187 research outputs found
Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer
Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P= 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary. © 2001 Cancer Research Campaign http://www.bjcancer.co
Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer : a case-control study in a population with relatively low folate intake
Peer reviewedPublisher PD
Efficacy of early diagnosis and treatment in women with a family history of breast cancer
BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality. METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan—Meier survival plots. RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first (“prevalence”) round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+. CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of “breast awareness” as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.publishedVersio
Ethical, social and economic issues in familial breast cancer: a compilation of views from the EC biomed II demonstration project
ABSTRACT:
Demand for clinical services for
familial breast cancer is continuing to rise across
Europe. Service provision is far from uniform and, in
most centres, its evolution has been determined by
local conditions, specifically by local research
interests, rather than by central planning. However, in
a number of countries there is evidence of progress
towards co-ordinated development and audit of clinics
providing risk assessment, counselling, screening and,
in some cases, prophylactic intervention. Much
important information should emerge from continued
observation and comparative assessment of these
developments.
In most countries for which relevant data are
available, there is a distinct bias towards higher social
class among those who avail themselves of clinic
facilities (in line with findings from many other
health-promotion initiatives). This should be
addressed when considering future organisation of
clinical services.
Molecular genetic studies designed to identify the
underlying mutations responsible for familial breast
cancer are not generally regarded as part of the clinical
service and are funded through research grants (if at
all). Economic considerations suggest that there is a
case for keeping this policy under review.
Familial cancers throw into sharp relief certain ethical
and legal issues that have received much recent
attention from government advisory bodies, patients
’
representatives, professional commentators and the
popular media. Two are of particular importance;
first, the right to gain access to medical records of
relatives, in order to provide accurate risk assessment
for a given family member, versus the right to privacy
in respect of personal medical information and,
second, the obligation (or otherwise) to inform family
members of their risk status if they have not actively
sought that knowledge. The legal position seems to
vary from country to country and, in many cases, is
unclear. In view of pressures to establish uniform
approaches to medical confidentiality across the EC, it
is important to evaluate the experience of participants
in this Demonstration Programme and to apply the
principle of
“
non-malfeasance
”
in formulating regu-
lations that should govern future practice in this field.
Data on economic aspects of familial breast cancer are
remarkably sparse and outdated. As evidence accrues
on the influence of screening and intervention
programmes on morbidity and mortality, there is a
strong case for evaluating the cost-effectiveness of
different models of service provisi
Chapter 16 - Cross-cutting investment and finance issues
This is the first time an assessment report by the Intergovernmental Panel on Climate Change (IPCC) contains a chapter dedicated to investment and finance to address climate change. This reflects the growing awareness of the relevance of these issues for the design of efficient and effective climate policies
Colorectal cancer genomics: evidence for multiple genotypes which influence survival
Colorectal cancer (CRC) is a leading cause of cancer death and the mechanism for variable outcome in this disease is not yet fully understood. It is hypothesized that differences in the genetic make-up of tumours may be partially responsible for the differences observed in survival among same staged individuals for this disease. In this study the tumour genomes of 29 consecutive patients undergoing surgery for Dukes' C CRC were assessed by comparative genomic hybridization (CGH). In addition, the CGH profiles from the tumours were compared with those from eight colorectal cell lines. Great variation in genetic grade (all detectable aberrations i.e., loss + gain) was observed in 29 Dukes' C colorectal tumours by CGH (median four aberrations per tumour, range 0–20). Gain was found in 76% and loss in 41% of tumours. The most frequently observed regions of gain were 13q (27.6%), 20q (27.6%), 7p (24.1%), 8q (24.1%), and 1q (20.7%) and loss were 18q (31%), 4q (20.7%), 17p (20.7%), 18p (20.7%), and 15q (20.1%). None of these specific genomic aberrations were associated with patient survival. However, patients with more than two aberrations had a better survival than patients with fewer regions of loss and gain (P = 0.02). CRC cell lines had similar regions of loss or gain as the tumours. However, the frequency of genomic aberrations was much greater in the CRC cell lines. Although genomic change in CRC is relevant to the survival of patients with Dukes' C CRC, careful analysis is required to identify cell lines which are representative models of CRC genomics.© 2001 Cancer Research Campaign http://www.bjcancer.co
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Utilisation of prophylactic mastectomy in 10 European centers
ABSTRACT:
Increasingly women at high risk of
breast cancer are opting for prophylactic surgery to
reduce their risks. Data from 10 European centres that
offer a risk counselling and screening service to
women at risk show different approaches to the option
of preventive surgery, although most centres adhere to
a protocol including at least two risk counselling
sessions and a psychological assessment. Thus far the
combined centres have data on 174 women who have
undergone prophylactic mastectomy with in excess of
400 women years of follow up. Operations were
carried out on women with lifetime risks of 25–80%,
with an average annual expected incidence rate of 1%
per women. No breast cancers have occurred in this
cohort. Long term follow up on an extended group of
women will be necessary to truly address the risk of
subsequent breast cancer and the psychological
sequelae
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