Publications by authors named "Katherine A McGlynn"

256 Publications

Immunologic markers and risk of hepatocellular carcinoma in hepatitis B virus- and hepatitis C virus-infected individuals.

Aliment Pharmacol Ther 2021 Jul 19. Epub 2021 Jul 19.

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

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 ratio (OR) 4.55 for HGF in HCV], while two [complement factor H related 5 (CFHR5) and stem cell factor (SCF)] were negatively associated (strongest OR 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.
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http://dx.doi.org/10.1111/apt.16524DOI Listing
July 2021

Comparison of Survival among Colon Cancer Patients in the U.S. Military Health System and Patients in the Surveillance, Epidemiology, and End Results (SEER) Program.

Cancer Epidemiol Biomarkers Prev 2021 Jul 23;30(7):1359-1365. Epub 2021 Jun 23.

John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, Maryland.

Background: Access to health care is associated with cancer survival. The U.S. military health system (MHS) provides universal health care to beneficiaries, reducing barriers to medical care access. However, it is unknown whether the universal care has translated into improved survival among patients with colon cancer. We compared survival of patients with colon cancer in the MHS to that in the U.S. general population and assessed whether stage at diagnosis differed between the two populations and thus could contribute to survival difference.

Methods: The data were from Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR) and the NCI's Surveillance, Epidemiology, and End Results (SEER) program, respectively. The ACTUR ( = 11,907) and SEER patients ( = 23,814) were matched to demographics and diagnosis year with a matching ratio of 1:2. Multivariable Cox regression model was used to estimate all-cause mortality for ACTUR compared with SEER.

Results: ACTUR patients exhibited better survival than their SEER counterparts (HR, 0.82; 95% confidence interval, 0.79-0.87) overall and in most subgroups by age, in both men and women, and in whites and blacks. The better survival remained when the comparison was stratified by tumor stage.

Conclusions: Patients with colon cancer in a universal health care system had better survival than patients in the general population.

Impact: Universal care access is important to improve survival of patients with colon cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1267DOI Listing
July 2021

Histological Features of Sporadic and Familial Testicular Germ Cell Tumors Compared and Analysis of Age-Related Changes of Histology.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.

This study aimed to compare histological features of familial and sporadic testicular germ cell tumors (TGCTs) and surrounding parenchyma, since discriminating features might be etiologically relevant and clinically useful. The study of parenchyma was prompted by reports claiming a higher prevalence of testicular microlithiasis in familial cases. Histological features of TGCTs and surrounding parenchyma of 296 sporadic and 305 familial cases were compared. For each case, one representative hematoxylin and eosin-stained slide was available. Slides were independently scored by two expert pathologists using a semi-quantitative data abstract. Discrepancies were resolved by consensus. A logistic regression model was used to assess the ability to discriminate between sporadic and familial GCT. The histological composition of a tumor, amount of lymphocytic infiltration, amount of germ cell neoplasia in situ (GCNIS), and presence of testicular microlithiasis (TM) did not discriminate between sporadic and familial GCT (area under the curve 0.56, 95%CI 0.51-0.61). Novel observations included increasing lymphocytic infiltration and decreasing GCNIS and TM with increasing age at diagnosis. The presence of tubules with infiltrating lymphocytes was mainly associated with pure seminomas and nonseminomas with a seminoma component. Among seminomas, tubules with infiltrating lymphocytes decreased with increasing age. No discernable differences between sporadic and familial TGCTs were found. The age-related changes in the tumors and surrounding parenchyma in these groups combined are consistent with a host response building up over time predominantly affecting seminomas, the seminoma-component of nonseminomas and GCNIS. TM may gradually dissolve with age. Our hypothesis that histological differences between sporadic and familial TGCT might identify genetically distinct disease subsets was not supported.
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http://dx.doi.org/10.3390/cancers13071652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037944PMC
April 2021

Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk.

Cancer Epidemiol Biomarkers Prev 2021 Jun 18;30(6):1275-1278. Epub 2021 Mar 18.

Division of Cancer Epidemiology and Genetics, NCI, Rockville, Maryland.

Background: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results.

Methods: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk.

Results: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97-1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls).

Conclusions: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk.

Impact: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172526PMC
June 2021

Breast cancer mortality trends in Peruvian women.

BMC Cancer 2020 Dec 1;20(1):1173. Epub 2020 Dec 1.

Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20133, Milan, Italy.

Background: Breast cancer (BC) is the most common malignancy in Latin American women, but with a wide variability with respect to their mortality. This study aims to estimate the mortality rates from BC in Peruvian women and to assess mortality trends over 15 years.

Methods: We calculated BC age-standardized mortality rate (ASMR) per 100,000 women-years using the world standard SEGI population. We estimated joinpoint regression models for BC in Peru and its geographical areas. The spatial analysis was performed using the Moran's I statistic.

Results: In a 15-year period, Peru had a mortality rate of 9.97 per 100,000 women-years. The coastal region had the highest mortality rate (12.15 per 100,000 women-years), followed by the highlands region (4.71 per 100,000 women-years). In 2003, the highest ASMR for BC were in the provinces of Lima, Arequipa, and La Libertad (above 8.0 per 100,000 women-years), whereas in 2017, the highest ASMR were in Tumbes, Callao, and Moquegua (above 13.0 per women-years). The mortality trend for BC has been declining in the coastal region since 2005 (APC = - 1.35, p < 0.05), whereas the highlands region experienced an upward trend throughout the study period (APC = 4.26, p < 0.05). The rainforest region had a stable trend. Spatial analysis showed a Local Indicator of Spatial Association of 0.26 (p < 0.05).

Conclusion: We found regional differences in the mortality trends over 15 years. Although the coastal region experienced a downward trend, the highlands had an upward mortality trend in the entire study period. It is necessary to implement tailored public health interventions to reduce BC mortality in Peru.
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http://dx.doi.org/10.1186/s12885-020-07671-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706041PMC
December 2020

Agreement Between the Prevalence of Nonalcoholic Fatty Liver Disease Determined by Transient Elastography and Fatty Liver Indices.

Clin Gastroenterol Hepatol 2020 Nov 20. Epub 2020 Nov 20.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) is a global public health problem linked to the rising prevalence of obesity and metabolic disorders. Accurate estimates of NAFLD in populations are challenging because the gold standard for detection is liver biopsy, an invasive procedure that precludes its use in research settings. NAFLD can also be detected via noninvasive imaging, such as ultrasound, magnetic resonance imaging-determined proton density fat fraction, magnetic resonance spectroscopy, and the controlled attenuation parameter derived via transient elastography (CAP-TE). Given the complexities of imaging in population studies, however, many estimates have been based on calculated indices, such as the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Concern has been raised that the indices underestimate the prevalence of NAFLD, thus downplaying the scope of the public health challenge. Ability to examine whether these concerns are substantive has been provided by a recent study of the US population. Using data from the study, it was reported that the US prevalence of CAP-TE-determined NAFLD was 47.8%. The current analysis used data from the same national study to examine how well the fatty liver indices corresponded to CAP-TE-determined NAFLD. Because most persons with NAFLD reportedly have elevated alanine aminotransferase (ALT) levels, the correspondence between elevated ALT and CAP-TE was also examined.
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http://dx.doi.org/10.1016/j.cgh.2020.11.028DOI Listing
November 2020

Leukemia mortality in children from Latin America: trends and predictions to 2030.

BMC Pediatr 2020 11 7;20(1):511. Epub 2020 Nov 7.

Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru.

Background: Reports suggest that Latin American and Caribbean (LAC) countries have not reduced leukemia mortality compared to high-income countries. However, updated trends remain largely unknown in the region. Given that leukemia is the leading cause of cancer-related death in LAC children, we evaluated mortality trends in children (0-14y) from 15 LAC countries for the period 2000-2017 and predicted mortality to 2030.

Methods: We retrieved cancer mortality data using the World Health Organization Mortality Database. Mortality rates (standardized to the world standard SEGI population) were analyzed for 15 LAC countries. We evaluated the average mortality rates for the last 5 years (2013-2017). Joinpoint regression analysis was used to evaluate leukemia mortality trends and provide an estimated annual percent change (EAPC). Nordpred was utilized for the calculation of predictions until 2030.

Results: Between 2013 and 2017, the highest mortality rates were reported in Venezuela, Ecuador, Nicaragua, Mexico, and Peru. Upward mortality trends were reported in Nicaragua (EAPC by 2.9% in boys, and EAPC by 2.0% in girls), and Peru (EAPC by 1.4% in both sexes). Puerto Rico experienced large declines in mortality among both boys (EAPC by - 9.7%), and girls (EAPC by - 6.0%). Leukemia mortality will increase in Argentina, Ecuador, Guatemala, Panama, Peru, and Uruguay by 2030.

Conclusion: Leukemia mortality is predicted to increase in some LAC countries by 2030. Interventions to prevent this outcome should be tailor to reduce the socioeconomic inequalities and ensure universal healthcare coverage.
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http://dx.doi.org/10.1186/s12887-020-02408-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648388PMC
November 2020

Hepatocellular Carcinoma Survival by Etiology: A SEER-Medicare Database Analysis.

Hepatol Commun 2020 Oct 9;4(10):1541-1551. Epub 2020 Aug 9.

Division of Cardiovascular Science National Heart, Lung and Blood Institute National Institutes of Health Bethesda MD.

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. 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.
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http://dx.doi.org/10.1002/hep4.1564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527688PMC
October 2020

Associations between Helicobacter pylori with nonalcoholic fatty liver disease and other metabolic conditions in Guatemala.

Helicobacter 2020 Dec 2;25(6):e12756. Epub 2020 Oct 2.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

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.
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http://dx.doi.org/10.1111/hel.12756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688101PMC
December 2020

Tumour size and overall survival among surgically treated patients with non-metastatic colon cancer in the U.S. Military Health System.

Colorectal Dis 2021 Jan 27;23(1):192-199. Epub 2020 Oct 27.

Department of Surgery, John P. Murtha Cancer Center Research Program, Walter Reed National Military Medical Center, Uniformed Service University of the Health Sciences, Bethesda, MD, USA.

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.
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http://dx.doi.org/10.1111/codi.15381DOI Listing
January 2021

Challenges in elucidating cholangiocarcinoma etiology.

Hepatobiliary Surg Nutr 2020 Aug;9(4):537-539

Slone Epidemiology Center, Boston University, Boston, MA, USA.

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http://dx.doi.org/10.21037/hbsn.2020.02.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423558PMC
August 2020

Aflatoxin B exposure and liver cirrhosis in Guatemala: a case-control study.

BMJ Open Gastroenterol 2020 07;7(1)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Objective: In Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis B virus, hepatitis C virus and heavy alcohol consumption, appears to be low. Aflatoxin B (AFB) exposure, however, appears to be high, and thus could be associated with the high burden of cirrhosis. Whether AFB increases the risk of cirrhosis in the absence of viral infection, however, is not clear.

Design: Cirrhosis cases (n=100) from two major referral hospitals in Guatemala City were compared with controls (n=200) from a cross-sectional study. Logistic regression was used to estimate the ORs and 95% CIs of cirrhosis and quintiles of AFB in crude and adjusted models. A sex-stratified analysis was also conducted.

Results: The median AFB level was significantly higher among the cases (11.4 pg/mg) than controls (5.11 pg/mg). In logistic regression analyses, higher levels of AFB was associated with cirrhosis (quintile 5 vs quintile 1, OR: 11.55; 95% CI 4.05 to 32.89). No attenuation was observed with adjustment by sex, ethnicity, hepatitis B virus status, and heavy alcohol consumption. A significantly increasing trend in association was observed in both models (p trend <0.01). Additionally, the cirrhosis-AFB association was more prominent among men.

Conclusions: The current study found a significant positive association between AFB exposure and cirrhosis. Mitigation of AFB exposure and a better understanding of additional risk factors may be important to reduce the burden of cirrhosis in Guatemala.
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http://dx.doi.org/10.1136/bmjgast-2020-000380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342465PMC
July 2020

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Nat Commun 2020 07 3;11(1):3353. Epub 2020 Jul 3.

Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
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http://dx.doi.org/10.1038/s41467-020-16483-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335068PMC
July 2020

Seropositivity for Helicobacter pylori and hepatobiliary cancers in the PLCO study.

Br J Cancer 2020 09 29;123(6):909-911. Epub 2020 Jun 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Helicobacter has been suggested to play a possible role in hepatitis, gallstones, and hepatobiliary tumours. We assessed whether seropositivity to 15 H. pylori proteins was associated with subsequent incidence of 74 biliary tract and 105 liver cancer cases vs. 357 matched controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Odds ratios and 95% confidence intervals were computed by conditional logistic regression after adjustment for known hepatobiliary cancer risk factors. H. pylori seropositivity was not associated with either biliary tract (1.76, 0.90-3.46) or liver cancer (0.87, 0.46-1.65). CagA seropositivity was associated with both endpoints, although the latter association was not statistically significant (biliary tract: 2.16, 1.03-4.50; liver cancer: 1.96, 0.98-3.93) and neither association was statistically significant after correcting for multiple comparisons. Together, these results suggest possible associations between H. pylori and hepatobiliary cancer and suggest the value of future studies investigating the association.Trial registration number: NCT00339495.
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http://dx.doi.org/10.1038/s41416-020-0961-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493958PMC
September 2020

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

J Hepatol 2020 10 11;73(4):863-872. Epub 2020 May 11.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.

Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.

Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.

Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.

Lay Summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
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http://dx.doi.org/10.1016/j.jhep.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901003PMC
October 2020

Relationship of sex steroid hormones with bone mineral density of the lumbar spine in adult men.

Bone Joint Res 2020 Mar 16;9(3):139-145. Epub 2020 May 16.

Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

Aims: To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA.

Methods: Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity.

Results: Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity.

Conclusion: In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. 2020;9(3):139-145.
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http://dx.doi.org/10.1302/2046-3758.93.BJR-2019-0141.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229310PMC
March 2020

Prediagnostic concentrations of circulating bile acids and hepatocellular carcinoma risk: REVEAL-HBV and HCV studies.

Int J Cancer 2020 11 8;147(10):2743-2753. Epub 2020 Jun 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

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 OR = 3.38, 95% CI: 1.48-7.71, P < .003) and HCV-related HCC (eg, OR = 8.16, 95% CI: 2.21-30.18, P < .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, P = .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.
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http://dx.doi.org/10.1002/ijc.33051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529994PMC
November 2020

Increasing Incidence of Testicular Germ Cell Tumors among Racial/Ethnic Minorities in the United States.

Cancer Epidemiol Biomarkers Prev 2020 06 8;29(6):1237-1245. Epub 2020 May 8.

National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

Background: The incidence of testicular germ cell tumors (TGCT) has been rising in the United States and is notably higher among white men. Previously, our group reported that rates were rising among Hispanic men in certain areas. This study sought to determine whether the patterns noted in our prior publication remained evident in more recent years and to determine whether any new patterns have emerged.

Methods: Data from 51 U.S. cancer registries were examined. Racial/ethnic-specific incidence rates per 100,000 man-years were calculated overall and by census region. Annual percent changes (APC) were estimated, and joinpoint models were fit. Differences in regional incidence were examined using the Wald test.

Results: During the time period 2001 to 2016, 126,575 TGCTs were recorded. TGCT incidence was highest among non-Hispanic whites (NHW; 6.63/100,000), followed by Hispanics (4.20), American Indian/Alaska Natives (AI/AN; 3.27), Asian/Pacific Islanders (A/PI; 1.72), and non-Hispanic blacks (NHB; 1.27). TGCT incidence increased significantly among all men; the greatest increase was experienced by A/PIs (APC: 2.47), followed in order by Hispanics (2.10), AI/ANs (1.71), NHBs (1.28), and NHWs (0.41). Significant differences in rates by region were seen for all men except NHBs, with the highest rates among Hispanics (5.38/100,000), AI/ANs (4.47), and A/PIs (2.37) found in the West, and among NHWs (7.60) and NHBs (1.51) found in the Northeast.

Conclusions: Although TGCT incidence remained highest among NHWs between 2001 and 2016, the greatest increase was experienced by A/PI men.

Impact: Rising rates of TGCTs among men of all racial/ethnic backgrounds in the United States suggest that future attention is warranted.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269801PMC
June 2020

Analysis of aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross-sectional study (2016-2017).

Health Sci Rep 2020 Jun 6;3(2):e155. Epub 2020 May 6.

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland.

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 (AFB) exposure appears to be high. To examine whether AFB may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB-signature mutation in the gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the 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 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 mutation. The AFB-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 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes.

Conclusions: The presence of the R249S mutation in the samples studied suggests that AFB may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB and other risk factors for HCC in Guatemala is warranted.
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http://dx.doi.org/10.1002/hsr2.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202218PMC
June 2020

Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank.

Br J Cancer 2020 07 7;123(2):316-324. Epub 2020 May 7.

Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.

Background: Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC.

Methods: We harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases).

Results: Hysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors.

Conclusions: This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.
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http://dx.doi.org/10.1038/s41416-020-0835-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374167PMC
July 2020

Epidemiology of Hepatocellular Carcinoma.

Hepatology 2021 Jan 24;73 Suppl 1:4-13. Epub 2020 Nov 24.

Department of Medicine, Baylor College of Medicine, Houston, TX.

Liver cancer is a major contributor to the worldwide cancer burden. Incidence rates of this disease have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) accounts for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but their importance will likely decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral-associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcohol consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence of obesity and diabetes and controlling mycotoxin growth, are just as urgently required.
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http://dx.doi.org/10.1002/hep.31288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577946PMC
January 2021

Have incidence rates of liver cancer peaked in the United States?

Cancer 2020 07 15;126(13):3151-3155. Epub 2020 Apr 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

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.
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http://dx.doi.org/10.1002/cncr.32794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323860PMC
July 2020

Survival among patients with glioma in the US Military Health System: A comparison with patients in the Surveillance, Epidemiology, and End Results program.

Cancer 2020 07 14;126(13):3053-3060. Epub 2020 Apr 14.

Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, Maryland.

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.
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http://dx.doi.org/10.1002/cncr.32884DOI Listing
July 2020

One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study.

Int J Cancer 2020 10 25;147(8):2075-2090. Epub 2020 Apr 25.

Division of Cancer Epidemiology and Genetics, The National Cancer Institute, Bethesda, Maryland, USA.

Deficient intake of micronutrients involved in one-carbon metabolism (eg, choline, methionine, vitamin B 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 B (riboflavin), B (niacin), B and B . 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 B intake was associated with a lower HCC risk (HR = 0.60; 95% CI = 0.42-0.85; P = .008), and the association remained significant when all six micronutrients were examined simultaneously (HR = 0.32; 95% CI = 0.18-0.55; P < .0001). Among participants with >3 years of follow-up, higher total vitamin B intake was again associated with lower risk (HR = 0.37; 95% CI = 0.20-0.68; P = .001), whereas higher total vitamin B intake was associated with higher risk (HR = 2.04; 95% CI = 1.02-4.07; P = .04). Restricted cubic spline analyses showed a dose-response inverse association between total vitamin B intake and HCC risk, and dose-response positive association between total vitamin B intake and HCC risk. The study suggests that higher vitamin B intake is associated with lower HCC risk, whereas higher vitamin B intake is associated with increased risk.
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http://dx.doi.org/10.1002/ijc.33007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875463PMC
October 2020

Global Burden of 5 Major Types of Gastrointestinal Cancer.

Gastroenterology 2020 07 2;159(1):335-349.e15. Epub 2020 Apr 2.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Background & Aims: There were an estimated 4.8 million new cases of gastrointestinal (GI) cancers and 3.4 million related deaths, worldwide, in 2018. GI cancers account for 26% of the global cancer incidence and 35% of all cancer-related deaths. We investigated the global burden from the 5 major GI cancers, as well as geographic and temporal trends in cancer-specific incidence and mortality.

Methods: Data on primary cancers of the esophagus, stomach, colorectum, liver, and pancreas were extracted from the GLOBOCAN database for the year 2018, as well as from the Cancer Incidence in 5 Continents series, and the World Health Organization mortality database from 1960 onward. Age-standardized incidence and mortality rates were calculated by sex, country, and level of human development.

Results: We observed geographic and temporal variations in incidence and mortality for all 5 types of GI cancers. Esophageal, gastric, and liver cancers were more common in Asia than in other parts of the world, and the burden from colorectal and pancreatic cancers was highest in Europe and North America. There was a uniform decrease in gastric cancer incidence, but an increasing incidence of colorectal cancer in formerly low-incidence regions during the studied time period. We found slight increases in incidence of liver and pancreatic cancer in some high-income regions.

Conclusions: Although the incidence of some GI cancer types has decreased, this group of malignancies continues to pose major challenges to public health. Primary and secondary prevention measures are important for controlling these malignancies-most importantly reducing consumption of tobacco and alcohol, obesity control, immunizing populations against hepatitis B virus infection, and screening for colorectal cancer.
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http://dx.doi.org/10.1053/j.gastro.2020.02.068DOI Listing
July 2020

Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012.

Cancer 2020 06 4;126(11):2666-2678. Epub 2020 Mar 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

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.
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http://dx.doi.org/10.1002/cncr.32803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323858PMC
June 2020

The association between etiology of hepatocellular carcinoma and race-ethnicity in Florida.

Liver Int 2020 05 8;40(5):1201-1210. Epub 2020 Mar 8.

Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.

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.
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http://dx.doi.org/10.1111/liv.14409DOI Listing
May 2020

Comorbidity and stage at diagnosis among lung cancer patients in the US military health system.

Cancer Causes Control 2020 Mar 27;31(3):255-261. Epub 2020 Jan 27.

John P. Murtha Cancer Center Research Program, Uniformed Service University of the Health Sciences and Walter Reed National Military Medical Center, 6720A Rockledge Drive, Suite 310, Bethesda, MD, 20817, USA.

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.
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http://dx.doi.org/10.1007/s10552-020-01269-1DOI Listing
March 2020

High Dietary Intake of Vegetable or Polyunsaturated Fats Is Associated With Reduced Risk of Hepatocellular Carcinoma.

Clin Gastroenterol Hepatol 2020 11 9;18(12):2775-2783.e11. Epub 2020 Jan 9.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. Electronic address:

Background & Aims: We investigated associations of intake of total fats, specific dietary fats, and fats from different food sources with risk of hepatocellular carcinoma (HCC) using data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS).

Methods: We analyzed data from a total of 138,483 women and men who participated in the NHS or HPFS. A validated semi-quantitative food frequency questionnaire was sent to NHS participants in 1980, 1984, 1986, and every 4 years thereafter; dietary information was collected from participants in the HPFS in 1986 and every 4 years thereafter. Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression.

Results: After an average follow-up time of 26.6 years, 160 incident HCC cases were documented. Although there was a non-significant association between total fat intake and HCC, intake of vegetable fats reduced risk of HCC (HR for the highest vs lowest quartile, 0.61; 95% CI, 0.39-0.96; P = .02), but not animal or dairy fats. Replacing animal or dairy fats with an equivalent amount of vegetable fats was associated with a lower risk of HCC (HR per 1 standard deviation, 0.79; 95% CI, 0.65-0.97). Among fat subtypes, monounsaturated and polyunsaturated fatty acids, including n-3 (HR, 0.63; 95% CI, 0.41-0.96; P = .14) and n-6 polyunsaturated fatty acids (HR, 0.54; 95% CI, 0.34-0.86; P = .02), were inversely associated with risk of HCC. Higher ratios of monounsaturated or polyunsaturated fat to saturated fat were inversely associated with HCC risk (all P ≤ .02). In addition, when replacing saturated fats with monounsaturated or polyunsaturated fats, the HR per 1 standard deviation was 0.77 (95% CI, 0.64-0.92).

Conclusions: In an analysis of data from 2 large cohort studies, we found higher intake of vegetable fats and polyunsaturated fats to be associated with lower risk of HCC. Replacing animal or dairy fats with vegetable fats, or replacing saturated fats with monounsaturated or polyunsaturated fats, was associated with reduced risk of HCC.
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http://dx.doi.org/10.1016/j.cgh.2020.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343586PMC
November 2020

Age and Lymph Node Positivity in Patients With Colon and Rectal Cancer in the US Military Health System.

Dis Colon Rectum 2020 03;63(3):346-356

John P. Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, Maryland.

Background: Young age may be associated with an increased risk of lymph node involvement at diagnosis of colorectal cancer. Accessibility to care, which is related to cancer detection, tumor stage, and therefore lymph node positivity, may vary by age and thus influence research results.

Objective: The purpose of this study was to investigate whether young patients had an increased risk of lymph node-positive colon and rectal cancers in the Department of Defense Military Health System, which provides universal health care to its beneficiaries.

Design: This was a retrospective, cross-sectional study.

Settings: Patients were identified from the US Department of Defense Automated Central Tumor Registry.

Patients: Included patients were diagnosed with histologically confirmed primary stage I to III colon and rectal adenocarcinomas between 1989 and 2013, had surgery and ≥1 lymph node examined, and did not receive preoperative radiotherapy. Logistic regression was used to examine the relationships between age at diagnosis (18-49, 50-59, 60-69, and ≥70 y) and lymph node positivity overall and stratified by tumor T stage and number of lymph nodes examined.

Main Outcome Measures: Lymph node positivity of colon and rectal cancers was measured.

Results: The youngest patients (aged 18-49 y) were more likely to have lymph node-positive colon and rectal cancers compared with those who were aged ≥70 years after adjustment for potential confounders (OR = 2.04 and 95% CI, 1.63-2.56 for colon cancer; OR = 1.73 and 95% CI, 1.11-2.70 for rectal cancer). A similar tendency was shown in most colon and rectal cancer subgroups stratified by tumor T stage and number of lymph nodes examined.

Limitations: This study was limited by its small sample size for certain subgroup analyses. No information on comorbidities, BMI, or other indicators of health status was available.

Conclusions: In a universal healthcare system, young age was associated with increased lymph node positivity of colon and rectal cancers, suggesting that factors other than access to care may play a role in this association. See Video Abstract at http://links.lww.com/DCR/B90. EDAD Y POSITIVIDAD DE GANGLIOS LINFÁTICOS EN PACIENTES CON CÁNCER DEL COLON Y EL RECTO EN EL SISTEMA DE SALUD MILITAR DE EE UU: La edad temprana puede estar asociada con un mayor riesgo de compromiso de los ganglios linfáticos en el momento del diagnóstico de cáncer colorrectal. La accesibilidad a la atención medica, que está relacionada con la detección del cáncer, el estadio del tumor y, por lo tanto, la positividad de los ganglios linfáticos, puede variar según la edad y, por lo tanto, influir en los resultados de la investigación.Investigar si los pacientes jóvenes tenían un mayor riesgo de cáncer del colon y el recto con ganglios linfáticos positivos en el Sistema de Salud Militar del Departamento de Defensa, que brinda atención médica universal a sus beneficiarios.Estudio transversal retrospectivo.Se identificaron pacientes del Registro Automático Central de Tumores del Departamento de Defensa de los Estados Unidos.Fueron diagnosticados con adenocarcinomas del colon y el recto en estadio I-III confirmados histológicamente entre 1989-2013, se les realizó una cirugía y se examinaron ≥ 1 ganglio linfático, y no recibieron radioterapia preoperatoria. La regresión logística se utilizó para examinar las relaciones entre la edad al momento del diagnóstico (18-49, 50-59, 60-69 y ≥70 años) y la positividad de los ganglios linfáticos en general y fue estratificada por el estadio T tumoral y el número de ganglios linfáticos examinados.Positividad de ganglios linfáticos de cáncer del colon y el recto.Los pacientes más jóvenes (18-49 años) tenían más probabilidades de tener cáncer del colon y el recto con ganglios linfáticos positivos en comparación con aquellos que tenían 70 años o más después del ajuste por posibles factores de confusión (odds ratio: 2.04, intervalo de confianza del 95%: 1.63 -2.56 para el cáncer de colon; odds ratio: 1.73, intervalo de confianza del 95%: 1.11-2.70 para el cáncer de recto). Se mostró una tendencia similar en la mayoría de los subgrupos de cáncer del colon y el recto estratificados por el estadio T tumoral y el número de ganglios linfáticos examinados.Tamaño de muestra pequeño para ciertos análisis de subgrupos. No hay información sobre comorbilidades, índice de masa corporal u otros indicadores del estado de salud.En un sistema de salud universal, la edad joven se asoció con un aumento de la positividad de los ganglios linfáticos del cáncer del colon y el recto, lo que sugiere que otros factores además del acceso a la atención medica pueden desempeñar un papel en esta asociación. Consulte Video Resumen en http://links.lww.com/DCR/B90.
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http://dx.doi.org/10.1097/DCR.0000000000001555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021218PMC
March 2020