March 6, 2012 - Screening for Colorectal Cancer: A Guidance Statement From the American College of Physicians (pdf) including high risk

Blogger's Note: if searching for Lynch Syndrome, the older term 'HNPCC' will need to be used


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"Genetic or clinical diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC): colonoscopy every one to two years beginning at age 20 to 25 years or 10 years before the age of the youngest case in the immediate family."

abstract: Informed consent to microsatellite instability and immunohistochemistry screening for Lynch syndrome (ethics/informed consent)

From the 1Department of Bioethics, Cleveland Clinic; 2Genomic Medicine Institute Lerner College of Medicine, Cleveland Clinic; and 3Center for Genomic Research Ethics & Law, Case Western Reserve University, Cleveland, Ohio.

Abstract

OBJECTIVE: Routine microsatellite instability (MSI) and immunohistochemistry (IHC) screening of colorectal cancers can assist in identifying a significant proportion of cancers attributable to Lynch syndrome. This article considers whether it is necessary to obtain patient informed consent for microsatellite instability and immunohistochemistry screening.

RESULTS: Although microsatellite instability screening examines genetic features of a tumor, it lacks several important characteristics that typically mandate formal informed consent to genetic testing. Microsatellite instability screening describes discrete tissue samples and does not provide information about the rest of the patient's body or germline. In contrast, immunohistochemistry screening is a proteomic test that may reveal information about the patient's germline. As such, immunohistochemistry screening can be viewed as similar to other forms of genetic testing, in which explicit patient consent is regarded as an ethical prerequisite.

CONCLUSION: There is no ethical requirement to obtain explicit informed consent for microsatellite instability screening of colorectal tumor samples for Lynch syndrome. There is support for obtaining patient consent to immunohistochemistry testing, given its similarities with other genetic analyses for which informed consent is typically deemed necessary. Regardless of which screening test is used, it is important to prepare patients and their families for the possibility of a positive screening test.

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)