageal, and liver cancer differed by sex. SHBG may be an important factor underlying these differences. Citation Format: LeeAnn Lucas, Yujia Lu, Edward L. Giovannucci, Mingyang Song. Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3434.

A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men.

Dietary factors have been extensively investigated as possible risk factors for liver cancer, but the evidence is inconclusive. Our study systematically assessed the association between 142 foods and nutrients and liver cancer risk in a Chinese population using a diet-wide association study. Based on data from 59,844 men in the Shanghai Men's Health Study (SMHS), we assessed the diet intake by dietary questionnaires. Cox regression was used to quantify the association between each food and nutrient and liver cancer risk. A false discovery rate (FDR) of 0.05 was used to select the foods and nutrients for validation. In the cohort, 431 liver cancer cases were identified during 712,373 person-years of follow-up. Retinol (HR per 1 SD increment = 1.09, 95% CI: 1.03-1.14) was associated with a higher risk of liver cancer, whereas onions (HR per 1 SD increment = 0.67, 95% CI: 0.54-0.84) and manganese (HR per 1 SD increment = 0.85, 95% CI: 0.78-0.94) were inversely associated with liver cancer risk. In the replication analysis, estimates for these foods and nutrients were similar in magnitude and direction. Our findings confirm that retinol, onions and manganese were associated with liver cancer risk, which provides reliable evidence between diet and liver cancer development.

Regular use of paracetamol and risk of liver cancer: a prospective cohort study

BackgroundParacetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer.MethodsThis prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up.ResultsDuring a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06–1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up.ConclusionThe regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

Helicobacter hepaticus and Helicobacter bilis in liver and biliary cancers from ATBC and PLCO.

Helicobacter species (spp.) have been detected in human bile and hepatobiliary tissue Helicobacter spp. promote gallstone formation and hepatobiliary tumors in laboratory studies, though it remains unclear whether Helicobacter spp. contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to Helicobacter (H.) hepaticus or H. bilis proteins was associated with the development of hepatobiliary cancers in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, and US-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). We included 62 biliary and 121 liver cancers, and 190 age-matched controls from ATBC and 74 biliary and 105 liver cancers, and 364 age- and sex-matched controls from PLCO. Seropositivity to 14 H. hepaticus and H. bilis antigens was measured using a multiplex assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major hepatobiliary cancer risk factors and Helicobacter pylori serostatus. Seropositivity to the H. bilis antigen, P167D, was associated with more than a twofold higher risk of liver cancer (OR: 2.38; 95% CI: 1.06, 5.36) and seropositivity to the H. hepaticus antigens HH0407 or HH1201, or H. bilis antigen, HRAG 01470 were associated with higher risk of biliary cancer (OR: 5.01; 95% CI: 1.53, 16.40; OR: 2.40; 95% CI: 1.00, 5.76; OR: 3.27; 95% CI: 1.14, 9.34, respectively) within PLCO. No associations for any of the H. hepaticus or H. bilis antigens were noted for liver or biliary cancers within ATBC. Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers.

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.

Association of dietary insulinemic and inflammatory potential with risk of liver cancer and chronic liver disease mortality in postmenopausal women: a prospective cohort study

BackgroundLow diet quality, diabetes, and chronic inflammation are risk factors of liver cancer and chronic liver disease (CLD), but the extent to which insulinemic and inflammatory diets are independently associated with risk of liver cancer and CLD mortality is unknown. MethodsWe conducted a prospective cohort analysis among 78,356 postmenopausal women in the Women’s Health Initiative Observational Study. Two validated dietary indices, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food-frequency questionnaire. Incident cases of liver cancer and CLD mortality were adjudicated via review of medical records and linkage to National Death Index. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models, adjusted for age, diabetes, body mass index, and other covariates. ResultsDuring a median 22.1 y of follow-up, we documented 176 primary liver cancer cases and 156 CLD mortality cases. EDIH was positively associated with incident liver cancer (HRQuartile 4 vs. Quartile 1 = 1.68; 95% CI: 1.00, 2.83; P-trend = 0.05) and CLD mortality (HRQ4 vs. Q1 = 2.28; 95% CI: 1.25, 4.15; P-trend = 0.02) in the multivariable model. EDIP was also positively associated with liver cancer (HRQ4 vs. Q1 = 1.88; 95% CI: 1.17, 3.03; P-trend = 0.009) and CLD mortality (HRQ4 vs. Q1 = 1.85; 95% CI: 1.09, 3.15; P-trend = 0.007). Estimates remained significant and robust in sensitivity analyses. Further analyses indicated positive associations for refined grains, processed meat, sugary beverages, and eggs, and inverse associations for coffee/tea and poultry. ConclusionsDietary insulinemic and inflammatory potentials were independently associated with higher risk of liver cancer and CLD mortality in U.S. postmenopausal women. These findings suggest a potential role for diet modification to reduce risk of liver cancer and CLD.

Abstract 6456: Association of dietary inflammatory and insulinemic potential with risk of liver cancer and chronic liver disease mortality

Abstract Background: Increasing burdens of liver cancer and chronic liver disease (CLD) urge investigation of modifiable risk factors for primary prevention. Despite strong experimental evidence showing the role of chronic insulin resistance/hyperinsulinemia and inflammation in liver cancer and CLD, whether the insulinemic and inflammatory potential of diet are independently associated with higher risk of these outcomes requires further investigation. Methods: We conducted a prospective cohort study among 78,356 postmenopausal women in the Women’s Health Initiative Observational Study. Two validated dietary indices that predict circulating C-peptide or biomarkers of inflammation, namely, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food frequency questionnaire. Incident cases of liver cancer and CLD mortality were ascertained via review of medical records and linkage to national registries. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazard models, adjusted for age, diabetes, body mass index (BMI), and other covariates. Results: During a median 22.1 years of follow-up, we documented 176 primary liver cancer cases and 156 CLD mortality cases. The EDIH was positively associated with incident liver cancer risk (HRQuartile4 vs. Quartile1 = 1.70; 95% CI: 1.03, 2.81; p-trend = 0.03) and CLD mortality risk (HRQ4 vs. Q1 = 2.75; 95% CI: 1.54, 4.93; p-trend = 0.01) in the multivariable adjusted model, including diabetes and BMI as covariates. The EDIP was also positively associated with liver cancer (HRQ4 vs. Q1 = 1.93; 95% CI: 1.21, 3.09; p-trend &amp;lt;0.001) and CLD mortality risk (HRQ4 vs. Q1 = 2.09; 95% CI: 1.24, 3.52; p-trend &amp;lt;0.001) in the multivariable adjusted model. The estimates remained significant and robust in sensitivity analyses, after exclusion of cases in the first 2 years of follow-up or with liver disease history. There was no additive effect between the two dietary indices. Further analyses of individual food groups and liver outcomes indicated positive associations with refined grains, processed meat, butter, and eggs, and inverse associations with coffee, poultry, green leafy vegetables, and dark yellow vegetables. Conclusions: Dietary insulinemic and inflammatory potential were independently associated with higher risk of liver cancer and CLD mortality in US postmenopausal women. Monitoring dietary patterns to reduce chronic hyperinsulinemia and inflammation may contribute to the primary prevention of liver cancer and CLD mortality. Citation Format: Xinyuan Zhang, Longgang Zhao, Cami Christopher, Fred K. Tabung, Wei Bao, David O. Garcia, Marian L. Neuhouser, Aladdin H. Shadyab, Nazmus Saquib, Lesley Tinker, Xuehong Zhang. Association of dietary inflammatory and insulinemic potential with risk of liver cancer and chronic liver disease mortality. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6456.

N-nitrosodimethylamine-Contaminated Valsartan and Risk of Cancer: A Nationwide Study of 1.4 Million Valsartan Users.

Background Since July 2018, numerous lots of valsartan have been found to be contaminated with N-nitrosodimethylamine (NDMA). We aimed to assess the association between exposure to valsartan products contaminated with NDMA and the risk of cancer. Methods and Results This study was based on data from the Système National des Données de Santé, which is a national database that includes all French residents' health-related expenses. The target population was consumers of valsartan between January 1, 2013 and December 31, 2017, aged between 40 and 80 years old. The association of exposure to contaminated valsartan with the occurrence of any malignancy and cancer by location was evaluated by fitting Cox proportional hazards models weighted by the inverse probability of treatment. A total of 1.4 million subjects without any history of cancer were included. A total of 986 126 and 670 388 patients were exposed to NDMA-contaminated and uncontaminated valsartan, respectively. The use of the NDMA-contaminated valsartan did not increase the overall risk of cancer (adjusted hazard ratio [aHR], 0.99 [95% CI, 0.98-1.0]). However, exposed patients had a higher risk of liver cancer (aHR, 1.12 [95% CI, 1.04-1.22]) and melanoma (aHR, 1.10 [95% CI, 1.03-1.18]). We estimated a mean of 3.7 and 5.8 extra cases per year per 100 000 person-years of liver cancer and melanoma, respectively. Conclusions Our study was the largest to date to examine cancer risks associated with exposure to NDMA-contaminated valsartan. Our findings suggest a slight increased risk of liver cancer and melanoma in patients exposed to NDMA in regularly taken medications.

Daytime napping and risk of liver cancer: A large population-based prospective cohort study

Introduction and ObjectivesLiver cancer is a major cause of morbidity and mortality in Japan and worldwide. Daytime napping is a common behavior, especially among older adults, that was related in previous research to unfavorable health conditions. Herein, we investigated the association between daytime napping and liver cancer risk. Materials and MethodsIn this prospective cohort study, data from 51,185 participants aged 40–79 years and registered in the Japan Collaborative Cohort Study (JACC Study) were analyzed. Incident cases of liver cancer were diagnosed using cancer registries, hospital records, and death certificates. Daytime napping was assessed using the JACC baseline self-administered questionnaire. We used the Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident liver cancer among participants in the age categories of the 40s, 50s, 60s, and 70s who reported daytime napping compared with their counterparts who did not. ResultsWithin 669,734 person-years of follow-up, 341 participants developed liver cancer. Daytime napping was associated with a higher risk of liver cancer among participants who were in their 60s and 70s of age after adjusting for sex: HRs (95% CIs) 1.88 (1.35–2.61) and 1.96 (1.18–3.26), lifestyle and medical history: 1.76 (1.27–2.47) and 1.82 (1.07–3.09), and history of liver diseases: 1.66 (1.18–2.34) and 1.72 (1.01–2.94), respectively. No associations were detected among participants from the 40s and 50s age groups. ConclusionsDaytime napping was associated with a higher risk of liver cancer among older adults.

Cancer Risk following Residential Exposure to Airborne Polychlorinated Biphenyls: A Danish Register-Based Cohort Study.

Background:Polychlorinated biphenyls (PCBs) are biopersistent chemicals classified as human carcinogens. This classification is primarily based on evidence on higher-chlorinated PCBs found in food. The carcinogenic potential of airborne lower-chlorinated PCBs remains largely unexplored.Objectives:We aimed to investigate cancer risk following residential exposure to airborne PCBs.Methods:Cancer risk was examined in the Health Effects of PCBs in Indoor Air (HESPAIR) cohort of 38,613 residents of two partly PCB-contaminated residential areas in Greater Copenhagen, identified by nationwide registries. PCB exposure was based on relocation dates and indoor air PCB measurements in subsets of apartments. Cancer diagnoses were extracted from the Danish Cancer Registry for the follow-up period of 1970–2018. We estimated adjusted hazard ratios with time-varying cumulative exposure and a 10-y lag using Cox regression.Results:Overall risk of cancer was not associated with , [hazard ratio (HR) for high-exposed vs. low-exposed ; 95% confidence interval (CI): 0.88, 1.09], but residents exposed to had higher risk of liver cancer (HR ; 95% CI: 1.28, 6.15) and meningiomas (HR ; 95% CI: 1.84, 6.64), with indications of exposure–response relationships. Results were suggestive of a higher risk of pancreatic cancer (HR ; 95% CI: 0.95, 2.64) at the highest aggregated PCB level. For testis cancer, a higher risk was observed among residents exposed to relative to residents exposed to (HR ; 95% CI: 1.41, 6.28), but the risk was not higher for residents exposed to . Apart from this, the risk of specific cancers was similar across exposure groups.Discussion:In this, to our knowledge, first population-based cohort study of residential exposure to airborne PCBs, we found no association between exposure to PCBs in indoor air in private homes and the risk for most of the specific cancers. Higher risk of liver cancer and meningiomas were observed. https://doi.org/10.1289/EHP10605

Effect evaluation of the primary screening strategy for liver cancer in rural areas of China

Objective: To estimate the effectiveness of the primary screening strategy for liver cancer in rural areas to provide basic information for the optimization and perfection of the technical program for the early detection and treatment of liver cancer. Methods: Residents including males aged 35-64 and females aged 45-64 from 9 counties in rural China between 2013 and 2015 were selected as the target population. The participant was classified into a high-risk and non-high-risk group based on the standardized questionnaire or HBsAg, and the Chi-squared test was applied to compare differences between the two groups. The Cox proportional hazard regression models were applied to assess hazard ratio (HR) and its 95% confidence interval (CI). Results: 358 348 participants were recruited from 2013 to 2015. 1 196 individuals were identified with liver cancer until December 31, 2021, with an incidence density of 52.0/10(5) person-years. Of the participants, 54 650 were assessed as high risk (15.3%) based on the questionnaire and the status of HBsAg. The high-risk population had a higher incidence density (168.3/10(5) person-years vs 31.5/10(5) person-years) and higher risk of developing liver cancer (HR=2.98, 95% CI=2.64-3.35), compared to the non-high-risk group. Based on the questionnaire-based high-risk assessment system, 47 884 (13.4%) individuals were identified as high risk, who showed statistical differences in terms of incidence density and incidence risk, in comparison to the low-risk population (all P<0.05). HBsAg can screen out a higher proportion of high-risk individuals who are women, non-smokers, non-drinkers, and individuals without a family history of liver cancer (all P<0.05). The sensitivity analysis of the effectiveness of the whole primary screening method is stable, and high-risk individuals still had a higher risk of liver cancer. Conclusions: The primary screening method of the questionnaire-based risk assessment system and HBsAg can achieve satisfactory effectiveness. The questionnaire-based risk assessment system could identify high-risk individuals to some extent, however, it still needs to be improved to meet the actual requirements.

Prevalence of Primary Liver Cancer is Affected by Place of Birth in Hispanic People Residing in the United States: All of Us Research Program Report.

Hispanic individuals have a disproportionately higher incidence and mortality for stomach, cervix, and liver cancers compared to Non-Hispanic White people. Since disparities in cancer incidence are influenced by multiple factors including immigration, elucidating the effect of birthplace and exposure to risk factors on the prevalence of these cancers is crucial for identifying high-risk populations and target risk reduction interventions. The National Institutes of Health All of Us Research Program is a prospective, multidimensional biomedical data resource of underrepresented, minoritized people. The Registered Tier Dataset v5 was utilized to evaluate the prevalence and risk of stomach, cervix, and liver cancers among United States (US) born and non-US born Hispanic participants. Of over 434000 current participants, 60540 are Hispanic; 30803 (50.9%) reported being US born and 29294 (48.4%) non-US born. Non-US born Hispanic participants had significantly higher prevalence (.39% vs .21%, P < .001) and associated risk (OR 1.84, 95% CI 1.29-2.64, P < .001) of liver cancer, and trend towards higher prevalence of stomach (.14% vs .09%, P = .076) and cervix cancers (.27% vs .20%, P = .083) compared to US born counterparts. US born Hispanic patients with these 3 cancers were significantly younger than non-US born cohort (mean age 56.8 vs 61.7years, P < .001). This is the first report using All of Us data to show that non-US born Hispanic participants have a higher risk of liver cancer compared to US born participants. Further analyses, including genomic studies, are necessary to understand these differences and identify targets for risk reduction interventions.

Prospective associations of hemoglobin A1c and c-peptide with risk of diabetes-related cancers in the Cancer Prevention Study-II Nutrition Cohort.

Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A1c (HbA1c) and c-peptide with cancers associated with self-reported T2DM. This study was drawn from a prospective cohort of 32,383 women and men who provided blood specimens at baseline: c-peptide and HbA1c were assessed in 3,000 randomly selected participants who were cancer-free-at-baseline and an additional 2,281 participants who were cancer-free-at-baseline and subsequently diagnosed with incident colorectal, liver, pancreatic, female breast, endometrial, ovarian, bladder, or kidney cancers. Weighted-Cox regression models estimated hazards ratios (HRs) and 95% confidence intervals (CI), adjusted for covariates. C-peptide was associated with higher risk of liver cancer (per standard deviation (SD) HR: 1.80; 95%CI: 1.32-2.46). HbA1c was associated with higher risk of pancreatic cancer (per SD HR: 1.21 95%CI 1.05-1.40) and with some suggestion of higher risks for all-cancers-of-interest (per SD HR: 1.05; 95%CI: 0.99-1.11) and colorectal (per SD HR: 1.09; 95%CI: 0.98-1.20), ovarian (per SD HR: 1.18; 95%CI 0.96-1.45) and bladder (per SD HR: 1.08; 95%CI 0.96-1.21) cancers. Compared to no self-reported T2DM and HbA1c <6.5% (reference group), self-reported T2DM and HbA1c <6.5% (i.e., T2DM in good glycemic control) was not associated with risk of colorectal cancer, whereas it was associated with higher risks of all-cancers-of-interest combined (HR: 1.28; 95%CI: 1.01-1.62), especially for breast and endometrial cancers. Additional large, prospective studies are needed to further explore the roles of hyperglycemia, hyperinsulinemia, and related metabolic traits with T2DM-associated cancers to better understand the mechanisms underlying the self-reported T2DM-cancer association and to identify persons at higher cancer risk.

Metabolic syndrome and its component traits present gender-specific association with liver cancer risk: a prospective cohort study

Background & AimsLittle is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort.MethodsWe included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method.ResultsOver a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27–1.72] and central obesity [HR 1.65, 95% CI 1.18–2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk.ConclusionsMetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.