Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome

Engel, Christoph; Loeffler, Markus; Steinke, Verena; Rahner, Nils; Holinski‐Feder, Elke; Dietmaier, Wolfgang; Schackert, Hans K.; Goergens, Heike; Doeberitz, Magnus von Knebel; Goecke, Timm O.; Schmiegel, Wolff; Buettner, Reinhard; Möeslein, Gabriela; Letteboer, Tom G.W.; Gómez-García, Encarna B.; Hes, Frederik J.; Hoogerbrugge, Nicoline; Menko, Fred H.; Os, Theo A.M. van; Sijmons, Rolf H.; Wagner, Anja; Kluijt, Irma; Propping, Peter; Vasen, Hans F. A.

doi:10.1200/jco.2012.43.2278

Cited by 269 publications

(238 citation statements)

References 29 publications

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“…The cumulative risk at age 70 was 9.1% (95% CI: 4.4-13.8). 8 The two patients who provided prostate tumor tissue for testing had mixed results, with the prostate tumor from patient 4 (deletion of exons 1-6 in MSH2) exhibiting both loss of protein expression and MSI, whereas the prostate tumor from patient 6 (deletion of exon 8 in MSH2) had intact protein expression and microsatellite stability. We conclude that although impaired MMR function may contribute to prostate cancer development in some cases, it is unlikely to do so in all cases.…”

Section: Discussionmentioning

confidence: 99%

“…4 Prostate and breast cancer are currently not considered part of the LS tumor spectrum. Some studies have revealed an increased incidence of prostate cancer, especially in patients carrying an MSH2 mutation, [5][6][7][8] whereas others have not shown an increased incidence. 2,9,10 Two studies have shown a lack of MMR protein expression in prostate cancer tumors in patients with LS.…”

Section: Introductionmentioning

confidence: 99%

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Prostate cancer incidence in males with Lynch syndrome.

Haraldsdóttir¹,

Hampel²,

Wei³

et al. 2013

JCO

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Purpose-An increased risk of prostate cancer is currently not considered a part of the Lynch syndrome spectrum. The purpose of this study was to retrospectively examine prostate cancer incidence in the Lynch syndrome cohort at the Ohio State University in comparison with that in the general population.Methods-We included all males diagnosed with Lynch syndrome from June 1998 to June 2012 at the Ohio State University and obtained baseline information including cancer history. If patients had not been seen in the 12 months before June 2012, they were contacted to document changes in their cancer history. We compared prostate cancer incidence among the Lynch syndrome families with that of the general population by using the Surveillance, Epidemiology, and End Results registry 1999-2009.Results-Of the 188 males identified with Lynch syndrome, 11 males were diagnosed with prostate cancer during the study period. The ratio of observed to expected numbers of prostate cancer cases resulted in a standardized rate ratio of 4.87 (95% confidence interval: 2.43-8.71). Impaired mismatch repair expression and microsatellite instability were seen in one out of two prostate cancer specimens available for testing. Conclusion-Maleswith Lynch syndrome had a nearly fivefold increased risk of developing prostate cancer but did not appear to have earlier onset or a more aggressive phenotype.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prostate cancer incidence in males with Lynch syndrome.

Haraldsdóttir¹,

Hampel²,

Wei³

et al. 2013

JCO

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“…The syndrome is characterized by inheritance of a germline mutation in genes of the DNA mismatch repair system, namely, MLH1, PMS2, MSH2, or MSH6, which are mutated in differing frequencies (26)(27)(28). Patients with Lynch syndrome-associated ovarian cancer have a mean age at presentation of 48 years (compared with a median age of ~68 years in those without Lynch syndrome), with approximately 50% of patients having stage I cancer.…”

Section: [H2] Risk Factorsmentioning

confidence: 99%

Ovarian cancer

Matulonis

Sood

Fallowfield

et al. 2016

Nat Rev Dis Primers

898

787

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Ovarian cancer is not a single disease and can be subdivided into at least five different 2 histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at late stage, and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents, and poly (ADP ribose) polymerase (PARP) inhibitors are used and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and is typically very responsive to platinum-based chemotherapy at diagnosis. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy.Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Significant progress has been made in identifying genes associated with high risk of ovarian cancer (such as BRCA1 and BRCA2) as well as a precursor lesion of HGSC called a serous tubal intraepithelial carcinoma, which hold promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. Competing interestsU.A.M. has served as a consultant for AstraZeneca, ImmunoGen, Pfizer, Genentech, and Merck.

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“…23 Individuals with Lynch syndrome also are predisposed to other cancers, such as urothelial cancers, small bowel cancer in men, and breast cancer in women. 24 For individuals identified as HNPCC mutation carriers, annual/biennial colorectal screening with colonoscopy is recommended from age 20 years, and yearly gynecologic examination with transvaginal ultrasound is recommended for women starting at age 30 years. 25 If they have an adenomatous polyposis coli (APC) gene mutation, then individuals with FAP have a nearly 100% risk of colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Psychiatric implications of cancer genetic testing

Hirschberg

Chan‐Smutko

Pirl

2014

Cancer

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As genetic testing for hereditary cancer syndromes has transitioned from research to clinical settings, research regarding its accompanying psychosocial effects has grown. Men and women being tested for hereditary cancer syndromes may experience some psychological distress while going through the process of testing or after carrier status is identified. Psychological distress appears to decrease over the course of the first year and it is typically not clinically significant. Longer term studies show mixed results with some mutation carriers continuing to experience elevated distress. Baseline distress is the greatest risk factor for both immediate (weeks-12 months) and long-term psychological distress (18 mo-8 years post genetic testing). In addition to baseline psychological distress, other risk factors can be identified to help identify individuals who may need psychosocial interventions during the genetic testing process. The challenges of providing clinical care to the growing population of individuals identified to be at increased risk for heritable cancers present opportunities for research and new models of care. Cancer 2015;121:341-60. V C 2014 American Cancer Society.KEYWORDS: BRCA1, BRCA2, HNPCC, Lynch syndrome, genetic testing, unaffected carrier, carrier, hereditary cancer syndrome, riskreducing surgeries, psychosocial. INTRODUCTIONSeveral familial cancer syndromes that confer a high lifetime risk of cancer can be identified with genetic testing, and greater numbers of men and women will consider testing as the availability and public awareness of genetic testing for cancer susceptibility continue to increase. Research to date suggests that these individuals will have varied emotional responses to the process of genetic testing as well as its results.When genetic testing for cancer syndromes first transitioned from research protocols to clinics, there was initial concern that it would be similar to genetic testing for Huntington disease. Many worried that knowing they are at high risk for cancer in the future may be too distressing for some individuals, possibly even leading to suicide. However, several systematic reviews focusing primarily on hereditary breast and ovarian cancer (HBOC) and Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC), have demonstrated that most individuals who have a mutation identified in an associated gene cope well with the knowledge of their genetic status. 1-3 Data regarding psychological implications of the genetic testing process are the most robust for women who present for HBOC risk assessment, which involves discussion of the BRCA1 and BRCA2 genes, although there are increasing studies for HNPCC, familial adenomatous polyposis (FAP), and other hereditary cancer syndromes.Although the rates of distress in individuals undergoing genetic testing vary, they appear to be relatively small. Studies have demonstrated that approximately 6% to 24% of individuals undergoing genetic testing for a BRCA1/BRCA2-associated or HNPCC-associated mutations repo...

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Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome

Cited by 269 publications

References 29 publications

Prostate cancer incidence in males with Lynch syndrome.

Prostate cancer incidence in males with Lynch syndrome.

Ovarian cancer

Psychiatric implications of cancer genetic testing

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