Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer

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3 Citations (Scopus)

Abstract

Objective: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. Methods: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Results: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. Conclusion: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.

Original languageEnglish
Article numbere29
JournalJournal of Gynecologic Oncology
Volume29
Issue number3
DOIs
Publication statusPublished - 2018 May 1

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Hereditary Nonpolyposis Colorectal Neoplasms
Ovarian Neoplasms
DNA Mismatch Repair
Methylation
Mutation
Microsatellite Instability
Germ-Line Mutation
Genetic Testing
Population
Genes
Immunohistochemistry
Guidelines
Costs and Cost Analysis
Neoplasms

Keywords

  • Lynch syndrome
  • Medical history taking
  • Mismatch repair
  • Ovarian neoplasms
  • Risk assessments
  • Society of gynecologic oncology

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

@article{5499f4da86074bb0a242e89a162ffda9,
title = "Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer",
abstract = "Objective: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4{\%} of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. Methods: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Results: Of the 129 cases, 25 (19.4{\%}) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0{\%} (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. Conclusion: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.",
keywords = "Lynch syndrome, Medical history taking, Mismatch repair, Ovarian neoplasms, Risk assessments, Society of gynecologic oncology",
author = "Takashi Takeda and Kosuke Tsuji and Kouji Banno and Megumi Yanokura and Yusuke Kobayashi and Eiichirou Tominaga and Daisuke Aoki",
year = "2018",
month = "5",
day = "1",
doi = "10.3802/jgo.2018.29.e29",
language = "English",
volume = "29",
journal = "Journal of Gynecologic Oncology",
issn = "2005-0380",
publisher = "Korean Society of Gynecologic Oncology and Colposcopy",
number = "3",

}

TY - JOUR

T1 - Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer

AU - Takeda, Takashi

AU - Tsuji, Kosuke

AU - Banno, Kouji

AU - Yanokura, Megumi

AU - Kobayashi, Yusuke

AU - Tominaga, Eiichirou

AU - Aoki, Daisuke

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Objective: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. Methods: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Results: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. Conclusion: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.

AB - Objective: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. Methods: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Results: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. Conclusion: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.

KW - Lynch syndrome

KW - Medical history taking

KW - Mismatch repair

KW - Ovarian neoplasms

KW - Risk assessments

KW - Society of gynecologic oncology

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JO - Journal of Gynecologic Oncology

JF - Journal of Gynecologic Oncology

SN - 2005-0380

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