Epidemiologic Research Program Research Articles

An Update on Gastrointestinal Parasitic Infection in Captive Wild Animals in Bangladesh.

Gastrointestinal parasites cause health problems and even death in captive animals. These animals are more susceptible to parasitic infestations because of confinement and stress. The aim of the study is to describe parasitic causal agents in captive wild animals at the Bangladesh National Zoo, Chittagong Zoo, and Tilagarh Eco Park, in Sylhet. A total of 54 fecal samples were collected from the Bangladesh Zoo, Chittagong Zoo, and Tilagarh Eco Park from April 2022 to November 2022. Samples were collected from animals of the groups Aves (16), Reptiles (4), Artiodactyla (23), Perissodactyla (8), and Proboscidea (3). All samples were examined using a modified formalin ether sedimentation technique. Fecal examination consoled an overall occurrence of 61.1%. Out of 54 samples, 33 were positive for parasitic infection. The parasites observed were as follows: Ascarididae eggs (57.58%), Capillaria spp. (18.18%), Strongyloides spp. (9.09%), Trichuris spp. (6.06%), and mixed infection (9.09%). The order Reptiles had a 100% infection rate, while Aves had the lowest infection rate (50%). Only nematodes were detected in this study. Without showing evident, clinical signs and symptoms of disease, the prevalence of gastrointestinal parasites is high. This indicates a subclinical infection. This study shows that more epidemiological research and sanitation management programs, including regular antihelminthic therapy for controlling parasitic infection, should be adopted in zoos and ecoparks.

Underdiagnosis and misclassification of COPD in Sweden – A Nordic Epilung study

IntroductionThe prevalence of COPD tends to level off in populations with decreasing prevalence of smoking but the extent of underdiagnosis in such populations needs further investigation. AimTo investigate underdiagnosis and misclassification of COPD with a focus on socio-economy, lifestyle determinants and healthcare utilization. MethodThe 1839 participants were selected from two ongoing large-scale epidemiological research programs: The Obstructive Lung Disease in Northern Sweden Studies and the West Sweden Asthma Study. COPDGOLD was defined according to the fixed post-bronchodilator spirometric criteria FEV1/FVC<0.70 in combination with respiratory symptoms. ResultsAmong the 128 participants who fulfilled the criteria for COPDGOLD, the underdiagnosis was 83.6% (n = 107) of which 57.9% were men. The undiagnosed participants were younger, had higher FEV1% of predicted and less frequently a family history of bronchitis. One in four of the undiagnosed had utilized healthcare and had more frequently utilized healthcare due to a burden of respiratory symptoms than the general population without COPD. Underdiagnosis was not related to educational level. Misclassification of COPD was characterized by being a woman with low education, ever smoker, having respiratory symptoms and having a previous asthma diagnosis. ConclusionIn the high income country Sweden, the underdiagnosis of COPD was highly prevalent.Reduced underdiagnosis can contribute to risk factor modification, medical treatment and self-management strategies in early stages of the disease, which may prevent disease progression and improve the quality of life among those affected. Therefore, there is a need to increase the use of spirometry in primary care to improve the diagnostic accuracy.

Research Publications from the ATS MECOR Program in Turkiye.

The American Thoracic Society (ATS) Methods in Epidemiologic, Clinical, and Operations Research (MECOR) Program aims to build research capacity in low and middle-income countries. MECOR has three levels, during which students learn to develop a research protocol and write a manuscript. MECOR Turkiye has been offered every year since 2008. The aim of this paper is to report the number and impact of published articles generated from research questions developed by students in levels 1, 2, and 3 of the ATS MECOR Program in Turkiye between 2008 and 2018. We collected the research questions developed in all levels of the ATS MECOR Program in Turkiye between 2008 and 2018. We searched Google Scholar, PubMed, Web of Science, and ResearchGate in April 2022 to see how many of these research questions were published as articles and, if published, in which journals. Of the 176 research questions collected, 49 had been developed in level 1, 82 had been developed in level 2, and 45 had been developed in level 3. Of those 176 research questions, 55 (31.3%) generated articles that were accepted for publication. The frequency of published articles based on MECOR-developed research questions increased linearly as the course level in which they were developed increased (18.4% in level 1, 30% in level 2, 46.7% in level 3; P = 0.012; linear-by-linear association, P = 0.003). The median time from the development of the research question to publication was three years overall and did not differ significantly among the course levels (P = 0.36). Of the research questions developed, 43 were published in Science Citation Index or Science Citation Index Expanded-indexed journals. Acceptance of an article for publication is one way to measure the impact of the ATS MECOR Program. Our data describe significant research output among our participants, which increases with their length of participation in the program.

Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer

BackgroundHelicobacter pylori infection is a well-known risk factor for gastric cancer. However, the contribution of germline pathogenic variants in cancer-predisposing genes and their effect, when combined with H. pylori infection, on the risk of gastric cancer has not been widely evaluated.MethodsWe evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. We also assessed the combined effect of pathogenic variants and H. pylori infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).ResultsGermline pathogenic variants in nine genes (APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2) were associated with the risk of gastric cancer. We found an interaction between H. pylori infection and pathogenic variants in homologous-recombination genes with respect to the risk of gastric cancer in the sample from HERPACC (relative excess risk due to the interaction, 16.01; 95% confidence interval [CI], 2.22 to 29.81; P=0.02). At 85 years of age, persons with H. pylori infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with H. pylori (45.5% [95% CI, 20.7 to 62.6] vs. 14.4% [95% CI, 12.2 to 16.6]).ConclusionsH. pylori infection modified the risk of gastric cancer associated with germline pathogenic variants in homologous-recombination genes. (Funded by the Japan Agency for Medical Research and Development and others.)

Commonly diagnosed disorders in domestic cats in the UK and their associations with sex and age.

The objectives of this study were to generate a robust evidence base on the prevalence of common disorders in cats and develop a deeper understanding of disorder associations with sex and age that could offer important opportunities for targeted veterinary care to improve feline health and welfare. A random sample of 18,249 cats was obtained from 1,255,130 cats under primary care during 2019 within VetCompass, an epidemiological research programme based on anonymised primary care veterinary clinical records. All disorders recorded during 2019 were extracted and reported, and associations with sex and age were examined. The most prevalent disorders were periodontal disease (n = 2780 [15.2%], 95% confidence interval [CI] 14.72-15.76), obesity (n = 2114 [11.6%], 95% CI 11.12-12.06) and dental disease (n = 1502 [8.2%], 95% CI 7.84-8.64). Compared with male cats, females had an increased prevalence of poor quality of life, postoperative complications and hyperthyroidism, among others. Male cats had a higher prevalence of periodontal disease, road traffic accident (RTA) and obesity. Younger cats (<8 years) had an increased prevalence of cat bite abscess, flea infestation and RTA, while older cats (⩾8 years) had increased prevalence of lameness, cystitis and dental disease, among others. These findings suggest that the veterinary profession needs to engage more effectively in informing owners on common preventable disorders (ie, obesity and dental disease). This new information can contribute to more targeted health surveillance and more effective veterinary interventions to promote improved health and welfare in pet cats. Large-scale collection and analysis of anonymised veterinary clinical records offer an important clinical resource for research.

Association between germline pathogenic variants and breast cancer risk in Japanese women: The HERPACC study.

Approximately 5%–10% of breast cancers are hereditary, caused by germline pathogenic variants (GPVs) in breast cancer predisposition genes. To date, most studies of the prevalence of GPVs and risk of breast cancer for each gene based on cases and noncancer controls have been conducted in Europe and the United States, and little information from Japanese populations is available. Furthermore, no studies considered confounding by established environmental factors and single‐nucleotide polymorphisms (SNPs) identified in genome‐wide association studies (GWAS) together in GPV evaluation. To evaluate the association between GPVs in nine established breast cancer predisposition genes including BRCA1/2 and breast cancer risk in Japanese women comprehensively, we conducted a case‐control study within the Hospital‐based Epidemiologic Research Program at Aichi Cancer Center (629 cases and 1153 controls). The associations between GPVs and the risk of breast cancer were assessed by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models adjusted for potential confounders. A total of 25 GPVs were detected among all cases (4.0%: 95% CI: 2.6–5.9), whereas four individuals carried GPVs in all controls (0.4%). The OR for breast cancer by all GPVs and by GPVs in BRCA1/2 was 12.2 (4.4–34.0, p = 1.74E‐06) and 16.0 (4.2–60.9, p = 5.03E‐0.5), respectively. A potential confounding with GPVs was observed for the GWAS‐identified SNPs, whereas not for established environmental risk factors. In conclusion, GPVs increase the risk of breast cancer in Japanese women regardless of environmental factors and GWAS‐identified SNPs. Future studies investigating interactions with environment and SNPs are warranted.

The Pan African Thoracic Society Methods in Epidemiologic, Clinical and Operations Research Program: A story of success told through a history of publications

Objectives: Despite bearing a substantial burden of respiratory diseases, low- and middle-income countries in Africa contribute little to the research literature. Since 2007, the Pan African Thoracic Society’s Methods in Epidemiologic, Clinical, and Operations Research (PATS-MECOR) program has been working to strengthen capacity in lung health research in Africa. The aim of this study was to assess the research productivity of previous PATS-MECOR participants. Materials and Methods: A systematic review of publications attributed to past PATS-MECOR participants up until 2018 was carried out using a systematic search strategy based on their names on PubMed database. Results: A total of 210 participants drawn from 21 African countries attended PATS-MECOR between 2007 and 2016, of which more than three-quarters (76.7%) had ever published. Of the total 1673 included publications, 303 (12.7%) had multiple course attendees as coauthors. The median publication per published participant was 5 (IQR 2–13) articles. The percentages of the first author, second authors, or last authors publications were 371 (22.2%), 239 (14.3%), and 99 (5.9%), respectively. The top three journals published in were PLOS One 108 (6.6%), Lancet 80 (4.9%), and the International Journal of Tuberculosis and Lung Disease 52 (3.2%). The median citation of their publications was 11 (4–26). There was approximately a double-fold rise in the publication output of participants in their 1st year following attendance to PATS-MECOR compared to the year before the course (123, 68.0% vs. 58, 32.0%). Conclusion: The PATS-MECOR training program has been successful in research capacity building for African investigators as evidenced by a growing publication track record. There is a need to ensure sustainability and for increased collaboration and networking among the trained critical mass of researchers in the continent.

The birth and life of the Pan African Thoracic Society Methods in Epidemiologic, Clinical and Operations Research (PATS MECOR) program: celebrating 15 years

Suggested read for related articles:Better lung health for all: A British Thoracic… May 25, 2021 Bridging the gap in respiratory medicine: How a… January 23, 2021 Management of lung cancer in Africa: Underdiagnosis… September 28, 2021

Building research capacity to correct global health's wrongs

Building research capacity to correct global health's wrongs

Circulating immune- and inflammation-related biomarkers and early-stage noncardia gastric cancer risk.

In Helicobacter pylori-driven gastric cancer, mucosal colonization induces chronic inflammation that may variably progress to cancer. Prospective studies of circulating inflammation-related proteins have suggested weak associations with gastric cancer risk. To assess potential utility as a screening tool in clinical settings, we examined circulating levels of a wide range of key inflammation molecules for associations with early-stage gastric cancer. We used pretreatment EDTA plasma from 239 individuals with early-stage noncardia gastric cancer (203 stage I and 36 stage II) and 256 age-frequency-matched H. pylori-seropositive cancer-free controls within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 92 biomarkers were measured by proximity extension assays using Olink's Proseek Immuno-oncology Panel. Odds ratios (ORs) for association with gastric cancer risk were calculated for quantiles (two to four categories) of each biomarker from unconditional logistic regression models, adjusted for age, sex, smoking and alcohol consumption. Two-sided P values <0.05 were considered as significant. The false discovery rate (FDR) was used to correct for multiple comparisons. Of 83 evaluable biomarkers, lower levels of TNFRSF12A (per quartile OR, 0.82; nominal P-trend = 0.02) and ADGRG1 (per quartile OR, 0.84; nominal P-trend = 0.03) were associated with early-stage gastric cancer but were not statistically significant after FDR correction. Our study did not identify any inflammation-related biomarkers that may be useful for early disease detection. To date, this is the first assessment of circulating inflammation-related proteins in early-stage gastric cancer. Given the complex inflammation processes preceding malignant transformation, further investigation of other biomarkers is warranted.

Associations of circulating mediators of inflammation, cell regulation and immune response with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer globally. The development of squamous cell carcinoma has important inflammatory influences and effects. We, therefore, examined circulating levels of inflammation- and immune-related proteins for associations with ESCC. We used pre-treatment EDTA plasma from 80 ESCC patients (44% clinical stages I and II) and 80 cancer-free control individuals within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 184 biomarkers were measured by high-throughput multiplexed proximity extension assays using Olink's Proseek Cell Regulation and Immuno-Oncology Panels. ESCC odds ratios (OR) per quantile (based on two to four categories) of each biomarker were calculated by unconditional logistic regression models, adjusted for age, sex, cigarette smoking and alcohol consumption. Correlations among continuous biomarker levels were assessed by Spearman's rank correlation. All statistical tests were two-sided with p values < 0.05 considered as significant. Given the exploratory nature of the study, we did not adjust for multiple comparisons. Seven proteins were undetectable in nearly all samples. Of the remaining 177 evaluable biomarkers, levels of cluster of differentiation 40 (CD40, per quartile OR 1.64; p trend = 0.018), syntaxin 16 (STX16, per quartile OR 1.63; p trend = 0.008), heme oxygenase 1 (per quartile OR 1.59; p trend = 0.014), and γ-secretase activating protein (GSAP, per quartile OR 1.47; p trend = 0.036) were significantly associated with ESCC. Amongst these significant markers, levels of CD40, STX16, and GSPA were moderately correlated (Rho coefficients 0.46-0.55; p < 0.05). Our case-control study expands the range of inflammation and immune molecules associated with ESCC. These novel findings warrant replication and functional characterization.

Association between Socioeconomic Status and Digestive Tract Cancers: A Case-Control Study.

Simple SummaryAn association between socioeconomic status (SES) and cancer risk has been reported, but little is known in Asia. We revealed an association between SES, including education level and areal deprivation index (ADI), and digestive tract cancers in Japan. Lower SES was associated with an increased risk of digestive cancers. For stomach cancer, the positive association with ADI disappeared following an additional adjustment of Helicobacter pylori infection and/or atrophic gastritis status. Cancer prevention policy should consider both individual and regional perspectives by the integration of SES in the target population.Although socioeconomic status (SES) has been associated with cancer risk, little research on this association has been done in Japan. To evaluate the association between SES and digestive tract cancer risk, we conducted a case-control study for head and neck, esophageal, stomach, and colorectal cancers in 3188 cases and the same number of age- and sex-matched controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center III (HERPACC III). We employed the education level and areal deprivation index (ADI) as SES indicators. The association was evaluated with odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models adjusted for potential confounders. Even after allowance for known cancer risk factors, the education level showed linear inverse associations with head and neck, stomach, and colorectal cancers. Compared to those educated to junior high school, those with higher education showed statistically significantly lower risks of cancer (0.43 (95% CI: 0.27–0.68) for head and neck, 0.52 (0.38–0.69) for stomach, and 0.52 (0.38–0.71) for colorectum). Consistent with these results for the educational level, the ADI in quintiles showed positive associations with head and neck, esophageal, and stomach cancers (p-trend: p = 0.035 for head and neck, p = 0.02 for esophagus, and p = 0.013 for stomach). Interestingly, the positive association between ADI and stomach cancer risk disappeared in the additional adjustment for Helicobacter pylori infection and/or atrophic gastritis status. In conclusion, a lower SES was associated with an increased risk of digestive cancers in Japan and should be considered in cancer prevention policies for the target population.

AUTOIMMUNE MARKERS FOR PROGRESSION OF LIBBY AMPHIBOLE LAMELLAR PLEURAL THICKENING

SESSION TITLE: Occupational and Environmental Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The Libby Epidemiological Research Program, funded by the Agency for Toxic Substances and Disease Registry, found that autoimmune outcomes were associated with exposure to Libby Asbestiform Amphibole (LAA). THis has been previously published. In addition to the cancers and pulmonary fibrosis typically found with chrysotile asbestos, a highly inflammatory and progressive pleural fibrosis (LPT – lamellar pleural thickening) is frequently found in people exposed to LAA. Progressive LPT can lead to severe pleural pain and/or rapidly worsening pulmonary function. Autoantibodies have been shown to occur in mice and humans exposed to LAA. The purpose of this study was to determine which specific autoantibodies, if any, were related to progressive LPT and to perform sensitivity and specificity testing to determine their usefulness as potential screening markers for progressive disease. METHODS: After IRB approval, a selection of adult patients from the Center for Asbestos Related Diseases (CARD) database was stratified into groups as Progressive LPT, Stable LPT, and no LPT. Participants were required to have had a CT scan of the chest without contrast within the past 2 years as well as a serum sample drawn within 2 years of their CT scan. Two patients each were selected from the Stable LPT and No LPT groups and matched as close as possible to the 19 participants in the Progressive LPT group. Samples were analyzed for ANA (anti-nuclear antibody), MCAA (mesothelial cell autoantibodies), (PLG) Antiplasminogen, Cytokines IL-1beta and IL-17. Afterwards, statistical analysis was applied to determine sensitivity and specificity. RESULTS: ANA was found more frequently in the Progressor group than the Stable or No groups. Positive MCAA was more frequent in the Progressor group, but only statistically greater than the No group. Positive PLG was more frequent in the Progressor group than both the Stable and No groups. IL-1beta and IL-17 had no significant differences between groups. All three antibodies, ANA, MCAA, and PLG, had higher specificity than sensitivity. The most specific test with the strongest predictive values was PLG. When the Stable group was included, none of the three tests had predictive value as a screening test. CONCLUSIONS: Screening for autoimmune markers associated with Progressive PLT might allow early detection and also suggest new therapeutic strategies. The data cited in this study support the association of ANA, MCAA, and PLG with progressive LPT but not stable LPT. CLINICAL IMPLICATIONS: ANA may have some role as a screening tool for risk of severe clinical disease with LPT progression. PLG or MCAA may have some role in predicting progressive LPT, especially when combined with ANA, but while there may be high specificity, sensitivity remains low. Further studies need to validate this finding in women. None of these markers had value in predicting Stable PT. DISCLOSURES: no disclosure on file for Charles Black; No relevant relationships by Tracy McNew, source=Web Response No relevant relationships by Karen Lee Morrissette, source=Web Response No relevant relationships by Jean Pfau, source=Web Response

A standard area diagram set for assessing severity of eucalyptus bacterial blight caused by Erwinia psidii

ABSTRACT This study aimed to develop and validate a standard area diagram (SAD) set to estimate the severity of bacterial blight of eucalyptus caused by Erwinia psidii. For this purpose, an eight-level SAD was developed and validated by ten inexperienced raters. Accuracy and precision of the estimates by each rater, with and without the SAD, were determined based on Lin’s concordance correlation coefficient. The proposed SAD improved the accuracy and precision of the estimates. The SAD set studied here is a useful tool in assessments of bacterial blight of eucalyptus for epidemiological research and breeding programs.

General anesthesia, germ cells and the missing heritability of autism: an urgent need for research.

Agents of general anesthesia (GA) are commonly employed in surgical, dental and diagnostic procedures to effectuate global suppression of the nervous system, but in addition to somatic targets, the subject’s germ cells—from the embryonic primordial stage to the mature gametes—may likewise be exposed. Although GA is generally considered safe for most patients, evidence has accumulated that various compounds, in particular the synthetic volatile anesthetic gases (SVAGs) such as sevoflurane, can exert neurotoxic, genotoxic and epigenotoxic effects, with adverse consequences for cellular and genomic function in both somatic and germline cells. The purpose of this paper is to review the evidence demonstrating that GA, and in particular, SVAGs, may in some circumstances adversely impact the molecular program of germ cells, resulting in brain and behavioral pathology in the progeny born of the exposed cells. Further, we exhort the medical and scientific communities to undertake comprehensive experimental and epidemiological research programs to address this critical gap in risk assessment.

A functional single nucleotide polymorphism in ABCC11, rs17822931, is associated with the risk of breast cancer in Japanese.

The adenosine triphosphate-binding cassette (ABC) transporter superfamily consists of membrane proteins which translocate various substrates across membranes. Because ABCC11, a member ABC transporter, is highly expressed in breast cancer tissue, it may be involved in the efflux of conjugated estrogen metabolites. rs17822931, a functional single nucleotide polymorphism (SNP) in ABCC11, may play a role in the carcinogenesis of breast cancer via estrogen. Here, we aimed to evaluate the association between ABCC11 rs17822931 and breast cancer risk in a Japanese population. We conducted a case-control study in 697 patients with breast cancer and 1394 age- and menopausal status-matched controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center II (HERPACC II). The association was evaluated with odds ratios (ORs) and 95% confidence intervals (CIs) calculated using a conditional logistic model adjusted for potential confounders. In the per allele model, compared with the A allele, the G allele was inversely associated with breast cancer: OR, 0.77, 95% CI, 0.62-0.95 and P = 0.013. The stratified analyses showed that this polymorphism had a high impact on estrogen receptor (ER)-positive breast cancer risk and conditions assumed to correlate with high exposure to estrogen, namely no lactation and low soy intake. Our data showed that a significant association between rs17822931 and the risk of breast cancer, especially ER-positive breast cancer, in Japanese women. Compared to women with low estrogen efflux activity with the A allele, those with high efflux activity with the G allele may have a lower risk of breast cancer, particularly women with high estrogen exposure.

Impact of germinal center-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population.

Germinal center-associated nuclear protein (GANP) is a phosphoprotein involved in mRNA export and regulation of DNA recombination. Although GANP expression in human breast cancer tissue is associated with breast cancer prognosis, the association between the genetic background of GANP and susceptibility and prognosis of breast cancer is unclear. We selected 694 breast cancer cases and 1376 age- and menopausal status-matched non-cancer controls from the Hospitable-based Epidemiologic Research Program, conducted at Aichi Cancer Center between 2001 and 2005. We evaluated the impact of two polymorphisms at the GANP locus (rs2839178 and rs11702450) on the susceptibility and prognosis of breast cancer. Reference alleles were defined as the A allele for rs2839178 and G allele for rs11702450. The GG genotype of rs2839178 was statistically significantly associated with breast cancer risk (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76, P = 0.002). In prognostic analysis, compared to those with AA genotype of rs2839178, patients with AG or GG genotypes had longer disease-free survival (DFS) (hazard ratio [HR] 0.71, 95% CI 0.49-1.04 and HR 0.42, 95% CI 013-1.42, respectively, P for trend = 0.04). eQTL analysis indicated that association with rs2839178 can be explained by the effect of rs2839173 on expression of GANP/MCM3AP. The G allele of rs2839178 at the GANP locus was significantly associated with reduced breast cancer risk and longer DFS in breast cancer patients, showing a consistent direction in the association between susceptibility and clinical outcome. GANP is, therefore, important for the occurrence and progression of sporadic breast cancer.

GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy.

Although recent genome-wide association studies (GWASs) have identified genetic variants associated with Helicobacter pylori (HP)-induced gastric cancer, few studies have examined the genetic traits associated with the risk of HP-induced gastric precancerous conditions. This study aimed to elucidate genetic variants associated with these conditions using a genome-wide approach. Data from four sites of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were used in the discovery phase (Stage I); two datasets from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center 2 (HERPACC2) study were used in the replication phases (Stages II and III) and SKAT (SNP-set Kernel Association Test) and single variant-based GWASs were conducted for the risks of gastric atrophy (GA) and severe GA defined by serum pepsinogen (PG) levels, and PG1 and PG1/2 ratios. In the gene-based SKAT in Stage I, prostate stem cell antigen (PSCA) was significantly associated with the risks of GA and severe GA, and serum PG1/2 level by linear kernel [false discovery rate (FDR) = 0.011, 0.230 and 7.2 × 10-7, respectively]. The single variant-based GWAS revealed that nine PSCA single nucleotide polymorphisms (SNPs) fulfilled the genome-wide significance level (P < 5 × 10-8) for the risks of both GA and severe GA in the combined study, although most of these associations did not reach genome-wide significance in the discovery or validation cohort on their own. GWAS for serum PG1 levels and PG1/2 ratios revealed that the PSCA rs2920283 SNP had a striking P-value of 4.31 × 10-27 for PG1/2 ratios. The present GWAS revealed the genetic locus of PSCA as the most significant locus for the risk of HP-induced GA, which confirmed the recently reported association in Europeans.

Genomewide Association Study of Leisure-Time Exercise Behavior in Japanese Adults.

Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results. We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study. We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples. We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Abstract 1216: Cancer epidemiology research in Vietnam: Current status, challenges and opportunities

Abstract Background: Rapid economic growth, industrialization, and widespread adoption of a Western lifestyle in Vietnam have been accompanied by an emerging epidemic of noncommunicable diseases (NCDs), including cancer. We investigated current status, identified challenges and evaluated opportunities for the development of a comprehensive program in cancer epidemiology research in Vietnam. Methods: We systematically searched OvidMedline, PubMed, and the Cochrane Library for studies published in English on cancer epidemiology in Vietnam prior to November 2017. Data from Vietnam cancer registries were used for descriptive analyses. Technical reports in Vietnamese were also included in our review. Results: Cancer registry data show that by end of 2013, the total number of new cancer cases was 146,457. The most common cancers, in descending order, among men were lung, gastric, colorectal, liver and esophageal cancers while breast, lung, colorectal, gastric and thyroid cancers were the most common cancers among women. Data from six (6) cancer registries during 2004-2013 show that the incidence of several cancers has increased during the past decade, including colorectal cancer (both genders), lung cancer (men), and breast and thyroid cancers (women). Mortality data are limited due to the unavailability of death registries and/or modes of death ascertainment (i.e., causes of death). There is a scarcity of high-quality research on the risk factors (e.g., lifestyle such as smoking, alcohol consumption, physical activity, and BMI, environmental or genetic factors) for cancer in Vietnam. The majority of prior research consists of hospital-based studies (either case-control or cross-sectional designs) with small sample sizes. Since there is no population-based epidemiologic study on cancer in Vietnam, it is difficult to assess temporal trends and risk factors for cancers. Additional challenges include a lack of studies on infectious agents related to cancers and a paucity of molecular or genetic data in cancer, except for a few publications on HBV, HCV, H. Pylori, or EBV or susceptibility genes, such as BRCA1, BRCA2 for breast cancer or GSTA1, GSTP1, GSTT1 and GSTM1 for gastric cancer. Conclusions: Currently, there is no population-based epidemiologic research program for cancer in Vietnam due to the lack of a population-based cancer registry, a dearth of well-trained investigators, and the absence of proper research support infrastructure. This, along with the lack of comprehensive etiologic research in Vietnam, prevents the evaluation of the temporal trends of cancer and risk factors for cancer. The cancer registry has provided important data on cancer incidence; however, there are no data on cancer mortality. Data on molecular and genetic epidemiology of cancer are also limited. These challenges shows the need to develop a comprehensive program in cancer control in Vietnam. Citation Format: Thuan V. Tran, Chi T. Du Tran, Huong T. Tran, Mai V. Nguyen, Mo T. Tran, Quang H. Tran, Thuy Thi-Van Tuong, Martha J. Shrubsole, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu, Linh C. Le, Paolo Boffetta, Hung N. Luu. Cancer epidemiology research in Vietnam: Current status, challenges and opportunities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1216.