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Background Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia. Methods We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex. Results N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; P trend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (P interaction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (P interaction = .02). We found no consistent patterns of association with other PFAS or differences by sex. Conclusions These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid. [ABSTRACT FROM AUTHOR]

Human exposure to per‐ and polyfluoroalkyl substances (PFAS) occurs globally through contaminated food, dust, and drinking water. Studies of PFAS and thyroid cancer have been limited. We conducted a nested case‐control study of prediagnostic serum levels of 19 PFAS and papillary thyroid cancer (400 cases, 400 controls) in the Finnish Maternity Cohort (pregnancies 1986‐2010; follow‐up through 2016), individually matched on sample year and age. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for log2 transformed and categorical exposures, overall and stratified by calendar period, birth cohort, and median age at diagnosis. We adjusted for other PFAS with Spearman correlation rho = 0.3‐0.6. Seven PFAS, including perfluoroctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), N‐ethyl‐perfluorooctane sulfonamidoacetic acid (EtFOSAA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonic acid (PFHxS) were detected in >50% of women. These PFAS were not associated with risk of thyroid cancer, except for PFHxS, which was inversely associated (OR log2 = 0.82, 95% CI: 0.70‐0.97). We observed suggestive but imprecise increased risks associated with PFOA, PFOS, and EtFOSAA for those diagnosed at ages <40 years, whereas associations were null or inverse among those diagnosed at 40+ years (P‐interaction:.02,.08,.13, respectively). There was little evidence of other interactions. These results show no clear association between PFAS and papillary thyroid cancer risk. Future work would benefit from evaluation of these relationships among those with higher exposure levels and during periods of early development when the thyroid gland may be more susceptible to environmental harms. [ABSTRACT FROM AUTHOR]

In pre‐disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high‐resolution mass spectrometry based untargeted lipidomics analysis of pre‐diagnostic serum samples from a nested case‐control study (219 liver cancer cases and 219 controls) within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) <0.05. A chemical set enrichment analysis (ChemRICH) and co‐regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs) and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl‐CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre‐diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro‐cell growth and anti‐apoptotic tissue environment and, in turn, support liver cancer initiation. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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. Results: 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. Conclusions: Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers. [ABSTRACT FROM AUTHOR]

Background: Military and general populations differ in factors related to cancer occurrence and diagnosis. This study compared incidence of colorectal, lung, prostate, testicular, breast, and cervical cancers between the US military and general US populations. Methods: Data from the US Department of Defense's Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were analyzed. Persons in ACTUR were active‐duty members 20–59 years old during 1990–013. The same criteria applied to persons in SEER. Age‐adjusted incidence rates, incidence rate ratios, and 95% confidence intervals were calculated by sex, race, age, and cancer stage. Temporal trends were analyzed. Results: ACTUR had higher rates of prostate and breast cancers, particularly in 40‐ to 59‐year‐olds. Further analyses by tumor stage showed this was primarily confined to localized stage. Incidence rates of colorectal, lung, testicular, and cervical cancers were significantly lower in ACTUR than in SEER, primarily for regional and distant tumors in men. Temporal incidence trends were generally similar overall and by stage between the populations, although distant colorectal cancer incidence tended to decrease starting in 2006 in ACTUR whereas it increased during the same period in SEER. Conclusion: Higher rates of breast and prostate cancers in servicemembers 40–59 years of age than in the general population may result from greater cancer screening utilization or cumulative military exposures. Lower incidence of other cancers in servicemembers may be associated with better health status. Incidence rates of local staged prostate and breast cancers were higher in the military than the general population among 40‐ to 59‐year‐olds. Incidence rates of colorectal, lung, and testicular cancers among men were lower in the military than the general population, particularly among 20‐ to 39‐year‐olds. [ABSTRACT FROM AUTHOR]

Background: In the last decades, an increasing incidence of testicular cancer has been observed in several countries worldwide. Although mortality rates have been variable in many countries, little information is available from Latin America and the Caribbean (LAC). Therefore, we examined mortality trends of testicular cancer in the last two decades. Methods: Age-standardized mortality rates (ASMR) of testicular cancer per 100,000 men-years were estimated using the World Health Organization mortality database from 1997 to 2019. We examined the mortality trends and computed annual percent change (APC) for all ages and the following age groups, 15–29, 30–44, 15–44, and ≥ 45 years. Results: Ten countries had mortality rates greater than 0.43 per 100,000 men, with the highest rates for Chile, Mexico, and Argentina. Significant increases in mortality rates were observed in Argentina, Brazil Colombia, and Mexico in all ages, and < 45 years, while Colombia, Ecuador, Mexico, and Peru reported significant downward trends in males aged ≥ 45 years. Only Chile showed significant decreases for all ages and age groups studied. Conclusion: Mortality by testicular cancer increased among LAC countries in males of all ages and across age groups. A reduction in mortality rates was observed only in Chilean males of all ages and in men ≥ 45 years in several countries. Strengthening of early detection among symptomatic males may decrease the mortality by this neoplasm. [ABSTRACT FROM AUTHOR]

The Military Health System (MHS) of the US Department of Defense (DoD) provides comprehensive medical care to over nine million beneficiaries, including active-duty members, reservists, activated National Guard, military retirees, and their family members. The MHS generates an extensive database containing administrative claims and medical encounter data, while the DoD also maintains a cancer registry that collects information about the occurrence of cancer among its beneficiaries who receive care at military treatment facilities. Collating data from the two sources diminishes the limitations of using registry or medical claims data alone for cancer research and extends their usage. To facilitate cancer research using the unique military health resources, a computer interface linking the two databases has been developed, called Military Cancer Epidemiology , or MilCanEpi. The intent of this article is to provide an overview of the MilCanEpi data system, describing its components, structure, potential uses, and limitations. Military Cancer Epidemiology database offers unique resource to study cancer in the Department of Defense. [ABSTRACT FROM AUTHOR]

Key Points: Question: Is greater intake of sugar-sweetened beverages associated with greater risk of liver cancer or chronic liver disease mortality? Findings: In 98 786 postmenopausal women followed up for a median of 20.9 years, compared with consuming 3 servings or less of sugar-sweetened beverages per month, women consuming 1 or more servings per day had significantly higher rates of liver cancer (18.0 vs 10.3 per 100 000 person-years; adjusted hazard ratio [HR], 1.85) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years; adjusted HR, 1.68). Meaning: Compared with 3 or fewer sugar-sweetened beverages per month, consuming 1 or more sugar-sweetened beverages per day was associated with a significantly higher incidence of liver cancer and death from chronic liver diseases. Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: 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. Exposures: 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. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. This observational study evaluated incidence of liver cancer and death from chronic liver disease among postmenopausal women by comparing intake of 3 or fewer servings of sugar-sweetened beverages per month vs intake of 1 or more sugar-sweetened beverages per day. [ABSTRACT FROM AUTHOR]

Gut barrier dysfunction can result in the liver being exposed to an elevated level of gut‐derived bacterial products via portal circulation. Growing evidence suggests that systemic exposure to these bacterial products promotes liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, prospective studies have not examined the association between biomarkers of gut barrier dysfunction and HCC risk in a population of hepatitis B or C viral (HBV/HCV) carriers. We investigated whether prediagnostic, circulating biomarkers of gut barrier dysfunction were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)‐HBV and REVEAL‐HCV cohorts from Taiwan. REVEAL‐HBV included 185 cases and 161 matched controls, and REVEAL‐HCV 96 cases and 96 matched controls. The biomarkers quantitated were immunoglobulin A (IgA), IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and LPS‐binding protein (LBP). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarker levels and HCC were calculated using multivariable‐adjusted logistic regression. A doubling of the circulating levels of antiflagellin IgA or LBP was associated with a 76% to 93% increased risk of HBV‐related HCC (OR per one unit change in log2 antiflagellin IgA = 1.76, 95% CI: 1.06‐2.93; OR for LBP = 1.93, 95% CI: 1.10‐3.38). None of the other markers were associated with an increased risk of HBV‐related or HCV‐related HCC. Results were similar when cases diagnosed in the first 5 years of follow‐up were excluded. Our findings contribute to understanding the interplay of gut barrier dysfunction and primary liver cancer etiology. [ABSTRACT FROM AUTHOR]

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a component of firefighting foams used at military installations. Although high PFAS exposures have been related to cancer risks among civilian populations, the effects for military personnel are unclear. OBJECTIVES: We investigated associations between serum PFAS concentrations and testicular germ cell tumors (TGCT) among U.S. Air Force servicemen. METHODS: This nested case–control study involved active-duty Air Force servicemen with sera from the Department of Defense Serum Repository. We selected 530 cases and 530 controls individually matched on birth date, race and ethnicity, year entered the service, and year of sample collection, with prediagnostic serum samples collected between 1988 and 2017. A second prediagnostic sample, collected a median of 4 y after the first, was selected for 187 case–control pairs. Seven PFAS were quantified using isotope-dilution tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression adjusting for military grade, number of deployments, and, in some models, other PFAS, estimated associations between PFAS concentrations (categorized using quartiles among controls) and TGCT. RESULTS: Elevated concentrations of some PFAS were observed for military employment in firefighting [perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid] and service at a base with high PFAS concentrations in drinking water (PFHxS). Elevated PFOS concentrations in the second sample were positively associated with TGCT [OR for fourth vs. first quartile (ORQ4)=2.6, 95% CI: 1.1, 6.4; 푝trend =0.02], including after adjustment for other PFAS (ORQ4 =4.6, 95% CI: 1.4, 15.1; 푝trend =0.009). Associations with PFOS in the first/only samples were weak and not statistically significant. Elevated concentrations of perfluorononanoic acid were inversely associated with TGCT, whereas results were null for other PFAS. DISCUSSION: We identified service-related predictors of PFAS concentrations and increased TGCT relative risks with elevated PFOS concentrations among Air Force servicemen. These findings warrant further investigation in other populations and military service branches. [ABSTRACT FROM AUTHOR]

Background & objectives: The comparison of the incidence of gonadal germ cell tumors among males and females can provide insights that cannot be gained by separately studying these tumors. Material and methods: Incidence data on male and female gonadal germ cell tumors were drawn from the cancer registries of North Rhine‐Westphalia, Germany, and the United States Surveillance, Epidemiology and End Results program, for non‐Hispanic White persons only, for the years 2008–2016. We estimated age‐standardized and age‐, and histology‐specific incidence rates. Results: We included 21,840 male and 716 female gonadal germ cell tumors. Incidence rates among males were higher in Germany (95.8 per million, standard error [SE] 1.1) than in the United States (68.0, SE 0.6), while incidence rates among females were lower in Germany (1.9, SE 0.2) than in the United States (2.6, SE 0.1). The characteristic peak of infantile (age 0–4 years) germ cell tumors among males were missing among females. The age peak of ovarian germ cell tumors occurred 15–20 years earlier (Germany: 10–14 years, United States: 15–19 years) than the age peak of testicular germ cell tumors (30–34 years). The three most common testicular germ cell tumors histologies were seminoma, mixed germ cell tumors, and embryonal carcinoma Among females, the three most common ovarian germ cell tumors histologies were teratoma, yolk sac tumor, monodermal teratomas, and somatic‐type tumors arising from dermoid cysts in both countries. Discussion: The characteristic peak of infantile (age 0–4 years) germ cell tumors among males was missing among females. The shapes of the age‐specific incidence curves are similar for males and females in Germany and the United States, though with much lower incidence rates in females, suggesting a common pathogenesis. Conclusion: The lower rates among females may be due to the lower number of initiated tumors in the absence of the Y‐chromosome, and the earlier peak among females may be due to a younger age at puberty. [ABSTRACT FROM AUTHOR]

Simple Summary: To date: no prospective cohort studies have been used to investigate the role of circulating immunologic markers as they relate to the progression of liver disease in those chronically infected with hepatitis C (HCV). Using data/samples from a prospective cohort of chronically HCV-infected individuals, we sampled 68 individuals who developed cirrhosis, 91 controls who did not develop cirrhosis, and 94 individuals who developed hepatocellular carcinoma (HCC). Using baseline plasma, we examined levels of 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. The findings from this study highlight the important role of immunological markers in predicting HCV-related cirrhosis. Background: Chronic hepatitis C virus (HCV) infection can affect immune response and inflammatory pathways, leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: In a prospective cohort of chronically HCV-infected individuals, we sampled 68 individuals who developed cirrhosis, 91 controls who did not develop cirrhosis, and 94 individuals who developed HCC. Unconditional odds ratios (ORs) from polytomous logistic regression models and canonical discriminant analyses (CDAs) were used to compare categorical (C) baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to produce receiver operating characteristic curves to assess predictive ability of markers. Lastly, biological pathways were assessed in association with cirrhotic development compared to controls. Results: After multivariable adjustment, DEFA-1 (OR: C2v.C1 = 7.73; p < 0.0001), ITGAM (OR: C2v.C1 = 4.03; p = 0.0002), SCF (OR: C4v.C1 = 0.19; p-trend = 0.0001), and CCL11 (OR: C4v.C1 = 0.31; p-trend= 0.002) were all associated with development of cirrhosis compared to controls; these markers, together with clinical/demographics variables, improved prediction of cirrhosis from 55.7% (in clinical/demographic-only model) to 74.9% accuracy. A twelve-marker model based on CDA results further increased prediction of cirrhosis to 88.0%. While six biological pathways were found to be associated with cirrhosis, cell adhesion was the only pathway associated with cirrhosis after Bonferroni correction. In contrast to cirrhosis, DEFA-1 and ITGAM levels were inversely associated with HCC risk. Conclusions: Pending validation, these findings highlight the important role of immunological markers in predicting HCV-related cirrhosis even 11 years post-enrollment. [ABSTRACT FROM AUTHOR]

With 74 500 new cases worldwide in 2020, testicular cancer ranks as the 20th leading cancer type, but is the most common cancer in young men of European ancestry. While testicular cancer incidence has been rising in many populations, mortality trends, at least those in high‐income settings, have been in decline since the 1970s following the introduction of platinum‐based chemotherapy. To examine current incidence and mortality patterns, we extracted the new cases of, and deaths from cancers of the testis from the GLOBOCAN 2020 database. In 2020, testicular cancer was the most common cancer in men aged 15 to 44 in 62 countries worldwide. Incidence rates were highest in West‐, North‐ and South‐Europe and Oceania (age‐standardised rate, ASR ≥7/100 000), followed by North America (5.6/100 000 and lowest (<2/100 000) in Asia and Africa. The mortality rates were highest in Central and South America (0.84 and 0.54 per 100 000, respectively), followed by Eastern and Southern Europe, and Western and Southern Africa. The lowest mortality rates were in Northern Europe, Northern Africa and Eastern Asia (0.16, 0.14, 0.9 per 100 000, respectively). At the country level, incidence rates varied over 100‐fold, from 10/100 000 in Norway, Slovenia, Denmark and Germany to ≤0.10/100 000 in Gambia, Guinea, Liberia, Lesotho. Mortality rates were highest in Fiji, Argentina and Mexico. Our results indicate a higher mortality burden in countries undergoing economic transitions and reinforce the need for more equitable access to testicular cancer diagnosis and treatment globally. [ABSTRACT FROM AUTHOR]

Purpose: Accumulating evidence suggests that light at night (LAN) disrupts circadian rhythms and may increase risk of liver cancer. However, there is no population-based study that examined LAN and liver cancer risk. Therefore, we aimed to investigate the association between outdoor LAN and liver cancer risk in a prospective cohort.Methods: Residential outdoor LAN level was measured from satellite imagery in the NIH-AARP Diet and Health Study, a prospective cohort of 451,945 men and women, 50-71 years old. Relative risks (RR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models that adjusted for known risk factors for liver cancer and neighborhood characteristics.Results: During an average 12.2 years of follow-up, 897 liver cancers, 603 of which were hepatocellular carcinomas (HCC), were diagnosed. Residential outdoor LAN was not associated with risk of liver cancer (RRQ5 vs Q1 = 0.96, 95% CI: 0.77-1.20, p trend = 0.771) or HCC (RRQ5 vs Q1 = 0.82, 95% CI: 0.62-1.07, p trend = 0.425).Conclusion: No association between outdoor LAN and risk of liver cancer or HCC may in part be due to limitations in LAN assessment. More studies on the relationship between light intensity, duration, timing, and wavelength and liver cancer are warranted. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in the United States and is strongly linked to obesity in many, but not all, racial/ethnic groups. It is conceivable that the lack of correspondence is related to differential fat distribution. The study objective was to examine which fat distribution measures best predicted NAFLD by sex within racial/ethnic groups. Methods: The analysis included 1,404 participants from the 2017‐2018 National Health and Nutrition Examination Survey (NHANES). Area under the receiver operating characteristic curve (AUC) analyses compared the ability of dual‐energy x‐ray absorptiometry‐measured percentage total fat and abdominal fat with measured BMI, waist circumference, and waist to height ratio to predict ultrasound transient‐elastography‐assessed NAFLD in each sex and racial/ethnic group. Results: AUC analysis found the best predictors of NAFLD among men were waist circumference and total abdominal fat area (AUC: 84.1%) and the best predictor among women was visceral fat (AUC: 85.2). NAFLD prediction by body fat measures, however, was similar between racial/ethnic groups. Conclusions: The best predictors of NAFLD, using body fat distribution measures, vary by sex but not by racial/ethnic group. [ABSTRACT FROM AUTHOR]

Background Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). Methods We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. BMI was self-reported at ages 20 years and 50 years and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 15.9 years among 138 922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI did not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 years had increased risks of liver cancer (HR = 2.03, 95% CI = 1.26 to 3.28) and BTC (HR = 1.99, 95% CI = 1.16 to 3.39). Compared with participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 years to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI = 1.55 to 4.04) and BTC (HR = 1.83, 95% CI = 1.03 to 3.22). Compared with adults with stable weight (±5 kg) between age 20 years and 50 years, weight gain of 20 kg and greater between ages 20 years and 50 years had higher hazard ratios of 2.24 (95% CI = 1.40 to 3.58) for liver cancer and 1.86 (95% CI = 1.12 to 3.09) for BTC. Conclusions Being overweight and/or obese at age 20 years and BMI trajectories that result in being overweight and/or obese may increase risk for both liver cancer and BTC. [ABSTRACT FROM AUTHOR]

Summary: Background: Non‐alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. Aims: To characterise the relationship between bile acid levels and NAFLD at the population level Methods: We conducted a cross‐sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC–MS/MS. Adjusted prevalence odds ratios (PORadj) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. Results: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1 = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1 = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1 = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1 = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1 = 1.81). Conclusions: The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids. [ABSTRACT FROM AUTHOR]

Persons heterozygous for the risk allele have a two-fold higher risk of liver disease, while persons who are homozygous have a greater than threefold risk.3 In Guatemala, we estimate that >30% of NAFLD among adults may be related to rs738409. Definition of liver disease The primary measure of liver disease was an elevated level of ALT or AST, hereafter referred to as elevated ALT/AST. Keywords: genetics; Guatemala; Latinos; NAFLD; PNPLA3 EN genetics Guatemala Latinos NAFLD PNPLA3 1470 1474 5 06/13/22 20220601 NES 220601 INTRODUCTION Spurred by the epidemics of diabetes and obesity, nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver conditions in the world.1 In the Americas, individuals of Latino ancestry experience disproportionate rates of NAFLD and other liver disorders.2 Genetic susceptibility to NAFLD has been identified, with the I149M polymorphism (rs738409) in the patatin-like phospholipase gene I PNPLA3 i found to be most consistently associated. As shown in Table 2, the frequencies of the previously reported risk allele at each loci were: I PNPLA3 i rs738409 G allele = 0.69, I NCAN i rs2228603 T allele = 0.01, I GCKR i rs780094 T allele = 0.39 and I LYPLAL1 i rs12137855 C allele = 0.94. [Extracted from the article]

The assessment of aflatoxin B1 (AFB1) exposure using isotope-dilution liquid chromatography-mass spectrometry (LCMS) of AFB1-lysine adducts in human serum albumin (HSA) has proven to be a highly productive strategy for the biomonitoring of AFB1 exposure. To compare samples across different individuals and settings, the conventional practice has involved the normalization of raw AFB1-lysine adduct concentrations (e.g., pg/mL serum or plasma) to the total circulating HSA concentration (e.g., pg/mg HSA). It is hypothesized that this practice corrects for technical error, between-person variance in HSA synthesis or AFB1 metabolism, and other factors. However, the validity of this hypothesis has been largely unexamined by empirical analysis. The objective of this work was to test the concept that HSA normalization of AFB1-lysine adduct concentrations effectively adjusts for biological and technical variance and improves AFB1 internal dose estimates. Using data from AFB1-lysine and HSA measurements in 763 subjects, in combination with regression and Monte Carlo simulation techniques, we found that HSA accounts for essentially none of the between-person variance in HSA-normalized (R2 = 0.04) or raw AFB1-lysine measurements (R2 = 0.0001), and that HSA normalization of AFB1-lysine levels with empirical HSA values does not reduce measurement error any better than does the use of simulated data (n = 20,000). These findings were robust across diverse populations (Guatemala, China, Chile), AFB1 exposures (105 range), HSA assays (dye-binding and immunoassay), and disease states (healthy, gallstones, and gallbladder cancer). HSA normalization results in arithmetic transformation with the addition of technical error from the measurement of HSA. Combined with the added analysis time, cost, and sample consumption, these results suggest that it may be prudent to abandon the practice of normalizing adducts to HSA concentration when measuring any HSA adducts—not only AFB1-lys adducts—when using LCMS in serum/plasma. [ABSTRACT FROM AUTHOR]

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Copyright of Salud Pública de México is the property of Instituto Nacional de Salud Publica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. Methods: Four‐hundred twenty‐three individuals were included in the study, in which AFB1‐albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1‐albumin adduct levels categorized into quartiles. Results: The study found a significant association between AFB1‐albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71‐8.19; P‐trend.003). No associations were observed between AFB1‐albumin adduct levels and the other conditions. Conclusions: As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms. [ABSTRACT FROM AUTHOR]

Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. After multivariable adjustment, HGF (Q4v1OR: 3.74; p-trend = 0.0001), SLAMF1 (Q4v1OR: 4.07; p-trend = 0.0001), CSF1 (Q4v1OR: 3.00; p-trend = 0.002), uPA (Q4v1OR: 3.36; p-trend = 0.002), IL-8 (Q4v1OR: 2.83; p-trend = 0.004), and OPG (Q4v1OR: 2.44; p-trend = 0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. In this study, we assessed immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis. [ABSTRACT FROM AUTHOR]

The relationship between dietary factors and liver disease remains poorly understood. This study evaluated the associations of whole grain and dietary fiber intake with liver cancer risk and chronic liver disease mortality. The National Institutes of Health–American Association of Retired Persons Diet and Health Study cohort recruited 485, 717 retired U.S. participants in 1995–1996. Follow-up through 2011 identified 940 incident liver cancer cases and 993 deaths from chronic liver disease. Compared with the lowest, the highest quintile of whole grain intake was associated with lower liver cancer risk (Hazard ratio [HR]Q5 vs. Q1 = 0.78, 95% confidence interval [CI]: 0.63–0.96) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.44, 95% CI: 0.35–0.55) in multivariable Cox models. Dietary fiber was also associated with lower liver cancer risk (HRQ5 vs. Q1 = 0.69, 95% CI: 0.53–0.90) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.37, 95% CI: 0.29–0.48). Fiber from vegetables, beans and grains showed potential protective effect. Here, we show that higher intake of whole grain and dietary fiber are associated with lower risk of liver cancer and liver disease mortality. Higher intake of dietary fiber and whole grains are associated with reduced risk of various diseases including some cancers. Here, the authors estimate reductions in liver cancer of 22% and 31% and chronic liver disease mortality of 56% and 63% associated with increased whole grain and dietary fiber intake, respectively. [ABSTRACT FROM AUTHOR]

Summary: Background: Clinical and experimental studies suggest immunologic proteins contribute to hepatocellular carcinoma (HCC) development. Aim: To evaluate circulating immunologic markers and HCC risk. Methods: From a Taiwanese cohort of chronically hepatitis B virus (HBV)‐infected individuals followed over time (REVEAL‐HBV), we sampled 175 who developed HCC, 117 cirrhosis only, and 165 non‐cirrhotic controls. From a similar Taiwanese cohort of chronically hepatitis C virus (HCV)‐infected individuals (REVEAL‐HCV), we included 94 individuals who developed HCC, 68 cirrhosis only and 100 non‐cirrhotic controls. We compared pre‐diagnostic plasma levels of 102 markers in HCC cases to non‐cirrhotic and cirrhotic controls using polytomous logistic regression. A priori markers included insulin‐like growth factor binding protein‐3 (IGFBP‐3), intercellular adhesion molecule 1 (ICAM‐1) and interleukin 6 (IL‐6). P‐values for other markers were corrected for multiple testing (false discovery rate = 10%). Results: In both REVEAL‐HBV and REVEAL‐HCV, increasing levels of ICAM‐1 were associated with increased risk of HCC compared to non‐cirrhotic controls (P‐trend 0.02 and 0.001, respectively). In both REVEAL‐HBV and REVEAL‐HCV, two novel markers [C‐X‐C motif chemokine 11 (CXCL11) and hepatocyte growth factor (HGF)] were positively associated [strongest odds ratioquartile 4 versus 1 (OR) 4.55 for HGF in HCV], while two [complement factor H related 5 (CFHR5) and stem cell factor (SCF)] were negatively associated (strongest ORQ4vQ1 0.14 for SCF in HCV) with development of HCC compared to non‐cirrhotic controls. Conclusions: We confirmed the association for ICAM‐1 and identified 4 additional proteins associated with HBV‐ and HCV‐related HCC. These findings highlight the importance of immunologic processes in HBV‐ and HCV‐related HCC. [ABSTRACT FROM AUTHOR]

Aim: Larger tumour size and lymph node involvement traditionally predict poorer survival in colon cancer patients. However, it has been recently suggested that very small tumours (<5 mm) may be a predictor of poor prognosis in colon cancer patients when lymph nodes are involved. This study investigated whether node‐positive colon cancer patients with small tumours had worse survival compared to those with larger tumours in the Department of Defense's (DoD) Military Health System (MHS), a universal health care system. Methods: Surgically treated colon cancer patients were identified from the DoD's Automated Central Tumour Registry (ACTUR). These patients were diagnosed with Stage I–III colon cancer between 1989 and 2010, had one or more lymph nodes examined, did not receive pre‐operative radiotherapy and were followed through 2013 to determine vital status. Multivariable Cox models were used to examine survival differences according to tumour size, and data were stratified by lymph node status and age. Results: There were no differences in overall survival according to tumour size in the study population. These findings remained similar in analyses stratified by lymph node status and age. Conclusion: In a universal healthcare system, small tumour size is not associated with worse prognosis in node‐positive colon cancer patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions. Materials & Methods: The analysis included 424 participants from a cross‐sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. Results: No overall associations between H pylori,H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. Conclusions: While no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the dominant histologic type of liver cancer, accounting for 75% of cases. Growing evidence suggests that the cross‐talk between the gut microbiome and metabolome (ie, gut‐liver axis) are related to the development of hepatic inflammation, and ultimately, HCC. Bile acids are metabolites, derived from cholesterol and synthesized in the liver, which may have a critical role in regulation of the gut‐liver axis. We investigated whether prediagnostic circulating bile acids were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)‐Hepatitis B Virus (HBV) and REVEAL‐Hepatitis C Virus (HCV) cohorts from Taiwan. Fifteen bile acids were quantitated using liquid chromatography, from 185 cases and 161 matched controls in REVEAL‐HBV and 96 cases and 96 matched controls in REVEAL‐HCV. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between bile acid levels and HCC were calculated using multivariable‐adjusted logistic regression. Higher levels of glycine and taurine conjugated primary bile acids were associated with a 2‐ to 8‐fold increased risk of HBV‐ (eg, glycocholic acid ORQ4vsQ1 = 3.38, 95% CI: 1.48‐7.71, Ptrend <.003) and HCV‐related HCC (eg, OR = 8.16, 95% CI: 2.21‐30.18, Ptrend <.001). However, higher levels of the secondary bile acid deoxycholic acid were inversely associated with HBV‐related HCC risk (OR = 0.41, 95% CI: 0.19‐0.88, Ptrend =.02). Our study provides evidence that higher concentrations of bile acids—specifically, conjugated primary bile acids—are associated with increased HCC risk. However, our study does not support the hypothesis that higher levels of secondary bile acids increase liver cancer risk; indeed, deoxycholic acid may be associated with a decreased HCC risk. What's new? The bacteria in the gut convert bile acids into secondary bile acids. In rodents, these acids increase the risk of hepatocellular carcinoma (HCC). In this study, however, the authors found that the same does not apply to humans. Instead, primary bile acids are associated with an increased risk, at least in patients with hepatitis B or C viral infection. Secondary bile acids, such as deoxycholic acid, may even decrease HCC risk. The human microbiome is intricately linked with hepatic metabolic processes, known as the gut‐liver axis, and the present study highlights the need to examine this cross‐talk between the microbiome and metabolome. [ABSTRACT FROM AUTHOR]

Deficient intake of micronutrients involved in one‐carbon metabolism (eg, choline, methionine, vitamin B12 and folic acid) leads to hepatocellular carcinoma (HCC) development in rodents, but is under‐investigated in humans. We investigated the association between one‐carbon metabolism‐related micronutrient intake and HCC risk in a prospective cohort of 494 860 participants with 16 years of follow‐up in the NIH‐AARP study. Dietary intakes and supplement use were ascertained at baseline using a food‐frequency questionnaire. Total intake (diet plus supplements) of the following one‐carbon metabolism‐related micronutrients were calculated: folate, methionine and vitamins B2 (riboflavin), B3 (niacin), B6 and B12. These micronutrients were examined both individually and simultaneously, with adjustment for covariates. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over the 16‐year follow‐up period, 647 incident HCC cases were diagnosed. When examined individually, higher total vitamin B3 intake was associated with a lower HCC risk (HRQ5 vs Q1 = 0.60; 95% CI = 0.42‐0.85; Ptrend =.008), and the association remained significant when all six micronutrients were examined simultaneously (HRQ5 vs Q1 = 0.32; 95% CI = 0.18‐0.55; Ptrend <.0001). Among participants with >3 years of follow‐up, higher total vitamin B3 intake was again associated with lower risk (HRQ5 vs Q1 = 0.37; 95% CI = 0.20‐0.68; Ptrend =.001), whereas higher total vitamin B6 intake was associated with higher risk (HRQ5 vs Q1 = 2.04; 95% CI = 1.02‐4.07; Ptrend =.04). Restricted cubic spline analyses showed a dose‐response inverse association between total vitamin B3 intake and HCC risk, and dose‐response positive association between total vitamin B6 intake and HCC risk. The study suggests that higher vitamin B3 intake is associated with lower HCC risk, whereas higher vitamin B6 intake is associated with increased risk. What's new? Dietary micronutrients such as methionine and B vitamins are critical for DNA methylation, owing to methyl groups derived via one‐carbon metabolism. In the liver, deficiency of these methyl donors leads to hypomethylation and altered gene expression, potentially fueling hepatic tumorigenesis. Here, comprehensive investigation of one‐carbon metabolism‐related micronutrient intake and risk of hepatocellular carcinoma (HCC) shows that relatively high vitamin B3 intake is associated with reduced HCC risk. By comparison, elevated vitamin B6 intake was linked to increased HCC risk. The findings suggest that dietary modifications emphasizing healthy vitamin B3 intake while limiting vitamin B6 levels could enhance HCC prevention strategies. [ABSTRACT FROM AUTHOR]

In the United States, hepatocellular carcinoma (HCC) survival varies with tumor characteristics, patient comorbidities, and treatment. The effect of HCC etiology on survival is less clearly defined. The relationship between HCC etiology and mortality was examined using Surveillance, Epidemiology, and End Results–Medicare data. In a cohort of 11,522 HCC cases diagnosed from 2000 through 2014, etiologies were identified from Medicare data, including metabolic disorders (32.9%), hepatitis C virus (8.2%), alcohol (4.7%), hepatitis B virus (HBV, 2.1%), rare etiologies (0.9%), multiple etiologies (26.7%), and unknown etiology (24.4%). After adjusting for demographics, tumor characteristics, comorbidities and treatment, hazard ratios (HRs) and survival curves by HCC etiology were estimated using Cox proportional hazard models. Compared with HBV‐related HCC cases, higher mortality was observed for those with alcohol‐related HCC (HR 1.49; 95% confidence interval [95% CI] 1.25‐1.77), metabolic disorder–related HCC (HR 1.25; 95% CI 1.07‐1.47), and multiple etiology‐related HCC (HR 1.25; 95% CI 1.07‐1.46), but was not statistically significant for hepatitis C virus–related, rare disorder–related, and HCC of unknown etiology. For all HCC etiologies, there was short median survival ranging from 6.1 months for alcohol to 10.3 months for HBV. Conclusion: More favorable survival was seen with HBV‐related HCC. To the extent that HCC screening is more common among persons with HBV infection compared to those with other etiologic risk factors, population‐based HCC screening, applied evenly to persons across all HCC etiology categories, could shift HCC diagnosis to earlier stages, when cases with good clinical status are more amenable to curative therapy. [ABSTRACT FROM AUTHOR]

Testicular cancer is the most common cancer among young men of European ancestry, with about one‐third of all cases occurring in Europe. With the historically increasing trends in some high‐incidence populations reported to have stabilised in recent years, we aimed to assess recent trends and predict the future testicular cancer incidence burden across Europe. We extracted testicular cancer (ICD‐10 C62) incidence data from Cancer Incidence in Five Continents Volumes VII–XI and complemented this with data published by registries from 28 European countries. We predicted cancer incidence rates and the number of incident cases in Europe in the year 2035 using the NORDPRED age‐period‐cohort model. Testicular cancer incidence rates will increase in 21 out of 28 countries over the period 2010–2035, with trends attenuating in the high‐incidence populations of Denmark, Norway, Switzerland and Austria. Although population ageing would be expected to reduce the number of cases, this demographic effect is outweighed by increasing risk, leading to an overall increase in the number of cases by 2035 in Europe, and by region (21, 13 and 32% in Northern, Western and Eastern Europe, respectively). Declines are however predicted in Italy and Spain, amounting to 12% less cases in 2035 in Southern Europe overall. In conclusion, the burden of testicular cancer incidence in Europe will continue to increase, particularly in historically lower‐risk countries. The largest increase in the number of testicular cancer patients is predicted in Eastern Europe, where survival is lower, reinforcing the need to ensure the provision of effective treatment across Europe. What's new? Testicular cancer (TC) is the most common cancer among young men of European ancestry. As the population ages, will rates of TC decrease? In this study, the authors found that, on the contrary, TC risk is predicted to rise in many European countries through the year 2035. The largest increase in the number of TC patients (32%) is predicted in Eastern Europe, where survival is also lower. These results reinforce the need to ensure that effective treatment is provided throughout Europe. [ABSTRACT FROM AUTHOR]

Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population‐based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5‐year period, age‐standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South‐East, and Italy. However, rates in these high‐risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high‐risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high‐rate, as well as low‐rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer‐term. What's new? A new analysis of worldwide trends reveals that, between 1978 and 2012, liver cancer rates fell in east Asia and Italy, but rose in India, Europe, and the Americas. In this report, the authors analyzed 35 years of liver cancer incidence, the second leading cause of cancer death worldwide. Using data from the CI5plus database, they calculated incidence rates for 5 year intervals. Although liver cancer rates remained high in east Asia and Italy, they decreased, and are expected to continue to decline as HBV prevalence declines. However, liver cancer rates rose elsewhere, possibly due to increased obesity and diabetes. [ABSTRACT FROM AUTHOR]

Background: Glioma is the most common malignant brain cancer. Accessibility to health care is an important factor affecting cancer outcomes in the US general population. The US Military Health System (MHS) provides universal health care to its beneficiaries. It is unknown whether this universal health care has translated into improved survival outcomes among MHS beneficiaries with glioma. This study compared the overall survival of patients with glioma in the MHS with the overall survival of patients with glioma in the general population.Methods: The MHS cases were identified from the Department of Defense's Automated Central Tumor Registry (ACTUR). Glioma cases from the general population were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. SEER cases were matched 2:1 to ACTUR cases by age, sex, race, histology, and diagnosis year. All cases had histologically confirmed glioma diagnosed between January 1, 1987, and December 31, 2013. A Kaplan-Meier analysis was conducted to compare survival between the ACTUR and SEER cases. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: The study included 2231 glioma cases from ACTUR and 4462 cases from SEER. ACTUR cases exhibited significantly better overall survival than SEER cases (HR, 0.74; 95% CI, 0.67-0.83). The survival advantage of the ACTUR patients was observed in most subgroups stratified by age, sex, race, diagnosis year, and histology. For glioblastoma, the survival advantage was observed in both the pre- and post-temozolomide periods.Conclusions: Universal MHS health care may have translated into improved survival outcomes in glioma. Future studies are warranted to identify factors contributing to the improved survival. [ABSTRACT FROM AUTHOR]

Background: Liver cancer incidence has increased for several decades in the United States. Recently, reports have suggested that rates of hepatocellular carcinoma (HCC), the dominant form of liver cancer, had declined in certain groups. However, to the authors' knowledge, the most recent histology‐specific liver cancer rates have not been reported to date. Methods: The authors examined the incidence of HCC and intrahepatic cholangiocarcinoma (ICC) from 1992 through 2016 using data from the Surveillance, Epidemiology, and End Results registries. Age‐standardized incidence rates were calculated by histology, sex, race and/or ethnicity, and age. Trends were analyzed using the National Cancer Institute's Joinpoint Regression Program to estimate the annual percent change. Results: Between 2011 and 2016, HCC rates significantly declined (annual percent change, −1.9%), with more prominent declines noted among males, Asian/Pacific Islanders, and individuals aged <50 years. Conversely, ICC rates increased from 2002 through 2016. Conclusions: Declining HCC rates may persist due to improved treatment of the hepatitis C virus and/or competing causes of mortality among individuals with fatty liver disease. Between 2011 and 2016, rates of hepatocellular carcinoma are noted to have significantly declined (annual percent change, −1.9%), driven by declines among males, Asian/Pacific Islanders, and individuals aged <50 years. Conversely, intrahepatic cholangiocarcinoma rates have been found to have increased from 2002 through 2016. [ABSTRACT FROM AUTHOR]

Background and aims: Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1‐signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. Methods: Formalin‐fixed, paraffin‐embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer‐related genes was sequenced in the RNAlater samples. Results: Ninety‐one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51‐70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1‐signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. Conclusions: The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database.Methods: Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios.Results: The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.80; ASR for ECC, 2.24), Thailand (ASR for ICC, 2.19; ASR for ECC, 0.71), and Japan (ASR for ICC, 0.95; ASR for ECC, 0.83). Between 1993 and 2012, incidence rates of both ICC and ECC increased in most countries. The largest ASR increases over the study period occurred in Latvia (AAPC, 20.1%) and China (AAPC, 11.1%) for ICC and in Thailand (AAPC, 8.8%) and Colombia (AAPC, 8.5%) for ECC.Conclusions: In the 20 years examined, ICC and ECC incidence increased in the majority of countries worldwide. ICC and ECC incidence may continue to increase because of metabolic and infectious etiologic factors. Efforts to further elucidate risk factors contributing to these increases in incidence are warranted. [ABSTRACT FROM AUTHOR]

Background and Aim: The incidence of hepatocellular carcinoma (HCC) has risen considerably in the US since 1980. The main causes include metabolic disorders (NAFLD, diabetes, obesity, metabolic syndrome), alcohol‐related disease (ALD) and hepatitis C and B virus infections (HCV, HBV). Etiology‐specific HCC incidence rates by detailed race‐ethnicity are needed to improve HCC control and prevention efforts. Methods: All HCC cases diagnosed in Florida during 2014‐2015 were linked to statewide hospital discharge data to determine etiology. Age‐specific and age‐adjusted rates were used to assess the intersection between etiology and detailed racial‐ethnicities, including White, African American, Afro‐Caribbean, Asian, Cuban, Puerto Rican and Continental Hispanic (Mexican, South and Central American). Results: Of 3666 HCC cases, 2594 matched with discharge data. HCV was the leading cause of HCC among men and women (50% and 43% respectively), followed by metabolic disorders (25% and 37%) and ALD (16% and 9%). Puerto Rican and African American men had the highest HCV‐HCC rates, 7.9 and 6.3 per 100 000 respectively. Age‐specific rates for HCV‐HCC peaked among baby boomers (those born in 1945‐1965). Metabolic‐HCC rates were highest among populations above age 70 and among Continental Hispanics. Afro‐Caribbean men had high rates of HBV‐HCC, whereas Puerto Rican men had high ALD‐HCC. Conclusions: HCC etiology is associated with specific race/ethnicity. While HCV‐related HCC rates are projected to decrease soon, HCC will continue to affect Hispanics disproportionately, based on higher rates of metabolic‐HCC (and ALD‐HCC) among Continental Hispanics, who demographically represent 80% of all US Hispanics. Multifaceted approaches for HCC control and prevention are needed. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association between comorbidities and stage at diagnosis among NSCLC patients in the US Military Health System (MHS), which provides universal health care to its beneficiaries.Methods: The linked data from the Department of Defense's Central Cancer Registry (CCR) and the MHS Data Repository (MDR) were used. The study included 4768 patients with histologically confirmed primary NSCLC. Comorbid conditions were extracted from the MDR data. Comorbid conditions were those included in the Charlson Comorbidity Index (CCI) and were defined as a diagnosis during a 3-year time frame prior to the NSCLC diagnosis. Multivariable logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) of late stage (stages III and IV) versus early stage (stages I and II) in relation to pre-existing comorbidities.Results: Compared to patients with no comorbidities, those with prior comorbidities tended to be less likely to have lung cancer diagnosed at late stage. When specific comorbidities were analyzed, decreased odds of being diagnosed at late stage were observed among those with chronic obstructive pulmonary disease (COPD) (adjusted OR 0.78, 95% CI 0.68 to 0.90). In contrast, patients with a congestive heart failure or a liver cirrhosis/chronic hepatitis had an increased likelihood of being diagnosed at late stage (adjusted OR 1.30, 95% CI 1.00 to 1.69 and adjusted OR 1.87, 95% CI 1.24 to 2.82, respectively).Conclusions: Among NSCLC patients in an equal access health system, the likelihood of late stage at diagnosis differed by specific comorbid diseases. [ABSTRACT FROM AUTHOR]

Purpose To report age-specific serum estradiol concentration in nonsmoking, lean US men without comorbidities. We provide concentrations from 30 and 15 to 20 years ago given previously described declines in serum estradiol in US men over time. Methods We used data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988 to 1991) and continuous NHANES (1999 to 2004). Serum estradiol and SHBG were previously measured by competitive electrochemiluminescence immunoassays. Free estradiol was estimated from estradiol, SHBG, and albumin. By age, we calculated median concentrations overall and for nonsmoking, lean (body mass index <25 kg/m2 and waist <102 cm) men without diabetes, cardiovascular disease, or cancer. Results Overall, respective total estradiol medians for men ages 20 to 39, 40 to 59, and ≥60 years old were 37.0, 33.9, and 33.5 pg/mL in NHANES III and 31.3, 30.5, and 27.0 pg/mL in continuous NHANES. In nonsmoking, lean men without comorbidities, respective total estradiol medians were 32.0, 32.1, and 32.0 pg/mL in NHANES III and 29.1, 22.7, and 26.1 pg/mL in continuous NHANES. Overall, respective free estradiol medians were 0.82, 0.72, and 0.64 pg/mL in NHANES III and 0.67, 0.61, and 0.47 pg/mL in continuous NHANES. In nonsmoking, lean men without comorbidities, respective free estradiol medians were 0.64, 0.67, and 0.62 pg/mL in NHANES III and 0.58, 0.42, and 0.40 pg/mL continuous NHANES. Conclusion We report US nationally representative serum estradiol concentrations in healthy men, which could be used for targeting estradiol during testosterone supplementation and for general good health. [ABSTRACT FROM AUTHOR]

Context Testosterone deficiency prevalence increases with age, comorbidities, and obesity. Objective To inform clinical guidelines for testosterone deficiency management and development of targets for nonpharmacologic intervention trials for these men, we determined serum testosterone in never-smoking, lean men without select comorbidities in nationally representative surveys. Design, Setting, Participants We used cross-sectional data for never-smoking, lean men ≥20 years without diabetes, myocardial infarction, congestive heart failure, stroke, or cancer, without use of hormone-influencing medications, and participated in morning sessions of National Health and Nutrition Examination Survey (NHANES) III (phase I 1988–1991) or continuous NHANES (1999–2004). By age, we determined median total testosterone (ng/mL) measured previously by a Food and Drug Administration-approved immunoassay and median estimated free testosterone concentration. Results In NHANES III, in never-smoking, lean men without comorbidities, median (25th, 75th percentile) testosterone was 4% to 9% higher than all men—20 to 39 years: 6.24 (5.16, 7.51), 40 to 59: 5.37 (3.83, 6.49), and ≥60: 4.61 (4.01, 5.18). In continuous NHANES, in never-smoking, lean men without comorbidities, levels were 13% to 24% higher than all men—20 to 39 years: 6.26 (5.32, 7.27), 40 to 59: 5.86 (4.91, 6.55), and ≥60: 4.22 (3.74, 5.73). In never-smoking, lean men without comorbidities, median estimated free testosterone was similar to (NHANES III) or slightly higher than (continuous NHANES) in all men. Conclusions These nationally representative data document testosterone levels (immunoassay) in never-smoking, lean men without select comorbidities 30 and 15 to 20 years ago. This information can be incorporated into guidelines for testosterone deficiency management and used to develop targets for nonpharmacologic intervention trials for testosterone deficiency. [ABSTRACT FROM AUTHOR]

Purpose: Periodontal disease, a major cause of tooth loss in adults, may have systemic effects and has been associated with higher risk of several cancer types. However, the associations of periodontal disease or tooth loss with liver cancer have only been examined prospectively in two studies, neither of which had sufficient statistical power. In addition, no studies assessed the potential confounding by viral hepatitis or Helicobacter pylori infection status.Methods: In this study, we examined the association between tooth loss and primary liver cancer incidence in a prospective cohort of Finnish male smokers (n = 29,096). We used Cox proportional hazards models to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs. As a sensitivity analysis, we conducted a nested case-control study within the original cohort to assess confounding by hepatitis B or C virus infection and seropositivity of H. pylori.Results: A total of 213 incident primary liver cancers occurred during a mean follow-up of 17 years. Among these cases, having 11-31 permanent teeth lost (HR 1.42, 95% CI 1.01-1.98) or all 32 teeth lost (HR 1.45, 95% CI 1.00-2.10) was each associated with higher risk of liver cancer, compared to those having 0-10 teeth lost. Adjusting for H. pylori seropositivity yielded a small attenuation of the effect estimate.Conclusions: Greater number of teeth lost was associated with higher risk of primary liver cancer in our study. The role of periodontal infection in the development of liver cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

Incidence of non-alcoholic fatty liver disease (NAFLD) and liver cancer are 2–3 times higher in males than females. Hormonal mechanisms are hypothesized, with studies suggesting that oophorectomy may increase risk, but population-based evidence is limited. Thus, we conducted a study within the Clinical Practice Research Datalink, with controls matched to cases of NAFLD (n = 10,082 cases/40,344 controls) and liver cancer (n = 767 cases/3068 controls). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Effect measure modification by menopausal hormone therapy (MHT) was examined, using likelihood ratio tests and relative excess risk due to interaction (RERI). Oophorectomy was associated with a 29% elevated NAFLD risk (OR = 1.29, 95% CI 1.18–1.43), which was more pronounced in women without diabetes (OR = 1.41, 95% CI 1.27–1.57) and in women who had oophorectomy prior to age 50 (OR = 1.37, 95% CI 1.22–1.52). Compared to women without oophorectomy or MHT use, oophorectomy and MHT were each associated with over 50% elevated risk of NAFLD. However, the combination of oophorectomy and MHT showed evidence of a negative interaction on the multiplicative (p = 0.003) and additive scales (RERI = − 0.28, 95% CI − 0.60 to 0.03, p = 0.08). Oophorectomy, overall, was not associated with elevated liver cancer risk (OR = 1.16, 95% CI 0.79–1.69). These findings suggest that oophorectomy may increase the risk of NAFLD, but not liver cancer. [ABSTRACT FROM AUTHOR]