Identification of women at risk for hereditary breast and ovarian cancer in a sample of 1000 Slovenian women: a comparison of guidelines.

BACKGROUND: An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines. METHODS: Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored. RESULTS: NCCN guidelines identify 13.2% of women, ACMG/NSGC guidelines identify 7.1% of women, and SGO guidelines identify 7.0% of women from the Slovenian population, while 6.2% of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer. CONCLUSIONS: We identified 13.7% of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying nearly twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.

Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer's disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called "nutraceuticals" epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.

Genetic Interactions in Nonsyndromic Orofacial Clefts in Europe-EUROCRAN Study.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL±P) and nonsyndromic cleft palate (nsCP) are caused by a combination of genetic and environmental risk factors. We investigated gene-environment and gene-gene joint effects in a large multicenter study of case-parent triads. METHODS: The nsCL±P or nsCP triads were recruited in 11 European countries between 2001 and 2005. We collected DNA samples from infants and from their mothers and fathers, and mothers completed a questionnaire on exposures, including smoking and folic acid supplement use during pregnancy. We used log-linear regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between nsCL±P or nsCP and variants in MTHFR, MTHFD1, TGFA, SATB2, and MSX1, stratifying by environmental or genetic factors. RESULTS: We obtained genotype and exposure data for 728 nsCL±P triads and 292 nsCP triads. In male infants, there was no association between the mother's homozygous MSX1 p(CA) *4/*4 genotype and nsCL±P (RR, 0.98; 95% CI, 0.63-1.54), but this maternal genotype resulted in a doubling of risk for female infants (RR, 2.21; 95% CI, 1.13-4.34). There was evidence suggestive of gene-gene joint-effects between MTHFR-TGFA for nsCP but not for nsCL±P. CONCLUSION: Although we chose the genes and their variants and putative joint effects based on associations previously reported in the literature, we replicated few associations. These results do not provide evidence supporting associations between these genes and oral clefts in European populations, although gene-environment and gene-gene interactions could play a role in oral cleft etiology.