Expression of DNA repair genes in ovarian cancer samples: Biological and clinical considerations

Abstract

The purpose of this study was to investigate retrospectively the mRNA expression of genes involved in different DNA repair pathways implicated in processing platinum-induced damage in 171 chemotherapy-naïve ovarian tumours and correlate the expression of the different genes with clinical parameters. The expression of genes involved in DNA repair pathways (PARP1, ERCC1, XPA, XPF, XPG, BRCA1, FANCA, FANCC, FANCD2, FANCF and PolEta), and in DNA damage transduction (Chk1 and Claspin) was measured by RT-PCR in 13 stage I borderline and 77 stage I and 88 III ovarian carcinomas.  


ERCC1, XPA, XPF and XPG genes were significantly less expressed in stage III than in stage I carcinoma; BRCA1, FANCA, FANCC, FANCD2 gene expressions were low in borderline tumours, higher in stage I carcinomas and lower in stage III samples. High levels of ERCC1, XPA, FANCC, XPG and PolEta correlated with an increase in Overall Survival (OS) and Progression Free Survival (PFS), whilst high BRCA1 levels were associated with PFS on univariate analysis.

With multivariate analyses no genes retained an association when adjusted by stage, grade and residual tumour. A tendency towards a better PFS was observed in patients with the highest level of ERCC1 and BRCA1 after platinum-based therapy than those given both platinum and taxol. The expression of DNA repair genes differed in borderline stage I, stage I and stage III ovarian carcinomas. The role of DNA repair genes in predicting the response in ovarian cancer patients seems far from being established.

blog: Taking a Stab at Cost-Effectiveness | Work In Progress

"....With an aim toward making some small step forward in that direction, Cohn et al tried analyzing the cost-effectiveness of Avastin in the treatment of ovarian cancer. (I know I’ve written about Avastin here before, and I don’t mean to pick on this drug, as if it is the richest child on the fancy pharmaceutical playground. This kind of analysis works well here because the high-priced drug acts almost like a caricature for cost considerations in general.)..."

research: Laboratory News | Reversing migratory cancer cells - miR-428

4th Annual OMG! Cancer Summit For Young Adults NYC Apr 16-17th

Research Advocacy Network: 2010 Survey of Advocates Providing Results to Participants in Biospecimen Studies

Contents
Introduction
Overview of Advocate Survey
Survey Results
Summary and Conclusions

"Introduction
If you provided a biospecimen for research
purposes, would you want to know the
results of your individual tests? Would you
want these results only if they had health
implications? Who would you want to
provide you with these results – your
doctor? A genetic counselor? Someone else?..."

full free access: Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries : The Lancet Oncology

Note: there is also chemotherapy-induced secondary cancers (not part of this study) but putting all treatment-related therapies (adverse events) in perspective
--------------------------------------------------------------------------------------------
Interpretation
A relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors, such as lifestyle or genetics.

Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial : The Lancet Oncology

Background

Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain.
We aimed to establish whether colonic stenting has better health outcomes than does emergency surgery.

Vitamin D and Prevention of Cancer — Ready for Prime Time? — NEJM

"Despite biologic plausibility and widespread enthusiasm, the IOM committee found that the evidence that vitamin D reduces cancer incidence and related mortality was inconsistent and inconclusive as to causality.
New trials assessing moderate-to-high-dose vitamin D supplementation for cancer prevention are in progress and should provide additional information within 5 to 6 years.
Although future research may demonstrate clear benefits of vitamin D related to cancer and other nonskeletal health outcomes, and possibly support higher intake requirements, the existing evidence falls short."

Apr 2011(pdf): Cost-Effectiveness of Genetic Screening for Lynch Syndrome (Available at obgmanagement.com)

Supported by
Myriad Genetics Laboratories, Inc

KEY POINTS

• Lynch syndrome is a hereditary predisposition to
colorectal and endometrial cancers (and other specific
malignancies), resulting from a gene mutation
• Lynch syndrome is the most common heritable cause
of colorectal cancer and endometrial cancer
• Practice guidelines limit risk assessment of Lynch syndrome
to 1) genetic testing in people in whom malignancies
have already developed and 2) mitigation of
the impact of disease by colonoscopic and endometrial
surveillance, and surgical prophylaxis
• No primary screening strategies currently exist for Lynch
syndrome
• Over 50% of women with Lynch syndrome who develop
two primary cancers develop a gynecologic cancer
before colon cancer
• Guidelines issued by ACOG recommend that ObGyns
incorporate identification and management of women
who have hereditary breast and ovarian cancer syndrome
into practice; similar guidelines do not exist for
Lynch syndrome
• A new and powerful study has established evidence for
a protocol of primary screening of Lynch syndrome at a
particular threshold of individual risk
• Specifically, primary screening for unaffected patients,
with risk assessment conducted beginning between
25 and 35 years of age, followed by genetic testing of
people whose risk exceeds 5%, has the potential to improve
health outcomes in a cost-effective way

commentary: re: Lengthened WHI Follow-Up: Postmenopausal Estrogen Therapy - Women's Health

full free access: Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy, April 6, 2011— JAMA