The Clinical Features of Ovarian Cancer in Hereditary Nonpolyposis Colorectal Cancer

Watson, Patrice; Bützow, Ralf; Lynch, Henry T.; Mecklin∥, Jukka–Pekka; Järvinen, Heikki; Vasen, Hans F. A.; Madlensky, Lisa; Fidalgo, Paulo; Bernstein, Inge

doi:10.1006/gyno.2001.6279

Cited by 215 publications

(150 citation statements)

References 28 publications

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“…OCPs decrease endometrial and ovarian cancer risks in the general population by approximately 50%, [34][35][36][37][38][39][40][41][42][43] and progestin intrauterine devices may reverse hyperplasia and early endometrial cancer. 44,45 Because Lynch syndrome-associated gynecologic cancers appear to be similar to sporadic cases, 4,46 these chemoprevention strategies may be beneficial with less adverse effect on quality of life than prophylactic surgery. Our group recently completed accrual to an endometrial cancer chemoprevention study comparing OCPs and Depo-Provera for women with Lynch syndrome, and data analysis currently is ongoing.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] These women also are at risk of developing ovarian cancer, with a lifetime risk of 10% to 12%. 4 Prophylactic hysterectomy with bilateral salpingo-oophorectomy (HBSO) after the completion of childbearing has been recommended as a prevention strategy. 5 Schmeler et al reported that prophylactic surgery prevented 100% of endometrial and ovarian cancers in this popula-tion.…”

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confidence: 99%

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Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

Kwon

Sun

Peterson

et al. 2008

Cancer

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BACKGROUND. Women with Lynch syndrome (hereditary nonpolyposis colorectal cancer) have an increased lifetime risk for endometrial and ovarian cancer. Screening and prophylactic surgery have been recommended as prevention strategies. In this study, the authors estimated the net health benefits and cost‐effectiveness of these strategies in a Markov decision‐analytic model. METHODS. Five strategies were compared for a hypothetical cohort of women with Lynch syndrome: 1) no prevention (‘reference’); 2) prophylactic surgery (hysterectomy and bilateral salpingo‐oophorectomy) at age 30 years; 3) prophylactic surgery at age 40 years; 4) annual screening with endometrial biopsy, transvaginal ultrasound, and CA 125 from age 30 years; and 5) annual screening from age 30 years until prophylactic surgery at age 40 years (combined strategy). Net health benefit was measured in quality‐adjusted life years (QALYs), and the primary outcome measured was the incremental cost‐effectiveness ratio (ICER). Baseline and transition probabilities were obtained from published literature, and costs were from the U.S. Department of Health and Human Services and Agency for Health Care Quality and Research. Sensitivity analyses were performed for uncertainty around various parameters. RESULTS. The combined strategy provided the highest net health benefit (18.98 QALYs) but had an ICER of $194,650 per QALY relative to the next best strategy (prophylactic surgery at age 40 years). Prophylactic surgery at age 30 years and annual screening were dominated by alternate strategies. CONCLUSIONS. Annual screening followed by prophylactic surgery at age 40 years was the most effective gynecologic cancer prevention strategy, but the incremental benefit over prophylactic surgery alone was attained at substantial cost. The ICER would become favorable by improving the effectiveness and reducing the costs of screening in this population. Cancer 2008. © 2008 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

Kwon

Sun

Peterson

et al. 2008

Cancer

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“…It is a common, autosomal dominant syndrome characterized by early onset (average age <45 years), and the occurrence of neoplastic lesions in a variety of tissues including endometrial, skin, ovarian, gastric, and renal. In the HNPCC population (up to 70 years of age), the cancer risks are 80% in colon, 20-60% in endometrium, 11-19% in stomach, and 9-11% in ovary, while, in the general population, the risks are 5.5% in colon, 2.7% in endometrium, <1% in stomach, and 1.6% in ovary (Kohlmann and Gruber, 2006;Watson et al, 2001). The diagnosis of HNPCC can be determined using the Amsterdam Criteria I, II (Vasen et al, 1999) and then by molecular genetic testing for germline mutations in mismatch repair genes.…”

Section: Mmr Defects and Human Cancermentioning

confidence: 99%

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Hsieh

Yamane

2008

Mechanisms of Ageing and Development

397

359

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DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.

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“…Genetic mutations in the MMR genes are frequently associated with either mucinous or endometrioid carcinoma [61,62] and also with synchronous endometrial and ovarian cancer.…”

Section: Ovarian Cancermentioning

confidence: 99%

“…The earlier development of breast cancer in affected individuals can also modify the risk of ovarian and other related cancers. A confirmed inherited BRCA mutation in a female is estimated to translate into a lifetime breast cancer risk of 70 -90%, higher if the family history is strong [62].…”

Section: Hereditary Breast and Ovarian Cancer Syndromementioning

confidence: 99%

Screening for gynaecologic cancers in genetically predisposed women

Dreyer

2012

Best Practice & Research Clinical Obstetrics & Gynaecol

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Hereditary breast and ovarian cancer (HBOC) syndrome and hereditary nonpolyposis colon cancer (HNPCC) syndrome are the two most important syndromes responsible for inherited cancers in gynaecology. Genetic testing is available for both these syndromes. BRCA testing is affordable and easy in patients with ancestry where the mutation patterns are known, other population groups need full gene screening. HNPCC can now be diagnosed more frequently with the use of immunohistochemistry.Ovarian cancer risk is high in HBOC syndromes and advanced screening techniques should be used when preventive surgery is not an option. Early detection techniques offer less protection than prophylactic removal, but enable the patient to retain her reproductive organs. Oophorectomy has the advantage of reducing breast cancer risk.In colorectal cancer syndromes the risk for endometrial and ovarian cancer is much elevated. These risks should be recognised and addressed as these diseases are easy to prevent.

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The Clinical Features of Ovarian Cancer in Hereditary Nonpolyposis Colorectal Cancer

Cited by 215 publications

References 28 publications

Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

DNA mismatch repair: Molecular mechanism, cancer, and ageing

Screening for gynaecologic cancers in genetically predisposed women

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