abstract: Surveillance for hereditary cancer: Does the benefit outweigh the psychological burden?—A systematic review

Surveillance for hereditary cancer: Does the benefit outweigh the psychological burden?—A systematic review


Individuals at risk for developing hereditary cancer are offered surveillance in order to improve the prognosis. An important question is whether the benefit of surveillance outweighs the psychological burden. In this review, we evaluated all studies that investigated psychological distress and the quality of life in individuals under surveillance for hereditary cancer of the breast, ovarian, prostate, pancreas, colorectum, melanoma, and various rare syndromes such as familial adenomatous polyposis, Li–Fraumeni and Peutz–Jeghers syndrome.Thirty-two studies were identified. Surveillance for most hereditary cancers was associated with good psychological outcomes. However, surveillance of individuals at high risk for developing multiple tumors appeared to be associated with increased distress and a lower quality of life. Common factors associated with worse psychological outcomes included a personal history of cancer, female gender, having a first degree relative with cancer, negative illness perceptions and coping style. The use of a simple screening tool to identify distressed individuals is recommended.

abstract: Familial Risks in Cancer of Unknown Primary: Tracking the Primary Sites

Conclusion:

The present data show that CUP is not a disease of random metastatic cancers but, instead, a disease of a defined set of cancers. The association of CUP with families of kidney, lung, and colorectal cancers suggests a marked genetic basis and shared metastatic mechanisms by many cancer types. Familial sites shared by CUP generally match those arising in tissue-of-origin determinations and, hence, suggest sites of origin for CUP. Mechanistic exploration of CUP may provide insight into defense against primary tumors and the metastatic process.

Women's Health - Full Text: Preventing familial breast and ovarian cancer: major research advances with little implication

Preventing familial breast and ovarian cancer: major research advances with little implication

Primary prevention of hereditary breast–ovarian cancer syndrome, which accounts for 5–10% of all breast cancer diagnosis, represents a prime paradigm of excellence of personalized medicine [1,2]. However, genetic testing can reveal that BRCA mutation carriers account for less than 25% of the familial risk. There has been little progress in explaining the missing heritability of the remaining 75% of women with family history who test negative for BRCA mutations. Neither recently identified common low-penetrance variants alone, nor their interactions with established environmental risk factors, are able to explain missing heritability. But even among BRCA mutation carriers, the decision by an expert scientific team for the optimal preventive strategy, choosing between prophylactic surgery and intensive surveillance, is very difficult and should be individualized for each woman. Here we discuss the latest advances in breast cancer genetics, their potential to impact prevention strategies and practices, and the future perspectives for a true personalized preventive medicine...........

Missing heritability	ChooseTop of pageRare BRCA mutationsMissing heritability <<Genome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Previous work has suggested the polygenic model to help understand the 75% of breast cancer familial risk [6]. According to this model, the missing heritability could be explained by the accumulation of low to moderate genetic risk variants other than BRCA1/2 genes, namely BRCA3 or BRCA4 high-penetrance genes. Indeed, more than 15 years after the discovery of BRCA1/2 genes, the ‘classical’ linkage studies in high-risk families have identified no other high-penetrance genes. The completion of the HapMap 3 project with a database of common and rare variants [7] and high-throughput screening technology has allowed a new generation of association studies to provide improved understanding of the genetics of familial cancer.

Rare BRCA mutations	ChooseTop of pageRare BRCA mutations <<Missing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Missing heritability	ChooseTop of pageRare BRCA mutationsMissing heritability <<Genome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Genome-wide association studies	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s... <<Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Next generation of GWAS	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWAS <<Whole-genome ...Current practical prevent...ConclusionBiliography

Whole-genome & exome sequencing	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ... <<Current practical prevent...ConclusionBiliography

Current practical preventive approaches	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent... <<ConclusionBiliography

Conclusion	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...Conclusion <<Biliography

abstract: Familial Risks in Cancer of Unknown Primary: Tracking the Primary Sites — JCO

free full access: Familial colorectal cancer risk: ESMO Clinical Practice Guidelines — Ann Oncol

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Lynch syndrome

prevalence and penetrance of mismatch-repair gene mutations

Lynch syndrome is the most common hereditary colorectal cancer (CRC) syndrome and it accounts for ∼1%–3% of all CRC burden. The syndrome is transmitted with an autosomal dominant pattern and it is associated with mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2. These alterations lead to tumour DNA instability at microsatellites (MSI) and foster inactivating mutations in tumour suppressors containing microsatellites (i.e. TGF-βRII and BAX). Mutations in the MMR genes may lead to loss of expression of the corresponding protein and be detected by immunohistochemistry (IHC) techniques.

Overall, mutation carriers mainly have an increased risk of CRC (lifetime 30%–70%) and endometrial cancer (lifetime 30%–60%). Other extracolonic tumours observed at increased risk (lifetime 5%–15%) are urinary tract, small intestine, ovary, gastric, pancreas, biliary tract, brain and sebaceous gland tumours. A genotype–phenotype correlation has been observed in which MLH1 mutation carriers are at higher risk of young onset CRC cancer, MSH2 at higher risk of extracolonic cancers, MSH6 at increased risk of endometrial cancer and PMS2 carriers show a lower lifetime absolute risk of CRC and endometrial cancer (15%–20%) compared with other mutation carriers.

The name Turcot syndrome refers to patients with MMR gene mutations and brain tumours, and the name Muir–Torre syndrome to patients with cutaneous gland tumours (keratoacanthomas, sebaceous adenomas or adenocarcinomas)......cont'd

Candidate gene association studies: successes and failures

Abstract

"Epidemiologic studies of twins indicate that 20-40% of common tumors such as breast, colorectal, and prostate cancers are inherited. However, the effect of high penetrance tumor susceptibility genes such as APC, BRCA1, BRAC2, MSH1, MLH2 and MSH6 only accounts for a small fraction of these cancers. Low to moderate penetrance tumor susceptibility genes likely account for the large remaining proportion of familial cancer risk...."