Turner A.R.,Center for Cancer Genomics |
Xu J.,Center for Cancer Genomics
Patient Education and Counseling | Year: 2013
Objective: To examine African-American prostate cancer (PCa) survivors' involvement in treatment decision-making (TDM), and examine the association between TDM and quality of life (QOL), using secondary data. Methods: African-American PCa survivors (181) were recruited from the North Carolina Central Cancer Registry. Participants completed a cross-sectional survey that asked about their chosen cancer treatment, TDM factors, and PCa-specific QOL (using the Expanded Prostate Cancer Index Composite - EPIC). Multivariate analysis of covariance was conducted to determine the association between TDM and QOL, controlling for confounders. Results: Most men reported being active (44.2%) or collaborative (38.1%) in TDM, while 14.4% preferred a passive role. Adjusting for marital status, education and treatment, passive patients reported somewhat better QOL compared to active patients in the following QOL domains: urinary summary (p=0.04), urinary function (p=0.01), and urinary incontinence (p=0.03). Conclusion: Most African-American PCa survivors preferred to be, and were, actively or collaboratively involved in TDM. However, those who preferred a passive role reported better PCa-specific QOL for the urinary domain compared to others. Practice implications: It is important to assess patients' TDM preference. Patients' QOL may differ by their TDM role, such that active patients may be more bothered by treatment side effects than other patients. © 2012 Elsevier Ireland Ltd.
PubMed | Fudan University, Center for Cancer Genomics, Chongqing Medical University, Shanghai University and Peking Union Medical College
Type: | Journal: Scientific reports | Year: 2015
Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P=1.7910(-2), OR=1.17, 95% CI=1.03-1.34; rs9267673: P=4.9110(-4), OR=1.37, 95% CI=1.15-1.63; rs2647073: P=3.5310(-5), OR=1.63, 95% CI=1.29-2.06; rs3997872: P=4.2210(-4), OR=1.86, 95% CI=1.32-2.62; rs9275319: P=1.3010(-2), OR=1.32, 95% CI=1.06-1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC.
PubMed | Van Andel Research Institute, Grand Valley Medical Specialists, Spectrum, Duke University and 2 more.
Type: | Journal: Cancer | Year: 2016
Prostate-specific antigen (PSA) screening may reduce death due to prostate cancer but leads to the overdiagnosis of many cases of indolent cancer. Targeted use of PSA screening may reduce overdiagnosis. Multimarker genomic testing shows promise for risk assessment and could be used to target PSA screening.To test whether counseling based on the family history (FH) and counseling based on a genetic risk score (GRS) plus FH would differentially affect subsequent PSA screening at 3 months (primary outcome), a randomized trial of FH versus GRS plus FH was conducted with 700 whites aged 40 to 49 years without prior PSA screening. Secondary outcomes included anxiety, recall, physician discussion at 3 months, and PSA screening at 3 years. Pictographs versus numeric presentations of genetic risk were also evaluated.At 3 months, no significant differences were observed in the rates of PSA screening between the FH arm (2.1%) and the GRS-FH arm (4.5% with GRS-FH vs. 2.1% with FH: This is likely the first randomized trial of multimarker genomic testing to report genomic targeting of cancer screening. This study found little evidence of concern about excess anxiety or overuse/underuse of PSA screening when multimarker genetic risks were provided to patients. Cancer 2016. 2016 American Cancer Society.
PubMed | Shanghai University of Engineering Science, Shanghai JiaoTong University, Center for Cancer Genomics, Fudan University and 2 more.
Type: Journal Article | Journal: Asian journal of andrology | Year: 2016
The [-2]proPSA (p2PSA) and its derivatives, the p2PSA-to-free PSA ratio (%p2PSA), and the Prostate Health Index (PHI) have greatly improved discrimination between men with and without prostate cancer (PCa) in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen (tPSA), free PSA, and p2PSA. For each patient, the free-to-total PSA ratio (%fPSA), PSA density (PSAD), p2PSA-to-free PSA ratio (%p2PSA), and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1 . Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.
Simonds N.I.,U.S. National Institutes of Health |
Khoury M.J.,U.S. National Institutes of Health |
Khoury M.J.,Centers for Disease Control and Prevention |
Schully S.D.,U.S. National Institutes of Health |
And 10 more authors.
Journal of the National Cancer Institute | Year: 2013
A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting the uptake of these tools into clinical practice. Comparative effectiveness research (CER) is intended to generate evidence on the "real-world" effectiveness compared with existing standards of care so informed decisions can be made to improve health care. Capitalizing on funding opportunities from the American Recovery and Reinvestment Act of 2009, the National Cancer Institute funded seven research teams to conduct CER in genomic and precision medicine and sponsored a workshop on CER on May 30, 2012, in Bethesda, Maryland. This report highlights research findings from those research teams, challenges to conducting CER, the barriers to implementation in clinical practice, and research priorities and opportunities in CER in genomic and precision medicine. Workshop participants strongly emphasized the need for conducting CER for promising molecularly targeted therapies, developing and supporting an integrated clinical network for open-access resources, supporting bioinformatics and computer science research, providing training and education programs in CER, and conducting research in economic and decision modeling. © 2013 Published by Oxford University Press.
News Article | November 17, 2016
GRAND RAPIDS, Mich. (Nov. 17, 2016)--Van Andel Research Institute (VARI), in collaboration with Cedars-Sinai, has received a $2.5 million, five-year grant from the National Cancer Institute (NCI), part of the National Institutes of Health, that will fuel efforts by investigators to uncover the underpinnings of cancer, ultimately helping scientists develop better diagnostic and treatment strategies for a class of diseases that claim more than eight million lives each year worldwide. The grant is part of the NCI's Center for Cancer Genomics Genomic Data Analysis Network (GDAN), a federally-funded, nationwide consortium of research and clinical centers all working to better understand how cancer begins, progresses and becomes resistant to treatment. In addition to VARI's award, 12 other groups at top U.S. research organizations were designated as Genome Data Analysis Centers and received funding to conduct additional critical analyses. "We now know that virtually all cancers harbor epigenetic glitches as well as genetic ones," said Peter W. Laird, Ph.D., VARI professor and lead investigator on the GDAN project at the Institute. "If we can precisely define these errors we can then use this information to better classify cancers and to develop new therapeutic strategies that take advantage of these alterations. These types of large-scale, collaborative projects are absolutely essential to ensure we have a clear and comprehensive picture of what's really going on at the most basic level in cancer." Although often thought of as one disease, cancer is actually a diverse group of more than 100 distinct conditions, which makes developing new treatments challenging. Despite their differences, however, all cancers are the result of errors not only in the genetic code itself but also in epigenetics, the mechanisms by which the genetic code is read and acted upon by cells. Laird's team will collaborate closely with Benjamin Berman, Ph.D., at Cedars-Sinai in Los Angeles and with VARI's Hui Shen, Ph.D., to analyze epigenetic data from thousands of samples gathered by GDAN clinical sites around the U.S. and internationally. The data derived from the project will be publicly accessible and available for all scientists to use in the fight against cancer. "Tumors analyzed by the GDAN project will be linked to treatment outcomes and other detailed clinical data from patients, allowing the Genomic Data Analysis Network Centers to identify the molecular changes that are most relevant for clinical decision-making," said Berman. GDAN builds on the success of an earlier project called The Cancer Genome Atlas (TCGA), an NCI effort to define the molecular basis of cancer. Laird, Shen and Berman played integral roles in this consortium, which generated 2.5 petabytes--or 530,000 DVDs worth--of data on samples from more than 11,000 patients across 33 cancers and led to breakthroughs in cancers of the lung, breast and kidneys, among others. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number U24CA210969. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Van Andel Institute (VAI) is an independent nonprofit biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 360 scientists, educators and staff. Van Andel Research Institute (VARI), VAI's research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson's and other diseases and translating those findings into effective therapies. The Institute's scientists work in onsite laboratories and participate in collaborative partnerships that span the globe. Learn more about Van Andel Institute or donate by visiting http://www. . 100% To Research, Discovery & Hope Cedars-Sinai is a national leader in providing high-quality, patient-centered healthcare encompassing primary care as well as specialized medicine and conducting research that leads to life-saving discoveries and innovations. Since its beginning in 1902, Cedars-Sinai has evolved to meet the healthcare needs of one of the most diverse regions in the nation, continually setting new standards in quality and innovation in patient care, research, teaching and community service. Today, Cedars-Sinai is widely known for its national leadership in transforming healthcare for the benefit of patients. Cedars-Sinai impacts the future of healthcare globally by developing new approaches to treatment and educating tomorrow's physicians and other health professionals. At the same time, Cedars-Sinai demonstrates a longstanding commitment to strengthening the Los Angeles community through wide-ranging programs that improve the health of its most vulnerable residents.
Pan L.,Chinese Institute of Basic Medical Sciences |
Zhang L.,U.S. Center for Disease Control and Prevention |
Zhang W.,U.S. Center for Disease Control and Prevention |
Wu X.,Chinese Institute of Basic Medical Sciences |
And 10 more authors.
Human Molecular Genetics | Year: 2014
Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 5-10% of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vaccination. Here, we reported a genome-wide association study in a Chinese Han population consisting of 108 primary high-responders and 77 booster non-responders to hepatitis B vaccination using the Illumina HumanOmniExpress Beadchip. We identified 21 SNPs at 6p21.32 were significantly associated with non-response to booster hepatitis B vaccination (P-value <1 × 10-6). The most significant SNP in the region was rs477515, located ~12 kb upstream of the HLA-DRB1 gene. Its P-value (4.81 × 10-8) exceeded the Bonferroni-corrected genome-wide significance threshold. Four tagging SNPs (rs477515, rs28366298, rs3763316 and rs13204672) that capture genetic information of these 21 SNPs were validated in three additional ChineseHan populations, consisting of 1336 primary high-responders and420 primary non-responders. The fourSNPs continued toshowsignificant associations withnon-response to hepatitis B vaccination (P-combined = 3.98 × 10-13 - 1.42 × 10-8). Further analysis showed that the rs477515 was independently associated with non-response to hepatitis B vaccination with correction for other three SNPs in our GWAS and the known hepatitis B vaccine immunity associated SNP in previous GWAS. Our findings suggest that the rs477515 was an independent marker associated withn on-response to hepatitis B vaccination and HLA-DR region might be a critical susceptibility locus of hepatitis B vaccine-induced immunity. © The Author 2013. Published by Oxford University Press. All rights reserved.
Qu Y.,Fudan University |
Chen H.,Fudan University |
Gu W.,Fudan University |
Gu C.,Fudan University |
And 5 more authors.
Scientific Reports | Year: 2015
Research on sex differences in renal cancer-specific mortality (RCSM), which considered the sex effect to be constant throughout life, has yielded conflicting results. This study hypothesized the sex effect may be modified by age, which is a proxy for hormonal status. Data from the Surveillance, Epidemiology and End Results database (1988-2010) were used to identify 114,539 patients with renal cell carcinoma (RCC). The study cohort was divided into three age groups using cutoffs of 42 and 58 years, which represent the premenopausal and postmenopausal periods. The cumulative incidence function and competing risks analyses were used to examine the effect of covariates on RCSM and other-cause mortality (OCM). In premenopausal period, male sex was a significant predictor of poor RCSM for both localized (adjusted subdistribution hazard ratio [aSHR] = 1.63, P = 0.002) and advanced (aSHR = 1.20, P = 0.041) disease. In postmenopausal period, the sex disparity diminished (aSHR = 1.05, P = 0.16) and reversed (aSHR = 0.95, P = 0.017) in localized and advanced disease, respectively. On the contrary, similar trend was not found for OCM across all age groups. Our results demonstrated the sex effect on RCSM was strongly modified by age. These findings may aid in clinical practice and need further evaluation of underlying biological mechanisms.
Xu J.,Fudan University |
Xu J.,Center for Cancer Genomics |
Sun J.,Center for Cancer Genomics |
Zheng S.L.,Center for Cancer Genomics
Asian Journal of Andrology | Year: 2013
Prostate cancer (PCa) is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is largely unknown but is thought to be multifactorial, where inherited genetics plays an important role. In this article, we first briefly review results from studies of familial aggregation and genetic susceptibility to PCa. We then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. We devote a significant portion of this article to summarizing discoveries of common and low-penetrance PCa risk-associated single-nucleotide polymorphisms (SNPs) from genetic association studies in PCa cases and controls, especially those from genome-wide association studies (GWASs). A strong focus of this article is to review the literature on the potential clinical utility of these implicated genetic markers. Most of these published studies described PCa risk estimation using a genetic score derived from multiple risk-associated SNPs and its utility in determining the need for prostate biopsy. Finally, we comment on the newly proposed concept of genetic score; the notion is to treat it as a marker for genetic predisposition, similar to family history, rather than a diagnostic marker to discriminate PCa patients from non-cancer patients. Available evidence to date suggests that genetic score is an objective and better measurement of inherited risk of PCa than family history. Another unique feature of this article is the inclusion of genetic association studies of PCa in Chinese and Japanese populations. © 2013 AJA, SIMM & SJTU. All rights reserved.
Wang P.,Fudan University |
Ye D.,Fudan University |
Guo J.,Fudan University |
Liu F.,Fudan University |
And 14 more authors.
Genes Chromosomes and Cancer | Year: 2014
Genome-wide association studies have identified 13 single nucleotide polymorphisms (SNPs) that are associated with bladder cancer; three of these SNPs were validated in the Chinese population. This study assessed the performance of these three SNPs, in combination, to predict genetic susceptibility to bladder cancer in Chinese. Three previously established bladder cancer risk-associated SNPs (rs798766 in TACC3, rs9642880 in MYC, and rs2294008 in PSCA) were genotyped in 1,210 bladder cancer patients and 1,008 control subjects in Shanghai, China. A genetic score was calculated for each subject based on these three SNPs. Each of these three SNPs was significantly associated with bladder cancer risk in this independent study population, P < 0.05. The genetic score based on these three SNPs was significantly higher in cases than controls, with a mean of 1.05 and 0.99, respectively, P = 1.03E-05. Compared with subjects with a genetic score <= 1.00, subjects with an elevated genetic score (>1.00) had a significantly increased risk for bladder cancer after adjusting for age, gender, and smoking status, OR = 1.58, 95% Confidence Interval (CI) = 1.21 - 2.06, P = 0.0007. When tested separately for lower (Ta) or higher (Tis, T1-T4) tumor stage, the association was significantly stronger for lower (OR = 2.24, 95% CI = 1.66 - 3.01, P = 1.02E-07) than higher tumor stage (OR = 1.33, 95% CI = 1.00 - 1.78, P = 0.05), P = 0.001. In conclusion, A combination of three previously implicated bladder cancer risk-associated SNPs is a significant predictor of genetic susceptibility to bladder cancer in Chinese.© 2013 Wiley Periodicals, Inc.