OncoLog Volume 40, Number 02, April-June 1995

Creative strategies key in fight against liver cancer Getting patients home and back to their routines more quickly Teaching physicians how to prevent cancerhttps://openworks.mdanderson.org/oncolog/1050/thumbnail.jp

OncoLog Volume 44, Number 12, December 1999

Collaboration Between Scientists, Clinicians Moves Apoptosis Studies Forward Answering the Who, What, and How of Medical Physics USHERING IN NEW TECHNOLOGIES: Medical Physicists Focus on IMRT, Ultrasound-Guided Brachytherapy DiaLog: Building Better Patient Care on the Foundation of Scientific Research, by John Mendelsohn, MD, President, Professor of Clinical Investigation House Call: Make Cancer Prevention Part of Your New Year\u27s Resolutionshttps://openworks.mdanderson.org/oncolog/1080/thumbnail.jp

OncoLog Volume 45, Number 06, June 2000

Newly Organized Ophthalmology Section Expands Treatment of Ocular Malignancies Turning Knowledge Into Effective Gene Therapies, by Jack A. Roth, MD, Professor, Department of Thoracic and Cardiovascular Surgery, and Gary S. Clayman, MD, DDS, Associate Professor, Head and Neck Surgery Microarrays Reduce Time, Labor, and Cost of DNA Analysis New DNA Microarray Technology Could Speed Up Discovery of the Genetic Causes of Lung Cancer House Call: Virtual Health: Finding Reliable Medical Resources on the Internet Clinical Practice Guidelines: Case Report: Ovarian Cancer Protocols: Studies Aim to Detect and Treat Ocular Malignancieshttps://openworks.mdanderson.org/oncolog/1086/thumbnail.jp

MTHFR polymorphisms in relation to ovarian cancer risk

Objective Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. Methods We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses’ Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY). Results Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T ptrend = 0.59 and A1298C ptrend = 0.58). Significant associations (C677T ptrend=0.001, A1298C ptrend=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies. Conclusions MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium

We previously reported risks of ovarian carcinoma for common polymorphisms in one-carbon (1-C) transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990 and TYMS rs495139 with risk of ovarian carcinoma overall, and to utilize the large sample of assembled cases to investigate associations by histological type

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

Impact of Activity-Based Therapy on Respiratory Outcomes in a Medically Complex Child

Introduction: Activity-based therapies (ABTs) focus on activating the neuromuscular system below the level of spinal cord injury (SCI) promoting neuromuscular capacity. Case description: A 2 year 7 month old with history of prematurity at 29 weeks, neonatal epidural abscess, resultant cervical SCI, respiratory failure, and global developmental delays presented for enrollment in an outpatient activity-based therapy program. Upon presentation to this program, he required nighttime mechanical ventilation via tracheostomy and daytime suctioning. He could not perform any age-appropriate activities and was described by his mother as ‘present’, neither engaged nor attentive. During and after 7 months of participation in ABTs including locomotor training and neuromuscular electrical stimulation, the patient demonstrated unexpected changes in his respiratory status leading to ventilator weaning with concomitant improvements in head and trunk control, participation, development, and quality of life. Discussion: ABT was not only safe for a medically complex child, but also this intervention had a remarkable effect on unresolved respiratory capacity and a more widespread impact on other functions as well as development. A child with a chronic, severe SCI demonstrated positive and impactful improvements in health, functional status, and quality of life during an episode of ABT