Impact of genetic testing on endometrial cancer risk-reducing practices in women at risk for Lynch syndrome

Dana-Farber Cancer Institute, Boston, MA, USA
Gynecologic Oncology (Impact Factor: 3.69). 08/2012; 127(3). DOI: 10.1016/j.ygyno.2012.08.031
Source: PubMed

ABSTRACT OBJECTIVE: Due to the increased lifetime risk of endometrial cancer (EC), guidelines recommend that women with Lynch syndrome (LS) age≥35 undergo annual EC surveillance or prophylactic hysterectomy (PH). The aim of this study was to examine the uptake of these risk-reducing strategies. METHODS: The study population included women meeting clinical criteria for genetic evaluation for LS. Data on cancer risk-reducing behaviors were collected from subjects enrolled in two distinct studies: (1) a multicenter cross-sectional study involving completion of a one-time questionnaire, or (2) a single-center longitudinal study in which subjects completed questionnaires before and after undergoing genetic testing. The main outcome was uptake of EC risk-reducing practices. RESULTS: In the cross-sectional cohort, 58/77 (75%) women at risk for LS-associated EC reported engaging in EC risk-reduction. Personal history of genetic testing was associated with uptake of EC surveillance or PH (OR 17.1; 95% CI 4.1-70.9). Prior to genetic testing for LS, 26/40 (65%) women in the longitudinal cohort reported engaging in EC risk-reduction. At one-year follow-up, 16/16 (100%) mismatch repair (MMR) gene mutation carriers were adherent to guidelines for EC risk-reduction, 9 (56%) of whom had undergone PH. By three-year follow-up, 11/16 (69%) MMR mutation carriers had undergone PH. Among women with negative or uninformative genetic test results, none underwent PH after testing. CONCLUSIONS: Genetic testing for LS is strongly associated with uptake of EC risk-reducing practices. Women found to have LS in this study underwent prophylactic gynecologic surgery at rates comparable to those published for BRCA1/2 mutation carriers.

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    ABSTRACT: Riskreducing surgery (RRS) is defined as a prophylactic approach with removal of organs at high risk of developing cancer, which is performed in cases without lesions or absence of clinically significant lesions. Hereditary gynecological cancers for which RRS is performed include hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. For HBOC, RRS in the United States (US) is recommended for women with mutations in the breast cancer susceptibility (BRCA)1 and BRCA2 genes and bilateral salpingooophorectomy (BSO) is generally performed. This procedure may reduce the risk of breast, ovarian, Fallopian tube and primary peritoneal cancer, although ovarian deficiency symptoms occur postoperatively. For Lynch syndrome, RRS in the US is considered for postmenopausal women or for women who do not desire to bear children and BSO and hysterectomy are usually performed. This approach may reduce the risk of endometrial and ovarian cancer, although ovarian deficiency symptoms also occur. For RRS, there are several issues that must be addressed to reduce the risk of cancer development in patients with HBOC or Lynch syndrome. To the best of our knowledge, this is the first review to discuss RRS with a focus on hereditary gynecological cancer.
    Molecular and Clinical Oncology 03/2015; 3(2). DOI:10.3892/mco.2014.460
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    ABSTRACT: We have recently experienced an endometrial cancer 12 years after the diagnosis of colon cancer with Lynch syndrome. A 49-year-old Korean woman had a family history of colon cancer. Her mother had colon cancer at 56-year-old, and her brother had colon cancer at 48 years old. The patient received surgery for endometrial cancer at the same hospital 12 years after being treated for colon cancer. Immunohistochemistry showed that her endometrial tissue stained negative for MSH2. A microsatellite instability test was performed and showed the presence of instability high microsatellite instability. An hMLH2 gene mutation was detected at codon 629 codon of exon 12, in which a glutamine was replaced with an arginine (1886A>G [p.Gln629Arg]). To our knowledge, this is the first case of metachronous cancer in a Lynch syndrome family in Korea with a gap of more than ten years between cancer diagnoses.
    11/2013; 56(6):408-11. DOI:10.5468/ogs.2013.56.6.408
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    ABSTRACT: Lynch syndrome is the most common cause of hereditary colon cancer, and accounts for as much as 3% of all colon and endometrial cancers. The identification and management of individuals with Lynch syndrome have evolved over the past 20 years, yet the syndrome remains vastly underdiagnosed. It is important for clinicians to recognize individuals and families who are at risk in order to be able to manage them appropriately and reduce their morbidity and mortality from this condition. This review will touch on the history of Lynch syndrome, the current knowledge of genotype–phenotype correlations, the cancers associated with Lynch syndrome, and management of individuals who are gene carriers.
    The Application of Clinical Genetics 07/2014; 2014(7):147-158. DOI:10.2147/TACG.S51483


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May 21, 2014