Increased Risk Of Liver Cancer Research Articles

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.53-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. [Correction added on 19 August 2024, after first online publication: In the preceding sentence, the value '3.534' has been changed to '3.54'.]. No associations were observed for the other medications. Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

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.

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.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Factor modification in the association between high-density lipoprotein cholesterol and liver cancer risk in a nationwide cohort.

The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported. This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65-2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10-1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50-59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70-2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84-2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29-6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10-1.93). This association was similarly observed in Model III. Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women.

Effects of Genetic Polymorphisms of LINC-PINT Gene on Liver Cancer Susceptibility in the Chinese Han Population

Objective: Liver cancer (LC) is the most common cause of cancer mortality. This study aimed to explore the impact of LINC-PINT polymorphisms on LC. Materials &amp; methods: The authors recruited 591 LC patients and 592 healthy controls. The association between LINC-PINT polymorphisms and susceptibility to LC was determined by logistic regression analysis. Results: The authors found that rs157916 and rs16873842 reduced susceptibility to LC. rs157916 decreased LC risk in patients aged &lt;55 years, nondrinkers and those with BMI &lt;24. rs16873842 had a protective role against LC in patients aged ≥55 years, women, nonsmokers and those with BMI ≥24. rs7801029 decreased LC risk in patients with BMI &lt;24. rs28662387 increased LC risk in women. Conclusion: LINC-PINT polymorphisms exert a protective effect against LC.

Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project

Background & AimsIncidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. MethodsConcentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography–mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. ResultsHigher concentrations of total testosterone (OR per one-unit increase in log2 = 1.77, 95% CI = 1.38–2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21–2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22–20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27–2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33–0.68). ConclusionsHigher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. Impact and implicationsThis study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.

Diets Rich in Refined Fiber May Increase Liver Cancer Risk

Diets Rich in Refined Fiber May Increase Liver Cancer Risk

A prospective cohort study of cigarette smoking, alcohol drinking and liver cancer incidence in Chinese men

Population-based prospective studies on the associations of cigarette smoking, alcohol drinking, and primary liver cancer remain limited in Mainland China. Our study was designed to evaluate such relationships in middle-aged Chinese men. Self-reported habits of cigarette smoking and alcohol drinking were obtained from all cohort members at the baseline survey. The outcomes were identified through in-person follow-up and annual record linkage to multiple statistics of vital and cancer registration. Age-adjusted and multivariable-adjusted hazard ratio (HR) and their corresponding 95% confidence interval (CI) were estimated utilizing the Cox regression model. After a median follow-up of 12.31 years, 329 cases of incident primary liver cancer occurred among 45 266 male participants. Compared with never smoker, former smoker was positively associated with liver cancer risk, with a multivariable-adjusted HR of 1.42 (95% CI 1.02-1.98). Individuals who had smoked for more than 40 years had a 49% increased risk of liver cancer (HR≥40 years 1.49, 95% CI 1.04-2.14). The association of alcohol drinking with liver cancer showed no statistical significance. Our study provided evidence that cigarette smoking was positively associated with an increased liver cancer risk among Chinese men. Attention to such non-viral modifiable risk factors to prevent liver cancer effectively is needed.

Association of Plasma Iron Status with Subsequent Risk of Total and Site-Specific Cancer: A Large Case-Cohort Study within JPHC Study.

High ferritin and low hepcidin levels in the plasma were associated with increased liver cancer risk. Evaluating iron metabolism including hepcidin levels may help identify people with high liver cancer risk.

Aflatoxin M1 in milk does not contribute substantially to global liver cancer incidence

For 60 y, it has been known that aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus fungi in certain food and feed crops, causes hepatocellular carcinoma (liver cancer; HCC) in humans. The annual global burden of AFB1-related HCC has been estimated. However, much less is known about the potential carcinogenic impact of a metabolite of AFB1 called aflatoxin M1 (AFM1), which is secreted in milk when dairy animals consume AFB1-contaminated feed. The cancer risk of AFM1 to humans from milk consumption has not yet been evaluated. We sought to estimate the global risk of AFM1-related liver cancer through liquid milk consumption, accounting for possible synergies between AFM1 and chronic infection with hepatitis B virus (HBV) in increasing cancer risk. We conducted a quantitative cancer risk assessment by analyzing extensive datasets of national population sizes, dairy consumption patterns, AFM1 concentrations in milk in 40 nations, and chronic HBV prevalence. Two separate cancer risk assessments were conducted: assuming a possible synergy between AFM1 and HBV in increasing cancer risk in a manner similar to that of AFB1 and HBV, and assuming no such synergy. If there is no synergy between AFM1 and HBV, AFM1 may contribute ∼0.001% of total annual HCC cases globally. If there is synergy between AFM1 and HBV infection, AFM1 may contribute ∼0.003% of all HCC cases worldwide. In each case, the total expected AFM1-attributable cancer cases are ∼13-32 worldwide. AFM1 exposure through liquid milk consumption does not substantially increase liver cancer risk in humans. Policymakers should consider this low risk against the nutritional benefits of milk consumption, particularly to children, in a current global situation of milk being discarded because of AFM1 concentrations exceeding regulatory standards.

Association between working hours and cancer risk in Japan: The Japan public health center-based prospective study

In this study, we evaluated the association between working hours and cancer risk in the Japanese population, which has not been evaluated. Using a cohort database from a Japan Public Health Center-based Prospective Study, we evaluated 26 738 participants (16 351 men and 10387 women), who responded to a questionnaire about working hours and followed these participants from 1993-1994 to 2013. Participants were divided into four groups according to working hours (≤6, 7-8, 9-10, ≥11 h/day). The hazard ratio (HR) and 95% confidence interval (CI) of each cancer incidence were calculated using a multivariable-adjusted Cox proportional hazard model. During 488 383 person-years of follow-up, 481 patients with newly diagnosed cancers were identified. There was no clear association between long working hours and overall cancer, lung cancer, and stomach cancer risks. Long working hours tended to increase prostate cancer risk in men and breast cancer risk in women, although the difference was not statistically significant. Increased liver cancer risk with short working hours (HR [95% CI]; 3.15 [1.44-6.88] in the ≤6h/day group vs. 7-8 h/day) was observed. Colorectal cancer also tended to increase risk in short working hours, however, there were not statistically significance. In this population, long working hours were not associated with cancer risk with statistically significance. The association between short working hours and liver cancer risk was observed, probably due to the reverse causation of liver cancer.

Abstract IA-43: Designing individual-level and structural interventions to reduce and eliminate racial disparities in liver cancer

Abstract Over the past two decades, the incidence of hepatocellular carcinoma (HCC) has increased dramatically, in the United States and worldwide. The tremendous racial diversity in the United States allows for evaluation of racial differences in HCC risk and outcomes. Blacks, Asians and Hispanics all have increased liver cancer risk compared to non-Hispanic Whites. The cause of this disparity is poorly understood but is thought to be multi-factorial. The prevalence and etiology of chronic liver disease differs amongst racial subgroups; nonalcoholic fatty liver disease is most prevalent in Hispanics, while Blacks and Asians are disproportionately affected by viral hepatitis. Moreover, there are substantial racial inequalities with regards to access to comprehensive health care. In addition to racial differences in HCC risk, there are significant racial disparities in cancer stage at HCC diagnosis and receipt of appropriate cancer treatment. Multiple retrospective studies have confirmed significant disparities in survival after HCC diagnosis; Blacks in the United States and worldwide have the lowest survival, compared to other races. There are many stages along the cancer continuum where clinicians and researchers can intervene to improve how individuals living with liver disease are diagnosed, which could subsequently reduce the risk of HCC and improve outcomes. Using hepatitis B as a case study, this lecture will discuss individual-level interventions as well as the necessary structural interventions targeting healthcare policy, organizations, institutions and vulnerable communities that will be required to achieve widespread reduction in HCC-related disparities. Citation Format: Patricia D. Jones. Designing individual-level and structural interventions to reduce and eliminate racial disparities in liver cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA-43.

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.

Dose-Response Association between Adiposity and Liver Cancer Incidence: A Prospective Cohort Study among Non-Smoking and Non-Alcohol-Drinking Chinese Women.

Based on a population with very low prevalence of smoking and alcohol drinking, we examined the associations between overall obesity and fat distribution in middle age, obesity in early adulthood, and adult weight gain with the risk of liver cancer incidence. The associations between body mass index (BMI) at study enrollment and at age 20, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), adult weight gain, and annual average weight gain with the risk of liver cancer were estimated using Cox regression models. Multivariable-adjusted HRs and 95% confidence intervals (CIs) were calculated. After a mean follow-up time of 17.5 years, 241 liver cancer cases were identified from 69,296 participants. The HRs for per 5-kg/m2 increment of BMI, per 10-cm increment of WC and HC, and per 0.1-unit increment of WHtR in middle age were 1.29 (95% CI, 1.07-1.57), 1.23 (95% CI, 1.05-1.43), 1.30 (95% CI, 1.10-1.55), and 1.37 (95% CI, 1.07-1.75), respectively. The HRs for per 5-kg increment of absolute adult weight gain and per 0.5-kg/year increment of annual average weight gain were 1.15 (95% CI, 1.06-1.25) and 1.44 (95% CI, 1.08-1.92). Overall and abdominal obesity in middle age and weight gain through adulthood were positively associated with liver cancer risk among non-smoking and non-alcohol-drinking women. Based on a cohort of non-smoking and non-alcohol-drinking women, the current study confirmed the association between obesity in middle age and increased liver cancer risk and suggested weight gain through adulthood as a risk factor for liver cancer.

Dietary fat intake and liver cancer risk: A prospective cohort study in Chinese women.

Objective:This study aimed to determine whether dietary fat intake increased liver cancer risk in Chinese women from a prospective population-based cohort.Methods:A total of 72,704 Chinese women were followed up from the time of baseline recruitment (1996–2000) to the end of 2016. Dietary fat intake was calculated using a validated food frequency questionnaire. The Cox regression model was used to assess the hazard ratio (HR) and 95% confidence intervals (CI) for dietary fat intake and liver cancer risk.Results:We identified 252 incident liver cancer cases out of 1,267,845 person-years during the overall follow-up time. Null associations, neither in quartiles nor per standard deviation (SD) increment, were detected between liver cancer risk and dietary total fat, fat subtypes and subtype ratios, and food sources. The HR (95% CI) of the 1-SD increment was 1.03 (0.90–1.17) for total fat, 1.06 (0.93–1.20) for saturated fat, 1.06 (0.93–1.21) for monounsaturated fat, and 1.00 (0.89–1.13) for polyunsaturated fat. Similar null associations were observed in stratification analyses according to body mass index and menopausal status.Conclusions:In our prospective cohort study, no significant association was observed in Chinese women between dietary fat and liver cancer risk, and in stratification and sensitivity analyses.

Chemical Risk Factors of Primary Liver Cancer: An Update.

Primary liver cancer has the sixth highest incidence and fourth highest cancer mortality worldwide. Hepatitis B is the leading cause of liver cancer, though its incidence is decreasing with vaccination. Alcohol is the leading cause of liver transplant, cirrhosis, and cancer in the developed world, and is projected to surpass hepatitis B as the leading hepatic cancer etiology worldwide. Tobacco smoking has shown a positive association with liver cancer in a majority of studies, though not all. Aflatoxin, a mycotoxin produced by Aspergillus, is estimated to account for 3–20% of global liver cancer cases, 40% of which occur in sub-Saharan Africa. These statistics are confounded by the prevalence of hepatitis B, which may have a synergistic effect on hepatic carcinogenesis. Aflatoxin is ingested and likely inhaled from agricultural products, placing farmers, food processors, and textile workers in developing nations at risk. Vinyl-chloride is used in the production of PVC plastics and causes rare liver angiosarcoma, hepatocellular carcinoma, and other neoplasms. Arsenic and cadmium are naturally-occurring, hepatocarcinogenic metals with high occupational exposure in industries involving coal, metals, plastics, and batteries. Millions of laborers in waste-disposal and manufacturing are exposed to organic solvents and N-nitrosamines, which vary from carcinogenic (group 1) to possibly carcinogenic (group 2B) in their IARC designation. Insecticide DDT is possibly hepatocarcinogenic (group 2B), though continues to be used for malaria control in the developing world. While suggested by case reports, anabolic steroids and oral contraceptives have not been shown to increase liver cancer risk in large studies.

Ingestion of nitrate and nitrite from drinking water and diet and cancers of the gastrointestinal tract in Iowa women

Background: Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potent animal carcinogens in the gastrointestinal tract. Methods: We evaluated nitrate ingestion from public drinking water supplies (PWS), private well use, and dietary nitrate and nitrite intakes in relation to incidence (through 2014) of cancers of the esophagus (n=37), stomach (97), small intestine (47), liver (56), and gallbladder (66) in the Iowa Women’s Health Study (42,000 women ages 50-75 in 1986). Historical nitrate measurements from PWS were linked to the enrollment address by duration. We computed average concentrations and number of years &gt;5 mg/L NO3-N (½ the maximum contaminant level [MCL]). Dietary nitrate and nitrite were estimated using a food frequency questionnaire. We used Cox proportional hazards models to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: In adjusted models, liver cancer risk was elevated among private well users (HR=2.5, CI 0.8-8.5) and those with any years &gt;5 mg/L NO3-N (HR=2.0, CI 0.8-4.9); there was no association with average concentrations (HRper1mg/L NO3-N =1.1, CI 0.7-1.7). Private well use and PWS nitrate concentrations were not associated with other cancers. Dietary nitrate and nitrite from plants was inversely associated with small intestine (HRQ4vsQ1=0.4, CI 0.1-0.9) and gall bladder cancer (HRQ4vsQ1=0.3, CI 0.1-0.8), respectively; there were no associations for the other cancers. Nitrite intake from processed meats was associated with increased risk of stomach (HRnitriteQ4vsQ1=1.7, CI 1.0-3.0) and elevated risk of liver cancer (HRnitriteQ4vsQ1=1.8, CI 0.8-4.0) but was inversely associated with small intestine cancer (HRnitriteQ4vsQ1=0.4, CI 0.1-1.0). Power was limited, but there was no evidence for effect modification by vitamin C and red meat, factors affecting nitrosation. Conclusion: We found novel suggestive evidence that private well use and PWS nitrate may increase liver cancer risk. These associations should be evaluated in studies with larger case numbers.

Cancer risk in patients with primary immune thrombocytopenia – A Swedish nationwide register study

BackgroundImmune thrombocytopenia (ITP) is an autoimmune disease treated with immunosuppressive agents, thrombopoietin receptor agonists, immunomodulation drugs and/or splenectomy. Patients with ITP have been found to have increased risk ofhematological malignancies. Studies investigating stomach/liver cancer are contradictory and the risk of developing other solid tumors is largely unknown. We aimed at estimating risk of overall and organ-specific cancers in patients with primary ITP. MethodsThe study population was Swedish patients with at least one ITP diagnosis recorded in the National Patient Register and a 1:10 matched comparison cohort from the population. The study period covers 1997−2016. The Cancer Register and the Cause of Death Register provided data on malignancies and deaths, respectively. Primary ITP was identified using an established algorithm. We used time-split Cox models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs), adjusted for age, sex, index-year, county, income, education, Charlson score and number of in- and outpatient contacts. ResultsIn total 66,134 individuals were included in the study. Patients with ITP had higher risk of gastro-intestinal, skin (all morphologies), lymphoid and hematological cancers. Adjusted HR (95 % CI) for cancer was 1.37 (1.27–1.48), with highest risk during the first year, but with increased risk remaining for up to 20 years for men. For women, the overall risk was increased during the first year, HR (95 % CI) 2.00 (1.55–2.60). A significantly increased liver cancer risk was seen up to 9 years after diagnosis. ConclusionPatients with primary ITP have higher risk of cancer than the population. The observed increased risk does not seem to be solely due to surveillance bias, but might be associated with ITP or its treatments. Treating hematologists need to have high index of suspicion for cancer.

Association between periodontal disease, tooth loss and liver diseases risk.

The purpose of this study is to assess the associations between periodontal disease, tooth loss and liver diseases. PubMed and Embase databases were utilized to search eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to assess the associations between periodontal disease, tooth loss and liver diseases risk. Our results indicated positive associations between periodontal disease and non-alcoholic fatty liver disease (NAFLD) (OR=1.19, 95% CI=1.06-1.33), liver cirrhosis (OR=2.28, 95% CI=1.50-3.48) and elevated transaminase level risk (OR=1.08, 95% CI=1.02-1.15). Moreover, tooth loss could increase NAFLD (OR=1.33, 95% CI=1.12- 1.56) and liver cancer risk (OR=1.34, 95% CI=1.04-1.74), and every five increment in tooth loss was associated with 5% increased liver cancer risk (OR=1.05, 95% CI=1.01 - 1.10) with a linear relationship. In addition, tooth loss had a positive tendency towards liver cirrhosis risk (OR=2.03, 95% CI=0.85-4.85) although there was no statistical significance. Periodontal disease and tooth loss are positively associated with liver diseases including NAFLD, elevated transaminase level, liver cirrhosis and liver cancer.