Heritable interleukin-17F (IL17F) gene variation and overall survival (OS) in pancreatic cancer patients (pts): Results from a genome-wide association study (GWAS) in CALGB 80303

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4531-4531
Author(s):  
F. Innocenti ◽  
K. Owzar ◽  
N. Cox ◽  
P. Evans ◽  
M. Kubo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genome Wide Association Study ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Rank Test ◽  
Chromosome 15 ◽  
Heritable Variation ◽  
Primary Analysis ◽  
Genome Wide ◽  
A Genome

4531 Background: CALGB 80303 was a randomized, phase III study in 602 advanced pancreatic cancer (PC) pts treated with gemcitabine plus either bevacizumab or placebo. No difference in OS was observed between the two arms (Kindler, ASCO 2007). As part of the study, we prospectively collected germline DNA for pharmacogenetic studies, originally focusing on the association of candidate genes with OS and toxicity. We subsequently amended the study to conduct a GWAS in order to identify other associations. Methods: Germline DNA was isolated from peripheral blood on 352 pts, and was typed for more than 550,000 SNPs using the Illumina550 platform. The associations between OS and SNPs were investigated using the log-rank test. A review of the clinical data and ancestry genomic analysis identified 294 pts who were clinically eligible and determined to be genetically European, and this subset was used for the primary analysis. Results: For the analysis of OS, pts in both arms were pooled, and two SNPs were associated with OS using genome-wide criteria (p≤10–7). This included an intergenic SNP on chromosome 15 (rs7174643), and a nonsynonymous SNP in the IL17F gene ( rs763780 ) with an allelic frequency of 3.9% (H161R, p<2.7x10–8). Median OS was significantly shorter for the H/R heterozygotes (3.1 months, 95% CI 2.3–4.3, n=23), as compared to the H/H homozygotes (6.8 months, 95% CI 5.8–7.3, n=271). This association remained highly significant when the analysis was stratified by extent of disease or previous radiotherapy. There was no evidence of an interaction with bevacizumab, suggesting that this SNP is prognostic rather than predictive. Conclusions: Heritable variation in IL17F may be a prognostic marker for PC. Wildtype (161H) IL17F is a pro-inflammatory, anti-angiogenic cytokine (Starnes, J Immunol 2001). The 161R mutant IL17F antagonizes wildtype IL17F (Kawaguchi, J Allergy Clin Immunol, 2006), potentially resulting in a pro-angiogenic effect. Replication studies in PC and other solid tumors are indicated. [Table: see text]

Survival outcomes of advanced pancreatic cancer in an integrative treatment setting: The Cancer Treatment Centers of America experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15188-15188
Author(s):  
C. G. Lis ◽  
R. D. Levin ◽  
R. Neelam ◽  
P. G. Vashi ◽  
C. A. Lammersfeld ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Treatment ◽  
Median Survival ◽  
Advanced Pancreatic Cancer ◽  
Treatment Protocol ◽  
Phase Iii ◽  
Definitive Treatment ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Survival Outcomes

15188 Background: In this study, we report the survival outcomes of patients with advanced pancreatic cancer who underwent intra- arterial mitomycin/cisplatin therapy at Cancer Treatment Centers of America (CTCA), a community hospital comprehensive cancer center combining conventional and integrative medical therapies. Methods: At our center, all patients undergo a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support while receiving an aggressive conventional treatment protocol. Using data collected by the cancer registry, we identified 114 consecutively treated newly diagnosed cases of invasive pancreatic cancer who underwent definitive treatment between Jan 01 and Dec 05. Results: 26 patients were stage III and 88 were stage IV. The median age was 58 years (range 31 to 81 years). 55 patients were selected for intra-arterial therapy with mitomycin/cisplatin. These patients had a PS of 2 or better and either had no metastatic lesions or a single localized liver metastasis. 16 patients in this cohort received radiotherapy. The 59 other patients underwent a variety of therapies. Intra-arterially treated patients had a median survival of 369 days and a 2-year cumulative survival of 19%. Patients not treated with intra-arterial therapy had a median survival of 249 days and a 2-year survival of 11%. Univariate survival analysis found that patients undergoing intra-arterial therapy had significantly better survival outcomes compared to patients undergoing different therapies (Log rank test P = 0.04). The table compares the survival outcomes of recent phase III investigations on first line therapies for pancreatic cancer with those at CTCA. Conclusion: Currently, the published clinical trial data in advanced pancreatic indicates a one-year survival ranging from less than 10% to 28%. Consequently, the survival outcomes of patients undergoing therapy at our center warrant further investigation. [Table: see text] No significant financial relationships to disclose.

scholarly journals Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials

2018 ◽  
Vol 25 (4) ◽  
pp. 565-573 ◽  
Author(s):  
Dorothea Buck ◽  
Till FM Andlauer ◽  
Wilmar Igl ◽  
Eva-Maria Wicklein ◽  
Mark Mühlau ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Variants ◽  
Neutralizing Antibodies ◽  
Genome Wide Association Study ◽  
Phase Iii ◽  
Interferon Β ◽  
Hla Alleles ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. Objective: To validate the proposed genetic markers and to identify new markers. Methods: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron®/BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials. All patients were treated with interferon β-1b for at least 6 months. In addition, a genome-wide association study was conducted to identify new genetic variants. Results: We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10−4) and HLA-DRB1*07:01 (OR = 1.8, p = 3.5 × 10−3) for developing neutralizing antibodies (NAbs). Several additional, previously proposed HLA alleles and genetic variants showed nominally significant associations. In the exploratory analysis, variants in the HLA region were associated with NAb development at genome-wide significance (OR = 2.6, p = 2.30 × 10−15). Conclusion: The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies.

scholarly journals A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

2010 ◽  
Vol 42 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Gloria M Petersen ◽  
Laufey Amundadottir ◽  
Charles S Fuchs ◽  
Peter Kraft ◽  
Rachael Z Stolzenberg-Solomon ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Cancer Susceptibility ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness

2020 ◽  
Vol 105 (10) ◽  
pp. 3203-3214 ◽  
Author(s):  
Andrew Dauber ◽  
Yan Meng ◽  
Laura Audi ◽  
Sailaja Vedantam ◽  
Benjamin Weaver ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Primary Analysis ◽  
Pharmacogenetic Study ◽  
Genome Wide ◽  
A Genome ◽  
Secondary Analyses ◽  
Genome Wide Significance

Abstract Context Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. Objective To identify genetic variants associated with GH responsiveness. Design Genome-wide association study (GWAS). Setting Cohorts from multiple academic centers and a clinical trial. Patients A total of 614 individuals from 5 short stature cohorts receiving GH: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age. Intervention Association of more than 2 million variants was tested. Main Outcome Measures Primary analysis: individual single nucleotide polymorphism (SNP) association with first-year change in height standard deviation scores. Secondary analyses: SNP associations in clinical subgroups adjusted for clinical variables; association of polygenic score calculated from 697 genome-wide significant height SNPs with GH responsiveness. Results No common variant associations reached genome-wide significance in the primary analysis. The strongest suggestive signals were found near the B4GALT4 and TBCE genes. After meta-analysis including replication data, signals at several loci reached or retained genome-wide significance in secondary analyses, including variants near ST3GAL6. There was no significant association with variants previously reported to be associated with GH response nor with a polygenic predicted height score. Conclusions We performed the largest GWAS of GH responsiveness to date. We identified 2 loci with a suggestive effect on GH responsiveness in our primary analysis and several genome-wide significant associations in secondary analyses that require further replication. Our results are consistent with a polygenic component to GH responsiveness, likely distinct from the genetic regulators of adult height.

scholarly journals Genetic polymorphisms associated with pancreatic cancer survival: a genome-wide association study

2017 ◽  
Vol 141 (4) ◽  
pp. 678-686 ◽  
Author(s):  
Hongwei Tang ◽  
Peng Wei ◽  
Ping Chang ◽  
Yanan Li ◽  
Dong Yan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Association Study ◽  
Genetic Polymorphisms ◽  
Genome Wide Association Study ◽  
Cancer Survival ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study of Overall Survival in Pancreatic Cancer Patients Treated with Gemcitabine in CALGB 80303

2011 ◽  
Vol 18 (2) ◽  
pp. 577-584 ◽  
Author(s):  
Federico Innocenti ◽  
Kouros Owzar ◽  
Nancy L. Cox ◽  
Patrick Evans ◽  
Michiaki Kubo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Association Study ◽  
Cancer Patients ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-Wide Association Analysis of Neonatal White Matter Microstructure

2020 ◽  
Author(s):  
J Zhang ◽  
K Xia ◽  
M Ahn ◽  
S C Jha ◽  
R Blanchett ◽  
...  
Keyword(s):  
White Matter ◽  
Genome Wide Association Study ◽  
Diffusion Tensor ◽  
Axon Growth ◽  
Genome Wide Association ◽  
Joint Analysis ◽  
Heritable Variation ◽  
White Matter Microstructure ◽  
Genome Wide ◽  
A Genome

ABSTRACT A better understanding of genetic influences on early white matter development could significantly advance our understanding of neurological and psychiatric conditions characterized by altered integrity of axonal pathways. We conducted a genome-wide association study (GWAS) of diffusion tensor imaging (DTI) phenotypes in 471 neonates. We used a hierarchical functional principal regression model (HFPRM) to perform joint analysis of 44 fiber bundles. HFPRM revealed a latent measure of white matter microstructure that explained approximately 50% of variation in our tractography-based measures and accounted for a large proportion of heritable variation in each individual bundle. An intronic SNP in PSMF1 on chromosome 20 exceeded the conventional GWAS threshold of 5 x 10−8 (p = 4.61 x 10−8). Additional loci nearing genome-wide significance were located near genes with known roles in axon growth and guidance, fasciculation, and myelination.

Sign in / Sign up

Export Citation Format

Share Document