paywalled: Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers [Statistics in Oncology]

Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers [Statistics in Oncology]:

Purpose
To estimate the likely number and predictive strength of cancer-associated single nucleotide polymorphisms (SNPs) that are yet to be discovered for seven common cancers.

Methods
From the statistical power of published genome-wide association studies, we estimated the number of undetected susceptibility loci and the distribution of effect sizes for all cancers. Assuming a log-normal model for risks and multiplicative relative risks for SNPs, family history (FH), and known risk factors, we estimated the area under the receiver operating characteristic curve (AUC) and the proportion of patients with risks above risk thresholds for screening. From additional prevalence data, we estimated the positive predictive value and the ratio of non–patient cases to patient cases (false-positive ratio) for various risk thresholds.

Results
Age-specific discriminatory accuracy (AUC) for models including FH and foreseeable SNPs ranged from 0.575 for ovarian cancer to 0.694 for prostate cancer. The proportions of patients in the highest decile of population risk ranged from 16.2% for ovarian cancer to 29.4% for prostate cancer. The corresponding false-positive ratios were 241 for colorectal cancer, 610 for ovarian cancer, and 138 or 280 for breast cancer in women age 50 to 54 or 40 to 44 years, respectively.

Conclusion

Foreseeable common SNP discoveries may not permit identification of small subsets of patients that contain most cancers. Usefulness of screening could be diminished by many false positives. Additional strong risk factors are needed to improve risk discrimination.

abstract: BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : small study 14 Ashkenazi Jewish women

BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : Genetics in Medicine : Nature Publishing Group

Purpose:

BRCA genes are associated with hereditary breast and ovarian cancers. Guidelines worldwide currently recommend BRCA genetic testing in asymptomatic individuals only if they belong to “high-risk” families. However, population screening for BRCA1/2 may be the logical next step in populations with a high prevalence of founder mutations, such as Ashkenazi Jews. This study aimed to explore (i) the impact of a positive BRCA genetic test result on individuals who have neither a personal history nor a familial history of cancer and (ii) their attitudes toward the concept of population screening.

Methods:

Semistructured in-depth interviews were carried out with 14 Ashkenazi Jewish women who were asymptomatic BRCA carriers and who belonged to families with low prevalence of cancer.

Results:

Three main findings emerged: (i) having no family history of cancer was a source of optimism but also confusion; (ii) engaging in intensified medical surveillance and undergoing preventive procedures was perceived as health-promoting but also tended to induce a sense of physical and psychological vulnerability; and (iii) there was overall support for BRCA population screening, with some reservations.

Conclusion:

Women belonging to low-cancer-prevalence families within a “high-risk” ethnic community view BRCA genetic testing positively despite the difficulties entailed, because it allows prevention or early detection of cancer. However, implementing a BRCA population screening program should be carried out with proper pre- and post-testing preparation and support for the individuals undergoing testing.

Efficacy of an Educational Material on Second Primary Cancer Screening Practice for Cancer Survivors: A Randomized Controlled Trial

Efficacy of an Educational Material on Second Primary Cancer Screening Practice for Cancer Survivors: A Randomized Controlled Trial:

Conclusion
While the educational material was effective for increasing knowledge of SPC screening, it did not promote cancer screening practice among cancer survivors. More effective interventions are needed to increase SPC screening rates in this population.

Trial Registration
ClinicalTrial.gov NCT00948337

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.:

Study
Breast Cancer Res Treat. 2012 Mar 21;

Abstract

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations.

Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8 %. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77 % of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16 %).

Median age of onset for mutation carriers was 39 years. (?? Blogger's Note: screening guidelines...)  Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36 %) had a BRCA1 mutation, while 27 % of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48 % (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer.

It is noteworthy, however, that of the 65 carriers, 15 (23 %) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98 %). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.

Vignette-Based Study of Ovarian Cancer Screening: Do U.S. Physicians Report Adhering to Evidence-Based Recommendations?

Abstract

"Background: No professional society or group recommends routine ovarian cancer screening, yet physicians' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms.

Objective: To provide nationally representative estimates of physicians' reported nonadherence to recommendations against ovarian cancer screening.

Design: Cross-sectional survey of physicians offering women's primary care. The 12-page questionnaire contained a woman's annual examination vignette and questions about offers or orders for transvaginal ultrasonography (TVU) and cancer antigen 125 (CA-125).........."

Hereditary Cancer in Clinical Practice | Full text | Lynch syndrome: barriers to and facilitators of screening and disease management

Conclusions

Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.

Table 1. Participant characteristics

"Importantly, Lynch syndrome has significant implications for public health policy [4]. The ultimate plan should be to provide resources that enable individuals in high risk families to develop a strong sense of resilience and maintain a balanced screening schedule. In particular, this cohort requires timely and appropriate health care services, including:

○ A critical mass of genetic counselors to provide timely services to high risk families before, during and following genetic testing.

○ Service providers to coordinate and streamline diverse screening and treatment resources.

○ Health care providers, especially primary care physicians, informed about the risk of cancer within families and reinforcing the importance of maintaining recommended screening and initiating referrals to appropriate specialists.

○ Clinical monitoring tools designed to evaluate the impact of predictive testing and the ongoing psychosocial and behavioral adjustment to living in families with hereditary cancer. 

The current uncoordinated, physician dependent organization of screening for individuals with Lynch syndrome in Canada is inadequate. Given the incidence and prevalence of these hereditary cancers and the clinical benefits of screening, there is a critical need to provide integrated health care and timely follow-up in a manner that facilitates navigation of and access to the health system"

Vermillion plans to reduce headcount, expenses - financial news (OVA1)

Vermillion Inc. VRML -2.76% plans to reduce its headcount and other expenses and focus on strengthening sales of its ovarian cancer testing product (OVA1)  this year.

Effect of Screening on Ovarian Cancer Mortality, June 8, 2011 — JAMA

Gynecologic Oncology : Withdrawal from familial ovarian cancer screening for surgery: Findings from a psychological evaluation study (PsyFOCS)

Highlights

► Previous negative experiences of OC screening might lead women to opt for surgery.
► OC screening may be an interim risk management strategy before opting for surgery.

free full access paper + video: Effect of Screening on Ovarian Cancer Mortality, June 8, 2011 JAMA The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial

also:

JAMA Report Video This JAMA Report summarizes key findings from the article in video format and includes an interview with one of the authors.

The video script and links to the video are available at http://pubs.ama-assn.org/media/2011jer/0604.dtl#vnrscript

JAMA REPORT (VIDEO SCRIPT)

 

  VIDEO: Windows Media | Quicktime
   YEARLY OVARIAN CANCER SCREENING ASSOCIATED WITH NO REDUCTION IN DEATH AND INCREASED FALSE POSITIVE TESTS

New Cancer Screening Studies Offer Clarity, Room For Debate - WSJ.com

P\S\L - News: CA-125 Monitoring Fails to Make Decisions Easier for Treatment of Ovarian Cancer: Presented at NCCN

Q&A: Focus on Virtual Colonoscopy - Cancerwise | Cancer blog from MD Anderson Cancer Center

included comment:

What types of research is MD Anderson doing?

"Since bowel preparation is the largest barrier to most people seeking colon cancer screening, my research involves the development of new bowel cleansing approaches. These include solutions to dissolve feces and remove it from below without the need to drink the usual cleansing agents."

Biological diversity of ovarian cancer lessens value of screening

abstract: Breast and ovarian cancer screening of non-carriers from BRCA1/|2 mutation-positive families: 2-year follow-up of cohorts from France and Quebec : European Journal of Human Genetics

free full access - Cancer screening in the United States, 2011 - CA: A Cancer Journal for Clinicians - Wiley Online Library

Cancer Screening in the United States, 2011

A Review of Current American Cancer Society Guidelines and Issues in
Cancer Screening

HealthLinx Releases Initial Results from First Stage of 1,150-Subject OvPlex Study | ProteoMonitor | Proteomics | GenomeWeb

Ultrasound for Ovarian Cancer Screening: Are We Throwing the Baby out with the Bath Water? abstract

Questions remain for more aggressive ovarian cancer screening | HemOncToday

How well can a screening test predict disease risk? « Genomes Unzipped