Unique Breast Cancer Features Within the Vietnamese Population

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts. PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population. METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year period. We recorded the subtype of breast cancer, tumor grade, age at diagnosis, and menopausal status for each woman. We then compared these characteristics between our population of Vietnamese breast cancer patients, and an ethnically diverse group of American women from the 2010 SEER registry. RESULTS: We discovered that 15 of 33 Vietnamese patients diagnosed in our breast center had HER2 over-expressing breast cancer, resulting in a 45% rate of HER2 positivity. Compared with the 2010 Surveillance, Epidemiology, and End Results (SEER) registry data that encompasses 28% of all US breast cancer patients diagnosed that year, regardless of race, the Smith Clinic Vietnamese cohort had a statistically significant higher rate of HER2+ breast cancer, with an odds ratio of 4.7 (45% vs. 15%, p CONCLUSIONS: Vietnamese breast cancer patients, especially those older than 50 years old, tend to have higher rates of HER2+ breast cancer than the general population. This unique pattern of breast cancer merits further study, as it may reflect a genetic mutation or environmental exposure which is more common among Vietnamese women

Quantifying the impact of community quarantine on SARS transmission in Ontario: estimation of secondary case count difference and number needed to quarantine

<p>Abstract</p> <p>Background</p> <p>Community quarantine is controversial, and the decision to use and prepare for it should be informed by specific quantitative evidence of benefit. Case-study reports on 2002-2004 SARS outbreaks have discussed the role of quarantine in the community in transmission. However, this literature has not yielded quantitative estimates of the reduction in secondary cases attributable to quarantine as would be seen in other areas of health policy and cost-effectiveness analysis.</p> <p>Methods</p> <p>Using data from the 2003 Ontario, Canada, SARS outbreak, two novel expressions for the impact of quarantine are presented. Secondary Case Count Difference (SCCD) reflects reduction in the average number of transmissions arising from a SARS case in quarantine, relative to not in quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative binomial regression models (with identity link function) comparing the number of secondary cases to each index case for quarantine relative to non-quarantined index cases. The inverse of this statistic is proposed as the number needed to quarantine (NNQ) to prevent one additional secondary transmission.</p> <p>Results</p> <p>Our estimated SCCD was 0.133 fewer secondary cases per quarantined versus non-quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in community quarantine to prevent one additional case of transmission in the community. This analysis suggests quarantine can be an effective preventive measure, although these estimates lack statistical precision.</p> <p>Conclusions</p> <p>Relative to other health policy areas, literature on quarantine tends to lack in quantitative expressions of effectiveness, or agreement on how best to report differences in outcomes attributable to control measure. We hope to further this discussion through presentation of means to calculate and express the impact of population control measures. The study of quarantine effectiveness presents several methodological and statistical challenges. Further research and discussion are needed to understand the costs and benefits of enacting quarantine, and this includes a discussion of how quantitative benefit should be communicated to decision-makers and the public, and evaluated.</p

Excess mortality associated with eating disorders : a population-based cohort study.

Background Individuals with eating disorders (EDs) have a high mortality risk. Few population-based studies have estimated mortality risk in EDs other than anorexia nervosa. Aims To investigate all-cause mortality within a population-based cohort of individuals who received hospital-based care for any ED (anorexia nervosa, bulimia nervosa or ED not otherwise specified) in Ontario, Canada. Methods We conducted a retrospective-cohort study of 19,041 individuals with an ED from January 1, 1990, to December 31, 2013 using administrative healthcare data. The outcome of interest was death. Excess mortality was assessed using standardized mortality ratios (SMRs) and potential years of life lost (PYLL). Cox proportional hazards regression models were used to examine socio-demographic and medical comorbidities associated with greater mortality risk. Results The ED cohort had 17,108 females (89.9%) and 1,933 males (10.1%). The all-cause mortality for the entire ED cohort was five times higher than expected compared to the Ontario population (SMR = 5.06; 95% CI:4.82-5.30). SMRs were higher for males (SMR=7.24; 95% CI: 6.58- 7.96) relative to females (SMR=4.59; 95% CI: 4.34-4.85), overall and in all age groups in the cohort. For both sexes, the ED cohort PYLL was more than 6 times higher than the expected PYLL in the Ontario population. Conclusions and Relevance Patients with EDs experience five to seven times higher mortality rates compared to the overall population. There is an urgent need to understand the mortality risk factors to improve health outcomes among individuals with eating disorders

Moderate to severe gambling problems and traumatic brain injury: A population-based study

Traumatic brain injury (TBI) is a common injury characterized by a change in brain function after an external blow to the head and is associated with substance abuse, psychological distress, risk-taking, and impulsivity. Convenience and clinical samples have also linked TBI to problem gambling, but have not ruled out confounding variables such as hazardous drinking and psychological distress. This study examines the relationship between TBI and moderate to severe problem gambling in a general population probability sample controlling for hazardous drinking and psychological distress. The data were obtained from a 2015–2016 cross-sectional general population telephone survey of adults ages 18+from Ontario, Canada (N = 3809). Logistic regression was used to estimate the association as adjusted odds ratios (AOR). Moderate to severe problem gambling was independently associated with a history of TBI after adjusting for potential confounders (AOR: 2.80), and had a statistically significant relationship with psychological distress (AOR = 2.74), hazardous drinking (AOR = 2.69), and lower educational levels (AOR = 0.37). This study provides further data to suggest a link between TBI and moderate to severe problem gambling; however, more research is needed to determine if there is a causal relationship or the potential implications for prevention and treatment

Moderate to severe gambling problems and traumatic brain injury: A population-based study

Traumatic brain injury (TBI) is a common injury characterized by a change in brain function after an external blow to the head and is associated with substance abuse, psychological distress, risk-taking, and impulsivity. Convenience and clinical samples have also linked TBI to problem gambling, but have not ruled out confounding variables such as hazardous drinking and psychological distress. This study examines the relationship between TBI and moderate to severe problem gambling in a general population probability sample controlling for hazardous drinking and psychological distress. The data were obtained from a 2015–2016 cross-sectional general population telephone survey of adults ages 18+from Ontario, Canada (N = 3809). Logistic regression was used to estimate the association as adjusted odds ratios (AOR). Moderate to severe problem gambling was independently associated with a history of TBI after adjusting for potential confounders (AOR: 2.80), and had a statistically significant relationship with psychological distress (AOR = 2.74), hazardous drinking (AOR = 2.69), and lower educational levels (AOR = 0.37). This study provides further data to suggest a link between TBI and moderate to severe problem gambling; however, more research is needed to determine if there is a causal relationship or the potential implications for prevention and treatment

Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (,0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned

Inherited variation in immune genes and pathways and glioblastoma risk

To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel–Haenzel P values = 1 × 10−5 to 4 × 10−3), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion–extravasation–migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.Includes NIHR and CRUK

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

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