New Genetic Clues to Breast Cancer? - Drugs.com MedNews

SUNDAY Jan. 22, 2012 --
"Researchers have identified three new genomic regions they believe are linked with breast cancer that may help explain why some women develop the disease..........Scientists conducting genome-wide association studies -- research that looks at the association between genetic factors and disease to pinpoint possible causes -- had already identified 22 breast cancer susceptibility loci. Locus is the physical location of a gene or DNA sequence on a chromosome. "The three [newly identified] loci take the number of common susceptibility loci from 22 to 25," said Easton. However, the three new susceptibility loci might explain only about 0.7 percent of the familial risks of breast cancer, bringing the total contribution to about 9 percent, the researchers said.'".......

abstract: DICER1 Mutations in Familial Multinodular Goiter (thyroid) With and Without Ovarian Sertoli-Leydig Cell Tumors

define: 

multinodular goiter - A multinodular goiter is  a thyroid gland that is usually enlarged and contains multiple thyroid nodules.

Pleuropulmonary blastoma (PPB) is a rare cancer originating in the lung or pleural cavity....
en.wikipedia.org/wiki/Pleuropulmonary_blastoma

 

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Objective To determine whether familial MNG  (multinodular goiter) with or without SLCT (Sertoli-Leydig cell tumor of the ovary) in the absence of PPB (pleuropulmonary blastoma)  was associated with mutations in DICER1. 

 

Conclusions DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.

News - Penn State Biochemistry and Molecular Biology Colorectal Cancer month/Lynch Syndrome excerpt

"Lynch syndrome, previously referred to as hereditary non-polyposis colorectal cancer or HNPCC, represents the most common hereditary cause of colorectal cancer.
Approximately 1 in 400 to 1 in 500 individuals in the general population are estimated to have Lynch syndrome.

Knowledge, as they say, in this condition, is power. Not only should individuals with Lynch syndrome start their colonoscopies earlier (at 20-25 years of age) and have them more frequently (every 1-2 years), they should also be screened for stomach and small intestine cancer, urinary tract cancers involving the kidneys and ureters, and the hepatobiliary tract, including the gallbladder, bile duct, pancreas and liver.

Further, women with Lynch syndrome should be aware of the increased risk for both endometrial and ovarian cancer and offered the option of prophylactic surgery following childbearing."

March 2011: Hereditary Cancer in Clinical Practice | Full text | Lynch Syndrome - is breast cancer a feature?

Background

The debate on whether or not breast cancer is in the tumor spectrum for Lynch syndrome produces a conundrum for healthcare providers.

The classic tumor spectrum for Lynch Syndrome (LS) includes colon, endometrial, ovarian, stomach, small intestine, hepatobiliary, urinary tract and brain/central nervous system cancers. Muir-Torre Syndrome (MTS) is a variant of LS that is associated with additional skin lesions including sebaceous gland tumors and keratoacanthomas. MTS was observed in 28% of LS families when assessing for MTS skin lesions [1]. It has also been reported that 10-14% of individuals with MTS present initially with breast cancer [2,3]. An extensive study published in 2002 excluded breast cancer as part of the tumor spectrum associated with LS [4].

However, more recently it was reported that DNA mismatch repair (MMR) gene deficiencies were identified in 51% of breast cancers arising in MMR mutation carriers [5]. Another study reported a male with an MLH1 mutation who had both colon and breast cancer. The breast cancer exhibited somatic reduction to homozygosity for the MLH1 mutation [6].

Here we report two unrelated families in which the proband has a germline MMR gene mutation and bilateral breast cancer, and one family in which the proband had ovarian and renal cancer and her daughter, maternal aunt and cousin had breast cancer at age 47, 59, and 48 respectively.

This raises the question are these breast cancers associated with the MMR mutations or a breast cancer susceptibility gene and what testing should be offered?

Conclusion

Our findings indicate that breast cancer is part of the spectrum of tumors in LS families in which the breast cancer segregates with the other LS associated tumors.

Additional hereditary breast cancer gene testing may not be warranted in these circumstances. A future research goal is to perform IHC on the breast tumors from these families to determine if they show loss of expression of the MMR gene that is known to be altered.

....cont'd (full free access)

abstract + Free Full-Text (2010) Familial Pancreatic Cancer (includes discussion regarding BRCA/Lynch Syndrome/FAMMM and others)

Abstract: Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.
Keywords: phenotypic and genotypic heterogeneity; high mortality; genetic counseling; biomarker paucity; FAMMM syndrome; Li-Fraumeni syndrome; Lynch syndrome; pancreatic cancer

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.

full access: Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics-multi-national study

 Introduction

Familial non-syndromic colorectal cancer (CRC) constitutes one of the most difficult and diverse patient groups encountered in a genetics clinic, with no apparent germline mutation, an often-indeterminant mode of inheritance, and questions arising as to how to manage the probands, and how to identify which family members are also at risk for CRC........ The clinical significance of HPS is that it is associated with an increased personal and familial risk of CRC , and extra-colonic cancers in the wider family setting .

 Conclusion

A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

Future Medicine - Women's Health - re: EVA trial (full free access to commentary/abstract of original paper) MRI high risk familial risk breast cancer

link: 

Screening of women at high familial risk of breast cancer

Steven A Narod
 
Evaluation of:  Kuhl C, Weigel S, Schrading S et al.: Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J. Clin. Oncol. 28, 1450–1457 (2010).

"In the EVA trial, Kuhl et al. screened 687 women at high risk of breast cancer for up to 3 years with annual MRI. A total of 27 breast cancers were diagnosed, including 11 DCIS and two local recurrences. There were no interval cancers. This data suggests that MRI screening can be used to downstage breast cancers, but larger studies with longer follow-up periods are required to confirm these findings."

The original paper-link to abstract:
Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial

*note comments: Study to Evaluate Families with History of Carcinoid Cancer

Note:  this study is an NIH study and excludes those with a known genetic syndrome

Study to Evaluate Families with History of Carcinoid Cancer
By The Carcinoid Cancer Foundation (CCF)

The Natural History of Familial Carcinoid Tumor is recruiting participants who are interested in being part of a study that will “evaluate families with a history of carcinoid cancer to determine ways to improve early detection and to find the gene that may cause the tumors.”

If you are a member of a family in which two or more immediate blood relatives have had gastrointestinal carcinoid tumors, you may be eligible for this study. Unaffected spouses of family members diagnosed with carcinoid cancer are also requested to participate.

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

GeneCards: List of Disease Genes

Note: genes/disease relevance/links to further information

examples:

BRCA2 breast cancer 2, early onset 13q12.3

* Breast-ovarian cancer, familial, 2
* Fanconi anemia, complementation group D1
* Prostate cancer
* Breast cancer, male, susceptibility to
* Wilms tumor
* Medulloblastoma
* Glioblastoma
* Pre-B-cell acute lymphoblastic leukemia
* Pancreatic cancer

MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) 2p22-p21

* Colorectal cancer, hereditary nonpolyposis, type 1
* Muir-Torre syndrome
* Mismatch repair cancer syndrome

Familial relative risks for breast cancer by pathological subtype: a population-based cohort study