Publications by authors named "Samuel O Antwi"

31 Publications

Systemic anticoagulation is associated with decreased mortality and morbidity in acute pancreatitis.

Pancreatology 2021 Sep 8. Epub 2021 Sep 8.

Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA. Electronic address:

Background/objectives: Acute pancreatitis (AP) is a procoagulant state, and markers of coagulopathy are associated with AP severity. We aimed to explore the association of systemic anticoagulation therapy before AP onset with the inpatient outcomes of patients with acute pancreatitis.

Methods: This case-control, retrospective study used data from the Nationwide Inpatient Sample (Jan 2014-Dec 2016). We used medical coding data to identify patients with a principal diagnosis of AP who were receiving systemic anticoagulation therapy. Patients with anticoagulation were matched to those without it on the propensity for having anticoagulation. The propensity for having anticoagulation was estimated using a logistic regression model, matching for age, gender, race, median household income for patients' zip code, Charlson comorbidity score, region of hospital, location of hospital (urban/rural), teaching status of hospital, if admission day was on a weekend, pancreatic cancer class, obesity, tobacco usage. Secondary outcomes were inpatient outcomes and hospital expenditures.

Results: A total of 190,474 patients admitted for acute pancreatitis were identified, out of which 7827 patients were on anticoagulation. After propensity matching, 5776 matched pairs were successfully identified. Patients with AP on anticoagulation tended to have lower risk for ICU admission, acute kidney injury, organ failure or inpatient mortality. However, the group with anticoagulation had longer hospital length of stay and higher hospital costs.

Conclusions: Anticoagulation therapy may have a pivotal role in the pathogenesis and progression of AP. These data suggest a potential therapeutic role for anticoagulants in AP. Further studies are needed to better understand these observations.
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http://dx.doi.org/10.1016/j.pan.2021.09.003DOI Listing
September 2021

Cancer Mortality Rates Increasing vs Cardiovascular Disease Mortality Decreasing in the World: Future Implications.

Mayo Clin Proc Innov Qual Outcomes 2021 Jun 8;5(3):645-653. Epub 2021 Jun 8.

Neurologic Surgery Department, Mayo Clinic, Jacksonville, FL.

Objective: To highlight the current global trends in mortality for cardiovascular disease and cancer.

Methods: The World Health Organization and the World Bank DataBank databases were used to analyze mortality rates for cancer and cardiovascular disease by calculating age-standardized mortality rates (ASRs) from 2000 to 2015 for high-income, upper-middle-income, and lower-middle-income countries. Data for cancer mortality and population for 43 countries representing 5 of the 7 continents (except Australia and Antarctica) were analyzed.

Results: From 2000 to 2015, there was an increase in the ASR for cancer for both men and women irrespective of a country's income status, representing an overall 7% increase in cancer ASR (Pearson , +0.99; <.00001). We report a higher ASR for cancer in high-income countries than in upper-middle-income and lower-middle-income countries specifically; high-income countries saw a 3% increase in cancer ASR vs +31% for upper-middle-income and +19% for lower-middle-income countries (<.01). There has been a decrease in the ASR for cardiovascular disease for the 15 years analyzed (<.00001). In addition, high-income countries had a higher ASR for cardiovascular disease than upper-middle-income countries during the 15-year period (<.05).

Conclusion: We suspect that because of early detection and targeted interventions, cardiovascular disease mortality rates have decreased during the past decade. On the basis of our results, cancer mortality rates continue to rise, with the projection of surpassing cardiovascular disease mortality rates in the near future.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240359PMC
June 2021

Characteristics of Patients With Chronic Hepatitis B Virus Infection With Genotype E Predominance in Burkina Faso.

Hepatol Commun 2020 Dec 15;4(12):1781-1792. Epub 2020 Sep 15.

Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN.

Hepatitis B virus (HBV) genotype E (HBV-E) accounts for the majority of chronic hepatitis B (CHB) infections in West Africa. We aimed to determine factors associated with HBV-E-induced hepatocellular carcinoma (HCC) in West Africa. Data on patients from Burkina Faso who were hepatitis B surface antigen positive (HBsAg+) and had CHB were analyzed. HBV viral load and hepatitis B e antigen (HBeAg) status were measured in 3,885 individuals with CHB without HCC (CHB HCC-) and 59 individuals with CHB with HCC (CHB HCC+). HBV genotyping was performed for 364 subjects with CHB HCC- and 41 subjects with CHB HCC+. Overall, 2.5% of the CHB HCC- group was HBeAg+ compared with 0% of the CHB HCC+ group. Of the 364 patients who were CHB HCC- with available genotyping, the frequencies of HBV genotypes E and C/E were 70.3% and 12.9%, respectively. Age (odds ratio [OR] for older age, 1.08; 95% confidence interval [CI], 1.06-1.10 per 1-year increase in age), male sex (OR, 2.03; 95% CI, 1.11-3.69), and HBV viremia (OR, 1.48; 95% CI, 1.31-1.67 per 1 log10 IU/mL) were each associated with HCC diagnosis. Patients with genotype E had a lower HBeAg prevalence (6.3% vs. 14.9%), lower HBV viral load, and higher prevalence of cirrhosis (14.5% vs. 4.8%) than patients with genotype C/E. HBV-E is the most common circulating strain (70.3%) in West African patients. HCC was associated with older age, male sex, and high HBV viral load. It is expected that these results will further inform guidance on clinical management of HBV infection in West Africa.
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http://dx.doi.org/10.1002/hep4.1595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706297PMC
December 2020

Shorter Treatment-Naïve Leukocyte Telomere Length is Associated with Poorer Overall Survival of Patients with Pancreatic Ductal Adenocarcinoma.

Cancer Epidemiol Biomarkers Prev 2021 01 13;30(1):210-216. Epub 2020 Nov 13.

Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.

Background: Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.

Methods: The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models.

Results: Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HR = 1.13, 95% CI: 1.01-1.28, = 0.03; HR = 1.29, 95% CI: 1.05-1.59, = 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HR = 0.91; 95% CI: 0.73-1.12), locally advanced tumors (HR = 1.29; 95% CI: 1.07-1.56), and metastatic tumors (HR = 1.17; 95% CI: 0.96-1.42), = 0.04.

Conclusion: Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC.

Impact: Peripheral blood LTL might be a prognostic marker for PDAC.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855627PMC
January 2021

Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2020 12 23;29(12):2735-2739. Epub 2020 Sep 23.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome.

Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data.

Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex.

Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk.

Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710600PMC
December 2020

Reply to: Comments on "One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study".

Authors:
Samuel O Antwi

Int J Cancer 2021 01 16;148(1):254. Epub 2020 Jul 16.

Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Jacksonville, Florida, USA.

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http://dx.doi.org/10.1002/ijc.33186DOI Listing
January 2021

Leukocyte Telomere Length and Its Interaction with Germline Variation in Telomere-Related Genes in Relation to Pancreatic Adenocarcinoma Risk.

Cancer Epidemiol Biomarkers Prev 2020 07 20;29(7):1492-1500. Epub 2020 Apr 20.

Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.

Background: Leukocyte telomere length (LTL) has been associated with risk of multiple cancers, but its association with pancreatic ductal adenocarcinoma (PDAC) is unclear. We therefore investigated the association between peripheral blood LTL and PDAC risk, and examined effect modification by candidate SNPs previously reported to be associated with variation in LTL.

Methods: A case-control study of 1,460 PDAC cases and 1,459 frequency-matched controls was performed using biospecimens and data from the Mayo Clinic Biospecimen Resource for Pancreas Research. Quantitative PCR was used to measure LTL and categorized into tertiles based on sex-specific control distribution. Eleven telomere-related SNPs also were genotyped. Logistic regression was used to calculate ORs and 95% confidence intervals (CI).

Results: Shorter peripheral blood LTL was associated with a higher risk of PDAC (OR = 1.26, 95% CI = 1.03-1.54, = 0.02; OR = 1.14, 95% CI = 1.02-1.28), but the association was restricted to cases with treatment-naïve blood samples (OR = 1.51, 95% CI = 1.16-1.96, = 0.002; OR = 1.25, 95% CI = 1.08-1.45) and not cases whose blood samples were collected after initiation of cancer therapy (OR = 1.10, 95% CI = 0.87-1.39, = 0.42; OR = 1.08, 95% CI = 0.94-1.23). Three SNPs (-rs10936599, rs11125529, and rs1317082) were each associated with interindividual variation in LTL among controls, but there was no evidence of effect modification by these SNPs.

Conclusions: Treatment-naïve short LTL is associated with a higher risk of PDAC, and the association does not differ by germline variation in the candidate telomere-related SNPs examined.

Impact: Peripheral blood LTL might serve as a molecular marker for risk modeling to identify persons at high risk of PDAC.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334088PMC
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

Independent and Joint Use of Statins and Metformin by Elderly Patients With Diabetes and Overall Survival Following HCC Diagnosis.

J Clin Gastroenterol 2020 May/Jun;54(5):468-476

Transplant Hepatology, Mayo Clinic, Jacksonville, FL.

Goal: To investigate associations of prediagnosis and postdiagnosis use of statins and metformin on overall survival of patients with diabetes who later developed HCC.

Background: Statins and metformin have received considerable interest as potential chemopreventive agents against hepatocellular carcinoma (HCC) development in individuals with type 2 diabetes mellitus (T2DM); however, their impact on overall survival of patients with T2DM who later develop HCC (diabetic HCC patients) is unclear.

Study: Data on 2499 elderly diabetic HCC patients obtained from the SEER-Medicare program (2009 to 2013) were analyzed. Patients were categorized based on use of statins only, metformin only, both, or neither (reference for all comparisons). The patients were further categorized based on: (1) metformin dose: ≤1500 or >1500 mg/d; (2) statins functional form: hydrophilic (pravastatin and rosuvastatin) or lipophilic (atorvastatin, fluvastatin, lovastatin, and simvastatin); (3) statins potency: high (atorvastatin, rosuvastatin, and simvastatin) or low (fluvastatin, lovastatin, and pravastatin); and (4) individual statins type. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models.

Results: Prediagnosis use of metformin dose ≤1500 mg/d was associated with lower risk of death after HCC diagnosis in patients with T2DM (HR, 0.72; 95% CI, 0.58-0.91), adjusting for postdiagnosis metformin dose, diabetes severity, Charlson comorbidity index, tumor characteristics, and other relevant factors. No association was found for prediagnosis metformin dose >1500 mg/d or postdiagnosis metformin use. Further, no association was found for either prediagnosis or postdiagnosis statins use.

Conclusions: Prediagnosis use of metformin dose ≤1500 mg/d is associated with longer overall survival of elderly diabetic HCC patients.
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http://dx.doi.org/10.1097/MCG.0000000000001182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150664PMC
June 2021

Increasing mortality of intrahepatic cholangiocarcinoma in the US: are gender-specific risk factors important?

Hepatobiliary Surg Nutr 2019 Dec;8(6):635-636

Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA.

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http://dx.doi.org/10.21037/hbsn.2019.10.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943003PMC
December 2019

Genome-wide discovery and validation of diagnostic DNA methylation-based biomarkers for hepatocellular cancer detection in circulating cell free DNA.

Theranostics 2019 25;9(24):7239-7250. Epub 2019 Sep 25.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is growing in incidence but treatment options remain limited, particularly for late stage disease. As liver cirrhosis is the principal risk state for HCC development, markers to detect early HCC within this patient population are urgently needed. Perturbation of epigenetic marks, such as DNA methylation (5mC), is a hallmark of human cancers, including HCC. Identification of regions with consistently altered 5mC levels in circulating cell free DNA (cfDNA) during progression from cirrhosis to HCC could therefore serve as markers for development of minimally-invasive screens of early HCC diagnosis and surveillance. : To discover DNA methylation derived biomarkers of HCC in the background of liver cirrhosis, we profiled genome-wide 5mC landscapes in patient cfDNA using the Infinium HumanMethylation450k BeadChip Array. We further linked these findings to primary tissue data available from TCGA and other public sources. Using biological and statistical frameworks, we selected CpGs that robustly differentiated cirrhosis from HCC in primary tissue and cfDNA followed by validation in an additional independent cohort. : We identified CpGs that segregate patients with cirrhosis, from patients with HCC within a cirrhotic liver background, through genome-wide analysis of cfDNA 5mC landscapes. Lasso regression analysis pinpointed a panel of probes in our discovery cohort that were validated in two independent datasets. A panel of five CpGs (cg04645914, cg06215569, cg23663760, cg13781744, and cg07610777) yielded area under the receiver operating characteristic (AUROC) curves of 0.9525, 0.9714, and 0.9528 in cfDNA discovery and tissue validation cohorts 1 and 2, respectively. Validation of a 5-marker panel created from combining hypermethylated and hypomethylated CpGs in an independent cfDNA set by bisulfite pyrosequencing yielded an AUROC of 0.956, compared to the discovery AUROC of 0.996. : Our finding that 5mC markers derived from primary tissue did not perform well in cfDNA, compared to those identified directly from cfDNA, reveals potential advantages of starting with cfDNA to discover high performing markers for liquid biopsy development.
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http://dx.doi.org/10.7150/thno.35573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831291PMC
September 2020

Risk of Hepatocellular Carcinoma Following Use of Direct Acting Antiviral Medications for Treatment of Chronic Hepatitis C.

Cancer Prev Res (Phila) 2019 12 26;12(12):891-902. Epub 2019 Aug 26.

Department of Transplantation, Mayo Clinic, Jacksonville, Florida.

Direct-acting antivirals (DAA) are now the mainstay of treatment for patients with chronic hepatitis C virus (HCV); however, there is some controversy over whether use of DAAs for HCV, as compared with IFN-based regimens, leads to an increased risk for hepatocellular carcinoma (HCC) development. We investigated the association between use of DAAs and subsequent development of HCC in longitudinal data from patients with HCV from diverse backgrounds (various ages, ethnicities, and geographic regions) across the United States. The design was a retrospective study performed using medical and pharmacy claims from OptumLabs. HCV treatment exposure was categorized as DAA-only, DAA + IFN, any-DAA, or IFN-only. To account for confounding by indication, inverse probability of treatment weighting was performed. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). We identified 5,781 patients with HCV with no history of HCC at baseline. Compared with IFN-only regimen, no significant increase in HCC risk was found for use of DAA-only (HR, 1.53; 95% CI, 0.73-3.23), DAA + IFN (HR, 1.02; 95% CI, 0.51-2.06), or any-DAA (HR, 1.04; 95% CI, 0.65-1.65). When stratified by sustained virological response (SVR), we noted a higher HCC risk for DAA-only among patients who achieved SVR post-treatment (HR, 7.53; 95% CI, 1.48-38.34), but the CIs were wide, which might be due to the small sample size of the subgroups. Among those who did not achieve SVR, no association was found for use of DAA-only (HR, 0.59; 95% CI, 0.19-1.91). These findings do not provide compelling evidence for the conception that use of DAAs for HCV is associated with increased risk of HCC development.
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http://dx.doi.org/10.1158/1940-6207.CAPR-19-0162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893130PMC
December 2019

A SEER-based multi-ethnic picture of advanced intrahepatic cholangiocarcinoma in the United States pre- and post-the advent of gemcitabine/cisplatin.

J Gastrointest Oncol 2018 Dec;9(6):1063-1073

Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ, USA.

Background: Cholangiocarcinoma (CCA) is a rare, lethal cancer with 5-year survival of less than 10%. Although incidence rates have been increasing in the United States, ethnic variations in survival have not been investigated. We examined multi-ethnic variation in overall survival (OS) and CCA-specific survival (CSS) using data from the population-based Surveillance Epidemiology and End Results (SEER) program in the 4-year period after introduction of gemcitabine/cisplatin (GC) as treatment for CCA, compared with prior years.

Methods: The study included data from 5,616 advanced, intrahepatic CCA cases reported in SEER between 1990 and 2013. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated to examine OS and CSS by ethnicity, age, gender and in the pre- and post-GC era (1990-2000, 2001-2009 2010-2013).

Results: Compared to non-Hispanic Whites, Hispanics had poorer 3-year OS (HR 1.11, 95% CI: 1.03-1.20) and 3-year CSS (HR 1.15, 95% CI: 1.05-1.25). Similarly, non-Hispanic Blacks had 3-year OS (HR 1.21, 95% CI: 1.10-1.34) and 3-year CSS (HR 1.21, 95% CI: 1.09-1.35). Males and older patients had shorter survival compared to females and younger patients. OS and CSS were both improved for patients' post-advent of GC. Statistically significant improvement in CSS pre- and post-advent of GC was noted in non-Hispanic Whites, while Hispanics actually had worsened survival.

Conclusions: Hispanics and non-Hispanic Blacks have worse survival after diagnosis with advanced, intrahepatic CCA. Further studies are needed to determine determinants of poor survival among these groups.
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http://dx.doi.org/10.21037/jgo.2018.07.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286951PMC
December 2018

Response to Loco-Regional Therapy Predicts Outcomes After Liver Transplantation for Combined Hepatocellular-Cholangiocarcinoma.

Ann Hepatol 2018 Oct;17(6):969-979

Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA.

Introduction And Aim: Combined hepatocellular-cholangiocarcinoma (HCC-CCA) is a rare liver malignancy distinct from either hepatocellular carcinoma (HCC) or cholangiocarcinoma. Liver transplantation (LT) is not recommended for HCC-CCA because of suboptimal outcomes. Non-invasive diagnosis of HCC-CCA is extremely challenging; thus, some HCC-CCAs are presumed as HCC on imaging and listed for LT with the correct diagnosis ultimately made on explant pathology. We compared HCC-CCA with HCC to determine the utility of response to pre-transplant loco-regional therapy (LRT) in predicting outcomes for HCC-CCA after LT as a potential means of identifying appropriate HCC-CCA patients for LT.

Material And Methods: Retrospective review of 19 patients with pathologically confirmed HCC-CCA were individually matched to 38 HCC patients (1:2) based on age, sex, and Milan criteria at listing was performed. The modified response evaluation criteria in solid tumors was used to categorize patients as responders or non-responders to pre-transplant LRT based on imaging performed before and after LRT. Overall survival (OS) and recurrence-free survival (RFS) were examined.

Results: OS at 3 years post-transplant was 74% for HCC-CCA and 87% for HCC. RFS at 3 years was 74% for HCC-CCA, and 87% for HCC. Among responders to LRT, the 3-year OS was 92% for HCC-CCA and 88% for HCC; among non-responders, 3-year OS was 43% for HCC-CCA and 83% for HCC. Higher 3-year OS was observed among HCC-CCA responders (77%) compared with HCC-CCA non-responders (23%).

Conclusions: OS was similarly high among.
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http://dx.doi.org/10.5604/01.3001.0012.7197DOI Listing
October 2018

Germline Rare Coding Variants and Risk of Pancreatic Cancer in Minority Populations.

Cancer Epidemiol Biomarkers Prev 2018 11 23;27(11):1364-1370. Epub 2018 Jul 23.

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Pathogenic germline mutations in the tumor suppressor gene are rare and associated with highly penetrant familial melanoma and pancreatic cancer in non-Hispanic whites (NHW). To date, the prevalence and impact of rare coding variants (RCV) in racial minority groups remain poorly characterized. We examined the role of RCVs on the risk of pancreatic cancer among minority subjects. We sequenced in 220 African American (AA) pancreatic cancer cases, 900 noncancer AA controls, and 183 Nigerian controls. RCV frequencies were determined for each group and compared with that of 1,537 NHW patients with pancreatic cancer. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for both a case-case comparison of RCV frequencies in AAs versus NHWs, and case-control comparison between AA cases versus noncancer AA controls plus Nigerian controls. Smaller sets of Hispanic and Native American cases and controls also were sequenced. One novel missense RCV and one novel frameshift RCV were found among AA patients: 400G>A and 258_278del. RCV carrier status was associated with increased risk of pancreatic cancer among AA cases (11/220; OR, 3.3; 95% CI, 1.5-7.1; = 0.004) compared with AA and Nigerian controls (17/1,083). Further, AA cases had higher frequency of RCVs: 5.0% (OR, 13.4; 95% CI, 4.9-36.7; < 0.001) compared with NHW cases (0.4%). RCVs are more common in AA than in NHW patients with pancreatic cancer and associated with moderately increased pancreatic cancer risk among AAs. RCVs in are frequent in AAs and are associated with risk for pancreatic cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-17-1065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214745PMC
November 2018

Risk of Different Cancers Among First-degree Relatives of Pancreatic Cancer Patients: Influence of Probands' Susceptibility Gene Mutation Status.

J Natl Cancer Inst 2019 03;111(3):264-271

Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

Background: Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands.

Methods: Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided.

Results: Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95% CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95% CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95% CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95% CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95% CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95% CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95% CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95% CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands.

Conclusions: Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers.
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http://dx.doi.org/10.1093/jnci/djx272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410948PMC
March 2019

Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.

JAMA 2018 06;319(23):2401-2409

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Importance: Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined.

Objective: To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer.

Design, Setting, And Participants: Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123 136 individuals with exome sequence data in the public Genome Aggregation Database and 53 105 in the Exome Aggregation Consortium database.

Exposures: Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer.

Main Outcomes And Measures: Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls.

Results: Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).

Conclusions And Relevance: In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.
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http://dx.doi.org/10.1001/jama.2018.6228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092184PMC
June 2018

Racial, Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014.

Ann Hepatol 2018 July - August ,;17(4):604-614

Department of Transplantation Mayo Clinic, Jacksonville, Florida, United States.

Introduction And Aim: Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014).

Material And Methods: We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality.

Results: Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year allcause mortality (HR = 1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, and Blacks and American Indians/Alaska Natives.

Conclusion: The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.
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http://dx.doi.org/10.5604/01.3001.0012.0929DOI Listing
April 2019

Pancreatic cancer risk is modulated by inflammatory potential of diet and ABO genotype: a consortia-based evaluation and replication study.

Carcinogenesis 2018 07;39(8):1056-1067

Department of Population Health, New York University School of Medicine, New York, NY, USA.

Diets with high inflammatory potential are suspected to increase risk for pancreatic cancer (PC). Using pooled analyses, we examined whether this association applies to populations from different geographic regions and population subgroups with varying risks for PC, including variation in ABO blood type. Data from six case-control studies (cases, n = 2414; controls, n = 4528) in the Pancreatic Cancer Case-Control Consortium (PanC4) were analyzed, followed by replication in five nested case-control studies (cases, n = 1268; controls, n = 4215) from the Pancreatic Cancer Cohort Consortium (PanScan). Two polymorphisms in the ABO locus (rs505922 and rs8176746) were used to infer participants' blood types. Dietary questionnaire-derived nutrient/food intake was used to compute energy-adjusted dietary inflammatory index (E-DII®) scores to assess inflammatory potential of diet. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression. Higher E-DII scores, reflecting greater inflammatory potential of diet, were associated with increased PC risk in PanC4 [ORQ5 versus Q1=2.20, 95% confidence interval (CI) = 1.85-2.61, Ptrend < 0.0001; ORcontinuous = 1.20, 95% CI = 1.17-1.24], and PanScan (ORQ5 versus Q1 = 1.23, 95% CI = 0.92-1.66, Ptrend = 0.008; ORcontinuous = 1.09, 95% CI = 1.02-1.15). As expected, genotype-derived non-O blood type was associated with increased PC risk in both the PanC4 and PanScan studies. Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction = 0.10 in PanC4 and Pinteraction=0.13 in PanScan). The results show that consuming a pro-inflammatory diet and carrying non-O blood type are each individually, but not interactively, associated with increased PC risk.
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http://dx.doi.org/10.1093/carcin/bgy072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067129PMC
July 2018

Racial, Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic Cholangiocarcinoma in the United States; 1995-2014.

Ann Hepatol 2018 Mar;17(2):274-285

Department of Transplantation Mayo Clinic, Jacksonville, Florida, United States.

Introduction: Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014).

Materials And Methods: We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality.

Results: Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year all-cause mortality (HR=1.11, 95%CI: 1.05-1.19) and poorer iCCA-specific mortality (HR=1.15, 95%CI: 1.07-1.24). Survival rates were poor also for individuals age 45 years or older, men, Blacks, and American Indians/Alaska Natives.

Conclusion: The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.
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http://dx.doi.org/10.5604/01.3001.0010.8663DOI Listing
March 2018

Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review.

Pancreas 2018 03;47(3):265-271

Many risk factors have been firmly established for pancreatic cancer (PC), but the molecular processes by which known risk factors influence susceptibility to PC are not clear. There has been a recent upsurge of interest in the role of telomere length (TL), the protective DNA sequence repeats at chromosome ends, in pancreatic carcinogenesis. Given this heightened interest, we performed an in-depth, focused, and up-to-date review of the epidemiological evidence linking leukocyte TL (LTL) with PC risk. We searched MEDLINE, Embase, and the Cochrane Library databases for all published studies on LTL and PC risk, up to May 2017. Five studies were identified for review: 4 nested case-control studies and 1 retrospective case-control study. Two studies found opposite associations between LTL and PC risk: 1 found a dose-response positive association and the other found a dose-response inverse association. Two studies also found a "U-shaped" association, whereas another reported a weak nonlinear relationship. We offer potential reasons for the conflicting findings including variation in study design, biospecimen characteristics, and differences in interlaboratory measurements of TL. Future studies should carefully control for risk factors of PC that are associated also with telomere attrition and investigate the role of genetic variation in TL maintenance.
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http://dx.doi.org/10.1097/MPA.0000000000000995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808594PMC
March 2018

Inflammatory potential of diet and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Int J Cancer 2018 06 2;142(12):2461-2470. Epub 2018 Feb 2.

Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC.

Inflammation plays a central role in pancreatic cancer etiology and can be modulated by diet. We aimed to examine the association between the inflammatory potential of diet, assessed with the Dietary Inflammatory Index (DII®), and pancreatic cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial prospective cohort. Our study included 101,449 participants aged 52-78 years at baseline who completed both baseline questionnaire and a diet history questionnaire. Energy-adjusted DII (E-DII) scores were computed based on food and supplement intake. Cox proportional hazards models and time dependent Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with participants in the lowest E-DII quintile (most anti-inflammatory scores) as referent. After a median 8.5 years of follow-up, 328 pancreatic cancer cases were identified. E-DII scores were not associated with pancreatic cancer risk in the multivariable model (HR  = 0.94; 95% CI = 0.66-1.35; p-trend = 0.43). Time significantly modified the association (p-interaction = 0.01). During follow up <4 years, there was suggestive evidence of an inverse association between E-DII and pancreatic cancer (HR  = 0.60; 95% CI = 0.35-1.02; p-trend = 0.20) while there was a significant positive trend in the follow up ≥4 years (HR  = 1.31; 95% CI = 0.83-2.08; p-trend = 0.03). Similar results were observed for E-DII from food only. Our study does not support an association between inflammatory potential of diet and pancreatic cancer risk; however, heterogeneous results were obtained with different follow-up times. These divergent associations may result from the influences of undetected disease in the short-term.
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http://dx.doi.org/10.1002/ijc.31271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908732PMC
June 2018

Alcohol consumption, variability in alcohol dehydrogenase genes and risk of renal cell carcinoma.

Int J Cancer 2018 02 28;142(4):747-756. Epub 2017 Oct 28.

Department of Health Sciences Research, 4500 San Pablo Road, Jacksonville, FL.

Alcohol consumption has been associated inversely with renal cell carcinoma (RCC) risk; however, no study has examined effect modification by germline variation in alcohol-metabolizing genes. We investigated whether the association between alcohol intake and RCC risk is modulated by germline variants in alcohol dehydrogenase genes in a large case-control study. Data from 652 RCC cases and 1,366 non-cancer controls were analyzed. Alcohol intake was assessed using a standardized risk factor questionnaire. Three previously genotyped polymorphisms in ADH6 and ADH7 with the TaqMan assay were examined. Odds ratios (ORs) and 95% confidence interval (CI) were calculated using logistic regression, adjusting for covariates. Compared to non-drinkers, ever consumption of alcohol was associated with lower RCC risk (OR = 0.52, 95% CI = 0.42-0.65). Analysis with cubic spline regression curve showed a "J-shaped" relationship between alcohol drinks/day and RCC risk, such that there was no added benefit against RCC for consumption of more than two drinks/day. We observed effect modification by variation in rs1154454 (ADH7) (p  = 0.007); a per unit increase in alcohol drink/day was associated with 35% lower RCC risk among non-minor allele carriers, a 27% lower risk among those who carry one copy of the minor allele, but no association was observed among those with two copies of the minor allele. These findings indicate that alcohol consumption is associated with lower RCC risk. Consuming more than two drinks a day does not confer additional protection against RCC. The association between alcohol intake and RCC risk appears to be modulated by inter-individual germline variation in alcohol-metabolizing genes.
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http://dx.doi.org/10.1002/ijc.31103DOI Listing
February 2018

Coffee consumption and risk of renal cell carcinoma.

Cancer Causes Control 2017 Aug 24;28(8):857-866. Epub 2017 Jun 24.

Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.

Background: Studies have suggested an inverse association between coffee consumption and risk of renal cell carcinoma (RCC); however, data regarding decaffeinated coffee are limited.

Methods: We conducted a case-control study of 669 incident RCC cases and 1,001 frequency-matched controls. Participants completed identical risk factor questionnaires that solicited information about usual coffee consumption habits. The study participants were categorized as non-coffee, caffeinated coffee, decaffeinated coffee, or both caffeinated and decaffeinated coffee drinkers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for multiple risk factors for RCC.

Results: Compared with no coffee consumption, we found an inverse association between caffeinated coffee consumption and RCC risk (OR 0.74; 95% CI 0.57-0.99), whereas we observed a trend toward increased risk of RCC for consumption of decaffeinated coffee (OR 1.47; 95% CI 0.98-2.19). Decaffeinated coffee consumption was associated also with increased risk of the clear cell RCC (ccRCC) subtype, particularly the aggressive form of ccRCC (OR 1.80; 95% CI 1.01-3.22).

Conclusions: Consumption of caffeinated coffee is associated with reduced risk of RCC, while decaffeinated coffee consumption is associated with an increase in risk of aggressive ccRCC. Further inquiry is warranted in large prospective studies and should include assessment of dose-response associations.
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http://dx.doi.org/10.1007/s10552-017-0913-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782814PMC
August 2017

Telomere Length and Pancreatic Cancer Risk-Reply.

Cancer Epidemiol Biomarkers Prev 2017 07 20;26(7):1158-1159. Epub 2017 Jun 20.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1158/1055-9965.EPI-17-0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604857PMC
July 2017

Genetically Predicted Telomere Length is not Associated with Pancreatic Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2017 06 6;26(6):971-974. Epub 2017 Mar 6.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Epidemiologic associations of leukocyte telomere length (LTL) and pancreatic ductal adenocarcinoma (PDAC) have been inconsistent owing, in part, to variation in telomere length (TL) assessment across studies. To overcome this limitation and address concerns of potential reverse causation, we used carriage of telomere-related alleles to genetically predict TL and examined its association with PDAC. A case-control study of 1,500 PDAC cases and 1,500 controls, frequency-matched on age and sex was performed. Eight of nine polymorphisms previously associated with variation in LTL were analyzed. Genetic risk scores (GRS) consisting of the TL-related polymorphisms were computed as the number of long TL alleles carried by an individual scaled to published kilobase pairs of TL associated with each allele. Participants were further categorized on the basis of the number of short TL alleles they carry across all eight SNPs. Associations were examined in additive and dominant models using logistic regression to calculate ORs and 95% confidence intervals (CI). In age- and sex-adjusted models, one short TL allele (rs10936599, T) was associated with reduced risk, whereas another short TL allele (rs2736100, A) was associated with increased risk, with per-allele ORs of 0.89 (95% CI, 0.79-0.99) and 1.13 (95% CI, 1.01-1.24), respectively. No association was observed with GRS or short TL allele counts, and no associations were observed in the dominant models. Findings suggest that genetically predicted short TL is not associated with PDAC risk. Common genetic determinants of short TL do not appear to influence PDAC risk. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483972PMC
June 2017

Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP).

Prostate 2016 09 8;76(12):1053-66. Epub 2016 Jun 8.

David Geffen School of Medicine at UCLA, Los Angeles, California.

Background: Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness.

Methods: Data on African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP.

Results: Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β-cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34-0.89, Ptrend  = 0.02), while an inverse association was observed between dietary β-cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36-0.87, Ptrend  = 0.01). Adipose tissue α-carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α-carotene (Ptrend  = 0.07) and lycopene (Ptrend  = 0.11), and CaP aggressiveness among EAs only.

Conclusions: These results suggest that diets high in lycopene and β-cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations. Prostate 76:1053-1066, 2016. © 2016 Wiley Periodicals, Inc.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080909PMC
http://dx.doi.org/10.1002/pros.23189DOI Listing
September 2016

Pancreatic cancer: associations of inflammatory potential of diet, cigarette smoking and long-standing diabetes.

Carcinogenesis 2016 05 12;37(5):481-90. Epub 2016 Feb 12.

Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.

Epidemiologic studies show strong associations between pancreatic cancer (PC) and inflammatory stimuli or conditions such as cigarette smoking and diabetes, suggesting that inflammation may play a key role in PC. Studies of dietary patterns and cancer outcomes also suggest that diet might influence an individual's risk of PC by modulating inflammation. We therefore examined independent and joint associations between inflammatory potential of diet, cigarette smoking and long-standing (≥5 years) type II diabetes in relation to risk of PC. Analyses included data from 817 cases and 1756 controls. Inflammatory potential of diet was measured using the dietary inflammatory index (DII), calculated from dietary intake assessed via a 144-item food frequency questionnaire, and adjusted for energy intake. Information on smoking and diabetes were obtained via risk factor questionnaires. Associations were examined using multivariable-adjusted logistic regression. Higher DII scores, reflecting a more proinflammatory diet, were associated with increased risk of PC [odds ratio (OR)Quintile 5 versus 1 = 2.54, 95% confidence interval (CI) = 1.87-3.46, P trend < 0.0001]. Excess risk of PC also was observed among former (OR = 1.29, 95% CI = 1.07-1.54) and current (OR = 3.40, 95% CI = 2.28-5.07) smokers compared with never smokers, and among participants with long-standing diabetes (OR = 3.09, 95% CI = 2.02-4.72) compared with nondiabetics. Joint associations were observed for the combined effects of having greater than median DII score, and being a current smoker (OR = 4.79, 95% CI = 3.00-7.65) or having long-standing diabetes (OR = 6.03, 95% CI = 3.41-10.85). These findings suggest that a proinflammatory diet may act as cofactor with cigarette smoking and diabetes to increase risk of PC beyond the risk of any of these factors alone.
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http://dx.doi.org/10.1093/carcin/bgw022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843052PMC
May 2016

Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer.

Cancer Causes Control 2015 Nov 21;26(11):1583-91. Epub 2015 Aug 21.

Division of Epidemiology, Health Sciences Research, Mayo Clinic, 200 First Street SW, Charlton 6-243, Rochester, MN, 55905, USA.

Purpose: Exposure to various chemicals and heavy metals has been associated with risk of different cancers; however, data on whether such exposures may increase the risk of pancreatic cancer (PC) are very limited and inconclusive. We examined PC risk with self-reported exposures to chemicals and heavy metals.

Methods: The design was a clinic-based, case-control study of data collected from 2000 to 2014 at Mayo Clinic in Rochester, Minnesota, USA. Cases were rapidly ascertained patients diagnosed with pancreatic ductal adenocarcinoma (n = 2,092). Controls were cancer-free patients in primary care clinics (n = 2,353), frequency-matched to cases on age, race, sex, and state/region of residence. Cases and controls completed identical risk factor questionnaires, which included yes/no questions about regular exposure to pesticides, asbestos, benzene, chlorinated hydrocarbons, chromium, and nickel. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) comparing those who affirmed exposure to each of the chemicals/heavy metals to those who reported no regular exposure, adjusting for potential confounders.

Results: Self-reported regular exposure to pesticides was associated with increased odds of PC (OR 1.21, 95% CI 1.02-1.44). Regular exposure to asbestos (OR 1.54, 95% CI 1.23-1.92), benzene (OR 1.70, 95% CI 1.23-2.35), and chlorinated hydrocarbons (OR 1.63, 95% CI 1.32-2.02) also was associated with higher odds of PC. Chromium and nickel exposures were not significantly associated with PC.

Conclusions: These findings add to the limited data suggesting that exposure to pesticides, asbestos, benzene, and chlorinated hydrocarbons may increase PC risk. They further support the importance of implementing strategies that reduce exposure to these substances.
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http://dx.doi.org/10.1007/s10552-015-0652-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624268PMC
November 2015

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer.

Cancer Epidemiol 2015 Oct 9;39(5):752-62. Epub 2015 Jul 9.

Epidemiology and Biostatistics Arnold School of Public Health, 915 Greene St, Columbia, SC 29208, United States; Cancer Prevention and Control Program, Arnold School of Public Health, 915 Greene St, Columbia, SC 29208, United States.

Background: Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA.

Methods: Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates.

Results: After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only.

Conclusions: Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence.
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http://dx.doi.org/10.1016/j.canep.2015.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577465PMC
October 2015
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