OVARIAN CANCER and US: hereditary

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Showing posts with label hereditary. Show all posts
Showing posts with label hereditary. Show all posts

Sunday, May 06, 2012

Epigenetic modification and cancer: mark or stamp? (BRCA/fallopian tube....)



Epigenetic modification and cancer: mark or stamp?

Abstract

Hypotheses are built upon data, but data require hypotheses before they can be understood. The development of the ‘two-hit’ hypothesis of carcinogenesis was a key event in cancer genetics because it provided a testable model of how tumours develop. In this commentary on ‘Promoter hypermethylation patterns in Fallopian tube epithelium of BRCA1 and BRCA2 germline mutation carriers’ by Bijron et al. published in the February 2012 issue of Endocrine-Related Cancer, the need for new grammar and some new hypotheses in epigenetics is discussed. Meanwhile, data suggesting an important role of epigenetic modification in the cause, progression and treatment of cancer continues to accumulate............

Introduction

In hereditary tumours, the first hit occurs in the germ line, whereas in non-hereditary tumours, the first hit occurs in the cell from which the tumour arises. The second hits are always somatic, and can inactivate the second allele in various different ways. The development of the ‘two-hit’ hypothesis of carcinogenesis was a key event in cancer genetics because it provided a testable model of how tumours develop (Knudson 1971, 1978). Although there have been extensions and revisions to the basic model (Tomlinson et al. 2001), the essential elements of the basic hypothesis remain intact, 40 years on. In the original ‘test case’ of RB-1 mutations in retinoblastoma, these events were physical alterations in the structure of the chromosome or gene (Cavenee et al. 1983), and the perception was such that physical changes put a ‘stamp’ on the tumour that could be detected by examination of genomic DNA.............
continue to read full paper

Tuesday, January 17, 2012

abstract: Uterine Serous Carcinoma: Increased Familial Risk for Lynch-Associated Malignancies.



Abstract

Purpose:
Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for serous uterine carcinoma patients, focusing on Lynch syndrome malignancies.
CONCLUSIONS: We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of serous cancer patients in a single institution study. Follow-up studies suggest only pancreatic cancers are over-represented in relatives. DNA mismatch repair defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers.

Monday, July 18, 2011

Risk for CRC in Lynch Syndrome May Be Lower Than We Thought: Prevalence of Alterations in DNA Mismatch Repair Genes in Patients With Young-Onset Colorectal Cancer - Medscape Oncology



"Clearly, as we develop more accurate estimates of risks associated with specific mutations, personalized screening methods and intervals will need to be further clarified among those with LS. Although it appears that the overall risk for CRC among those with LS may be lower than previously thought, there are likely to be specific mutations that confer a higher risk and require more intensive screening protocols."

Factors Associated with Altered Long-Term Well-Being After Prophylactic Salpingo-Oophorectomy Among Women at Increased Hereditary Risk for Breast and Ovarian Cancer-abstract




Monday, March 14, 2011

Gastroenterology & Endoscopy News - Gastros Outperform Oncologists in Recognition of Inherited CRC (Lynch Syndrome/PJS/FAP....extracolonic tumors)



Note: access is free/requires registration

"......Overall, physicians benefited from the educational intervention, scoring significantly higher on exams about genetic testing for Lynch syndrome, FAP and Peutz-Jeghers syndrome post-test than at baseline. The education session also significantly improved physicians’ recognition of Lynch syndrome family pedigrees and surveillance of the disease, but did not effectively enhance awareness of extra-colonic manifestations.

Although the educational intervention improved the ability of physicians to identify families with multiple members affected by CRC, it did not help them spot extra-colonic cancers in families with Lynch syndrome. Identifying extra-colonic cancers is important because Lynch syndrome increases a person’s risk for endometrial cancer and is associated with cancers of the stomach (6%-9%); ovaries (6%-12%); and ureter and renal pelvis (3%-8%) (and others), according to the Colon Cancer Alliance for Research and Education for Lynch Syndrome...........cont'd

"Ms. (Kate) Murphy has survived ovarian and breast cancer as well as three episodes of colon cancer."

Sunday, October 10, 2010

recruiting: Clinical Outcomes in Hereditary Cancer - Full Text View - ClinicalTrials.gov BRCA/pancreatic/breast



Purpose

Compare the clinical characteristics and post-surgical outcomes (overall survival)of pancreatic cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 .

Compare the clinical characteristics and outcomes (time to progression) of breast cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 receiving paclitaxel chemotherapy for metastatic disease.

Sunday, September 26, 2010

(repeat) abstract: SGO White Paper on ovarian cancer: etiology, screening and surveillance



Abstract: Ovarian cancer is a heterogeneous, rapidly progressive, highly lethal disease of low prevalence. The etiology remains poorly understood. Numerous risk factors have been identified, the most prominent involving an inherited predisposition in 10% of cases. Women with germline mutations associated with Hereditary Breast/Ovarian Cancer and Lynch syndromes have dramatically elevated risks (up to 46% and 12%, respectively). Risk-reducing salpingo-oophorectomy is the best method to prevent ovarian cancer in these high-risk women. Significant risk reduction is also seen in the general population who use oral contraceptives. Since up to 89% patients with early-stage disease have symptoms prior to diagnosis, increased awareness of the medical community may facilitate further workup in patients who otherwise would have had a delay. Despite enormous effort, there is no proof that routine screening for ovarian cancer in either the high-risk or general populations with serum markers, sonograms, or pelvic examinations decreases mortality. Further evaluation is needed to determine whether any novel biomarkers, or panels of markers, have clinical utility in early detection. Prospective clinical trials have to be designed and completed prior to offering of any of these new diagnostic tests. CA125 is currently the only biomarker recommended for monitoring of therapy as well as detection of recurrence. This commentary provides an overview on the background, screening and surveillance of ovarian cancer.

Sunday, September 12, 2010

Genetic profiles distinguish different types of hereditary ovarian cancer



Abstract:

Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) (Lynch Syndrome) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles, with an average 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17 and 19 characterized the HNPCC tumors, but target genes herein are unknown.
The results indicate that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.

Monday, September 06, 2010

Methylation profiles of hereditary and sporadic ovarian cancer - Histopathology - abstract



Conclusions: 

 CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes

Saturday, May 22, 2010

Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk...



Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk Education Intervention Tool (CREdIT)

Tuesday, March 30, 2010

Creighton University Dr Henry Lynch Earns National Award for Lifetime Work in Hereditary Cancer



"Lynch has long been considered a pioneer in the field of hereditary cancer research and prevention. As an internal medicine resident in the 1960s, Lynch met patients who had many family members who were affected by or had died from the same type of cancer; he hypothesized the cancer could be triggered by hereditary factors. That launched a lifelong pursuit to uncover genetic links to certain types of cancer that, at the time, his peers thought to be triggered almost solely by environmental causes.

In the 1970s, Lynch was the first to describe a hereditary breast ovarian cancer syndrome, findings that led to the identification of the BRCA1 and BRCA2 germline mutations that predispose women to this syndrome. Hereditary nonpolyposis colorectal cancer (HNPCC), the most common form of hereditary colorectal cancer, is named after him as the Lynch syndrome."

Wednesday, March 10, 2010

A High Proportion of DNA Variants of BRCA1 and BRCA2 Is Associated with Aberrant Splicing in Breast/Ovarian Cancer Patients



Conclusions: An important fraction of DNA variants of BRCA1/2 presents splicing aberrations that may represent a relevant disease-causing mechanism in HBOC.

Thursday, March 04, 2010

Obstetrics/Gynecology Residents' Knowledge of Hereditary Breast and Ovarian Cancer and Lynch Syndrome.



"Although there have been many studies regarding physicians' knowledge of hereditary cancer syndromes, very little information exists regarding medical residents' knowledge of hereditary cancer syndromes. Obstetrics/gynecology residents completed a test which evaluated their knowledge of hereditary breast and ovarian cancer and Lynch syndrome.

Wednesday, March 03, 2010

Hereditary Ovarian Cancer: Molecular Genetics, Pathology, Management, and Heterogeneity



Future Prospects: DNA Variants Modify HBOC and LS (Lynch Syndome) Cancer Risk:
What does the future hold with respect to molecular genetics and cancer control in hereditary cancer, inclusive of HBOC and Lynch syndrome?

This projection relates to the truism that cancer-causing mutations do not act in a vacuum, since they are likely to be impacted by additional low-penetrant modifier genes in concert with myriad environmental events.