Huntington disease (HD) prevalence shows geographic variability and has been recently updated by taking in account the mutation diagnostic test. In Italy, the last epidemiological estimation was reported well before the HTT gene discovery and the availability of the corresponding genetic test. It reported a prevalence of affected subjects ranging between 2.3 to 4.8/100,000 in some restricted areas of Northern Italy. We have performed a service-based epidemiological analysis in a very restricted geographic area named Molise, where our institutions currently operate and represent the only point of reference for rare neuropsychiatric diseases. The estimated prevalence found was of 10.85/100,000 (95% CI: 7.20-14.50), remarkably higher than that previously described before the gene test analysis was available, and expected to increase of an additional 17% by 2030, due to Italian population aging. According to our analysis, we estimate that about 6,000 subjects are currently affected by HD in Italy, and that this number will further increase in the next decades due to population aging, variable phenotype penetrance and improved life expectancy.

KEYWORDS:

Huntington disease; Italy; epidemiology; prevalence

PMID:: 25689972; [PubMed - as supplied by publisher]

Disclosing Genetic Risk for Coronary Heart Disease: Effects on Perc... - PubMed - NCBI

2015 Feb 23. doi: 10.1111/cge.12577. [Epub ahead of print]

Disclosing Genetic Risk for Coronary Heart Disease: Effects on Perceived Personal Control and Genetic Counseling Satisfaction.

Robinson CL1, Jouni H, Kruisselbrink TM, Austin EE, Christensen KD, Green RC, Kullo IJ.

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Abstract

We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 40-65 years) were randomized to receive estimated 10-y-risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs. 24.1 ± 3.8, P=0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs. 15.9 ± 6.3, P=0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (P=NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation.

KEYWORDS:

clinical genetics; clinical trial; coronary heart disease; genetic counseling; genetic risk score; perceived personal control

PMID:: 25708169; [PubMed - as supplied by publisher]

Genomic Classifier Identifies Men With Adverse Pathology After Radi... - PubMed - NCBI

2015 Feb 9. pii: JCO.2014.59.0026. [Epub ahead of print]

Genomic Classifier Identifies Men With Adverse Pathology After Radical Prostatectomy Who Benefit From Adjuvant Radiation Therapy.

Den RB1, Yousefi K2, Trabulsi EJ2, Abdollah F2, Choeurng V2, Feng FY2, Dicker AP2, Lallas CD2, Gomella LG2, Davicioni E2, Karnes RJ2.

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Abstract

PURPOSE:

The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making.

PATIENTS AND METHODS:

GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis.

RESULTS:

The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01).

CONCLUSION:

In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.

PMID:: 25667284; [PubMed - as supplied by publisher]

A Modified Lynch Syndrome Screening Algorithm in Colon Cancer: BRAF... - PubMed - NCBI

2015 Mar;143(3):336-43. doi: 10.1309/AJCP4D7RXOBHLKGJ.

A Modified Lynch Syndrome Screening Algorithm in Colon Cancer: BRAF Immunohistochemistry Is Efficacious and Cost Beneficial.

Roth RM1, Hampel H2, Arnold CA3, Yearsley MM3, Marsh WL3, Frankel WL3.

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Abstract

OBJECTIVES:

Somatic BRAF mutation in colon cancer essentially excludes Lynch syndrome. We compared BRAF V600E immunohistochemistry (IHC) with BRAF mutation in core, biopsy, and whole-section slides to determine whether IHC is similar and to assess the cost-benefit of IHC.

METHODS:

Resection cases (2009-2013) with absent MLH1 and PMS2 and prior BRAF mutation polymerase chain reaction results were chosen (n = 57). To mimic biopsy specimens, tissue microarrays (TMAs) were constructed. In addition, available biopsies performed prior to the resection were available in 15 cases. BRAF V600E IHC was performed and graded on TMAs, available biopsy specimens, and whole-section slides. Mutation status was compared with IHC, and cost-benefit analysis was performed.

RESULTS:

BRAF V600E IHC was similar in TMAs, biopsy specimens, and whole-section slides, with only four (7%) showing discordance between IHC and mutation status. Using BRAF V600E IHC in our Lynch syndrome screening algorithm, we found a 10% cost savings compared with mutational analysis.

CONCLUSIONS:

BRAF V600E IHC was concordant between TMAs, biopsy specimens, and whole-section slides, suggesting biopsy specimens are as useful as whole sections. IHC remained cost beneficial compared with mutational analysis, even though more patients needed additional molecular testing to exclude Lynch syndrome.