abstract: (Lynch Syndrome) Colorectal and Other Cancer Risks for Carriers and Noncarriers From Families With a DNA Mismatch Repair Gene Mutation: A Prospective Cohort Study [Epidemiology] multi-national study

 Blogger's Note: some stats deleted for ease of reading, see abstract (or paid subscription for full details; interesting stat on female breast cancer


Colorectal and Other Cancer Risks for Carriers and Noncarriers From Families With a DNA Mismatch Repair Gene Mutation: A Prospective Cohort Study [Epidemiology]:

Purpose
To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population.

Patients and Methods
We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers.
Results
Over a median follow-up of 5 years, mutation carriers had an increased risk of

colorectal cancer (20.48),
endometrial cancer (30.62),  
ovarian cancer (18.81),
renal cancer (11.22),
pancreatic cancer ( 10.68), 
gastric cancer (9.78),  
urinary bladder cancer (9.51), and  
female breast cancer ( 3.95;).

We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (1.02).

Conclusion 
 We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.

abstract: Ventral hernia following primary laparotomy for ovarian, fallopian tube, and primary peritoneal cancers

An incisional hernia occurs in an area of weakness caused by an incompletely-healed surgical wound. Since median incisions in the abdomen are frequent for abdominal exploratory surgery, ventral incisional hernias are termed ventral hernias. ...
en.wikipedia.org/wiki/Ventral_hernia

OBJECTIVES: To evaluate the incidence and risk factors for ventral hernia development following primary laparotomy for ovarian, fallopian tube, and peritoneal cancers.
CONCLUSIONS: The development of ventral hernia is a significant postoperative morbidity in patients undergoing primary surgery for ovarian, tubal, or peritoneal cancer. Independent associations with hernia development include: BMI and IP chemotherapy by Year 1, and BMI, wound complications and advanced stage by Year 2.

Risk factors for non-invasive lesions of the fallopian tube in BRCA mutation carriers (study of 173 BRCA mutation carriers)

Objective

To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation.

Conclusion

The prevalence of tubal p53 signature and TIC (a tubal intra-epithelial carcinoma (TIC))  increases with age at salpingectomy and with BMI. Oral contraceptive use is associated with a decrease in the prevalence of TICs.

EvidenceUpdates - Bevacizumab (Avastin) increases risk for severe proteinuria in cancer patients including professional commentaries

article link:
http://plus.mcmaster.ca/EvidenceUpdates/NewArticles.aspx?Page=1&ArticleID=35795#Data

abstract link:
http://www.ncbi.nlm.nih.gov/pubmed/20538785?dopt=Abstract

abstract: A 67-Year-Old Woman with BRCA 1 Mutation Associated with Pancreatic Adenocarcinoma case report/discussion

Abstract

INTRODUCTION: There are approximately 40,000 new cases of pancreatic adenocarcinoma diagnosed in the USA each year. It is estimated that 5-10% of all patients with pancreatic cancer have a first-degree relative with the disease, while up to 20% of cases have a hereditary component. Individuals who carry a germline mutation in the BRCA 1 or 2 genes have an increased lifetime risk of developing pancreatic adenocarcinoma when compared with the general population.

CASE REPORT: Here, we present a case of metastatic pancreatic adenocarcinoma arising in a 67-year-old carrier of a BRCA 1 germline mutation.

DISCUSSION: In patients with known BRCA 1 or 2 mutation-associated pancreatic adenocarcinoma, the addition of a DNA cross-linking agent such as cisplatin, oxaliplatin, or mitomycin to a standard gemcitabine chemotherapy backbone should be considered. Poly ADP-ribose inhibitors are a novel class of drug, which have demonstrated promising efficacy in trials of BRCA 1 and 2 mutant breast and ovarian cancer, and are currently undergoing prospective evaluation in advanced pancreatic cancer.

Cardiovascular Safety of VEGF-Targeting Therapies: Current Evidence and Handling Strategies -- Girardi et al., 10.1634/theoncologist.2009-0235 -- The Oncologist

Abstract
Treatment with the angiogenesis inhibitors bevacizumab, sunitinib, and sorafenib as single agents or in combination with conventional chemotherapy is becoming a cornerstone of modern anticancer therapy. However, the potential toxicity of these drugs, mainly to the cardiovascular system, is still being investigated. Patient assessment at baseline, of crucial importance in candidates for treatment, involves the evaluation of risk factors and screening for past or present cardiovascular disease. Strict monitoring of treatment-related adverse effects must be conducted in order to allow the early detection of cardiovascular toxicities and their prompt medication. In the present paper, the most frequent cardiovascular toxicities and their underlying mechanisms are investigated, with a view to providing indications for effective patient management.

Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2 transcripts

BACKGROUND:
Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2.

CONCLUSIONS:
These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.

Attitudes Toward Information About Genetic Risk for Cognitive Impairment After Cancer Chemotherapy: Breast Cancer Survivors Compared With Healthy Controls

Conclusion
Results suggest lessened enthusiasm for genetic information that maintains or increases uncertainty about a specific course of action and highlight the importance of including clinically relevant groups in treatment decision-making research that employs hypothetical scenarios. Although women generally believe it is important to receive genetic information, they might benefit from assistance (eg, decision aid) in the difficult task of integrating information about survival and risk for adverse late effects from cancer treatment.

Genetic/Familial High-Risk Assessment: Breast and Ovarian — J Natl Compr Canc Network NCCN

Note: full free access; includes risks of Li-Fraumeni, Cowden and Lynch Syndromes

JCO -- Early Release CORRESPONDENCE Accrual Strategies for Cancer Genetics Research: Blurred Boundaries (ethics)

CORRESPONDENCE 
Accrual Strategies for Cancer Genetics Research: Blurred Boundaries

Daniel Rayson and Karen A. Gelmon JCO published online May 17, 2010, DOI:10.1200/JCO.2010.29.0759 [PDF]  

TO THE EDITOR: 

Metcalfe et al1 describe the incidence of BRCA1 and BRCA2 founder mutations in an unselected group of Ashkenazi Jewish women, with an astounding 2,000 women enrolled within 14 days of an article appearing in one of Canada’s most respected newspapers. Given the overwhelming interest amongthe target population, one might ask exactly what information prompted such an overwhelming response. The article in question was published on the front page of the Toronto Globe and Mail (Saturday May 24, 2008) with a large-font headline reading: “Cancer test a genetic crystal ball for Jewish women.” The first line in the piece stated: “For the first time in Canada, Jewish women will be offered the chance to alter their genetic destiny by taking a test…” a patently untrue and sensationalistic statement, given that presymptomatic BRCA1 and BRCA2 mutation testing, including Ashkenazi Jewish founder mutations, have been available for many years through medical genetics services nationwide." "The study by Metcalfe et al has accentuated these concerns and should serve as a basis for additional discussion in the oncology and
medical genetics communities regarding appropriate methodologies or recruitment to clinical investigations in cancer genetics."

Response to D. Rayson et al - re: Correspondence - Accrual strategies for cancer genetics research: blurred boundaries (ethics)

Correspondence: Narod/Metcalfe:

"If Drs Rayson and Gelmon1 are under the impression that we
have influence over how the Globe and Mail2 chooses to present its
news items, they are mistaken—perhaps their comments should be
addressed to the Globe Editorial office. We too are frustrated by the
incessant optimism of the media when they enter into the realms of
genetics or oncology—each gene discovery ineluctably will lead to a
treatment of a devastating genetic disease, each new molecule is a
target for a new cancer drug—but we suppose that unfettered optimism
is good for the newspaper business and is included in the price
we pay for freedom of the press...."

If the opinions of Drs Rayson and Gelmon are representative of the medical communities of Nova Scotia and British Columbia, then it is unlikely that populationbased genetic screening for Jewish women will be introduced in those provinces any time soon."

REFERENCES
1. Rayson D, Gelmon KA: Accrual strategies for cancer genetics research:
blurred boundaries. J Clin Oncol doi: 10.1200/JCO.2010.29.0759
2. Cancer test a genetic crystal ball for Jewish women. Toronto Globe and
Mail, Saturday May 24, 2008
3. Metcalfe KA, Poll A, Royer R, et al: Screening for founder mutations in
BRCA1 and BRCA2 in unselected Jewish women. J Clin Oncol 28:387-391, 2010
DOI: 10.1200/JCO.2010.29.1146; published online ahead of print at
www.jco.org on May 17, 2010

Teal Toes: Women’s Health Week, Ovarian Cancer media/video - link between breast/ovarian cancers

Note: no mention of other genetic risks aside from the BRCA's

abstract: The inherited genetics of ovarian and endometrial cancer

"Endometrial and epithelial ovarian cancers are the fourth and fifth most common cancers in women in developed countries, after breast, lung, and colorectal cancer. In the United States alone, in 2008 there were about 40000 new diagnoses of endometrial cancer and 7500 disease-related deaths. For ovarian cancer, there were about 22000 new diagnoses and 15000 deaths over the same period. The purpose of this article is to review the recent developments in the inherited genetics of ovarian and endometrial cancer, with particular attention to recent progress in identifying common low-penetrance susceptibility genes and their clinical implications."

full access: Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposit

Note: for full free access click on 'pdf'

What keeps you up at night? Genetics professionals' distressing experiences in patient care

Abstract 
PURPOSE:
 To explore specific patient care experiences that genetics professionals associate with distress and the emotions engendered by those experiences.
METHODS:: We conducted semistructured telephone interviews with clinical geneticists, genetic counselors, and genetic nurses that focused on a single distressing experience. RESULTS:: Fourteen clinical geneticists, 25 genetic counselors, and 14 nurses were interviewed. We categorized the situations that interviewees associated with distressing patient care experiences into seven major types: patient/family decisions (27% of total situations), giving bad news (17%), colleague behavior (15%), end-of-life issues (12%), unintended outcomes (12%), difficult patients (8%), and injustice/inhumanity (8%). Interviewees reported experiencing a variety of negative emotions during these situations, including anger, guilt, helplessness, and inadequacy.
CONCLUSIONS:: The distress and resulting emotions experienced by genetic service providers must be acknowledged. Interventions are needed to assist the clinician in becoming self-aware by reflecting on experienced emotions, examining belief systems and values, and understanding the connection between their emotions and behavior. Involvement in mindfulness meditation, reflective writing, peer support groups or additional communication skill-based training could address this need. In addition, clinicians should seek ways to increase personal meaning derived from providing patient care.

Myriad Loses Ruling Over Breast Cancer-Gene Patents (Update3) - BusinessWeek news article March 29, 2010

"The case is sure to be appealed to a court in Washington that specializes in patent law, and most likely to the Supreme Court.....

Years of Litigation:

He said today’s decision sets the stage for years of litigation to determine where the line is between what’s eligible for patents and what is not."

Breast cancer susceptibility variants alter risks in familial disease -- Latif et al. 47 (2): 126 -- Journal of Medical Genetics

"Conclusions:
This study confirms that susceptibility variants in FGFR2, TOX3 and MAP3K1 and on chromosome 8q are all associated with increased risk of cancer in individuals with a family history of breast cancer, whereas CASP8 is protective in this context. The level of risk is dependent on the strength of the family history and the presence of a BRCA1/2 mutation and contributes to the understanding of the use of these variants in clinical risk prediction."

JCO - Relationship Between Plasma Estradiol Levels and Estrogen-Responsive Gene Expression in Estrogen Receptor-Positive Breast Cancer in Postmenopausal Women UK/US study

Purpose To determine whether plasma estradiol (E2) levels are related to gene expression in estrogen receptor (ER)–positive breast cancers in postmenopausal women.

PLoS Genetics: Use of DNA–Damaging Agents and RNA Pooling to Assess Expression Profiles Associated with BRCA1 and BRCA2 Mutation Status in Familial Breast Cancer Patients

definition: heterogeneous - the quality of being diverse and not comparable in kind

full access:

"A large number of rare sequence variants of unknown clinical significance have been identified in the breast cancer susceptibility genes, BRCA1 and BRCA2. Laboratory
methods to identify which of these variants are mutations would have utility for counseling and clinical decision making when identified in patients with a family history of
breast cancer."

YouTube - Insidermedicine In Depth - February 8, 2010 - combination Paxil/Tamoxifen + clinical commentary