Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2019; 10(11): 358-368
Published online Nov 24, 2019. doi: 10.5306/wjco.v10.i11.358
Germline mutations in Thai patients with nonmucinous epithelial ovarian cancer
Tarinee Manchana, Prasit Phowthongkum, Chinachote Teerapakpinyo
Tarinee Manchana, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
Prasit Phowthongkum, Division of Medical Genetics, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Medical Genetics Center, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
Chinachote Teerapakpinyo, Chulalongkorn GenePRO Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Author contributions: Manchana T designed the research study, collected and analyzed the data and wrote the paper; Phowthongkum P provided genetic counseling, interpreted the genetic database and wrote the paper; Teerapakpinyo C performed germline mutation analysis and interpreted the genetic database.
Institutional review board statement: Institutional Review Board, Faculty of Medicine, Chulalongkorn University.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Tarinee Manchana, MD, Associate Professor, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, 1873, Rama IV Road, Patumwan, Bangkok 10330, Thailand. tarinee.m@chula.ac.th
Telephone: +66-2-2564000 (ext. 2114) Fax: +66-2-2527376
Received: March 2, 2019
Peer-review started: March 4, 2019
First decision: April 11, 2019
Revised: August 13, 2019
Accepted: November 4, 2019
Article in press: November 4, 2019
Published online: November 24, 2019
Abstract
BACKGROUND

Genetic testing is widely recommended for all epithelial ovarian cancer (EOC) patients. However, an increased probability of identifying germline mutations has been reported in selected patients with risk factors such as a family history or personal history of cancer and high-grade serous carcinoma (HGSC) subtype. HGSC has been reported to be the most common subtype of EOC worldwide (approximately 70%). However, this subtype is less prevalent in Thai patients (reported as only 20%). The difference in the distribution of various subtypes of EOC may reflect the incidence of germline mutations in Thai EOC patients.

AIM

To evaluate the frequencies of germline mutations in EOC patients and to compare the frequencies in those with and without clinical risk factors for hereditary ovarian cancer.

METHODS

This cross-sectional study included 112 nonmucinous EOC patients who underwent primary surgery at our tertiary care hospital. Clinical risk factors for hereditary ovarian cancer were defined as follows: Age below 40 years, a significant family history of cancer, synchronous ovarian and endometrial cancer, and HGSC. Comprehensive germline mutations were detected by next-generation sequencing.

RESULTS

Of a total of 112 patients, 82 (73.2%) patients had ≥ 1 risk factor and 30 (26.8%) patients had no risk factors. Germline mutations were detected in 26 patients: 20 (17.8%) patients had BRCA1/2 mutations, but 6 (5.4%) patients had mutations in other genes, including 1 in MLH1, 1 in MSH2, 1 in RAD51C, 2 in ATM and 1 in CDH1. Germline mutations were only detected in patients with risk factors (26 of 82, 31.7%), not in patients without risk factors (P < 0.001). A significant family history of cancer and HGSC were the only two significant risk factors associated with a higher proportion of germline mutations (56.3% vs 10% for those with and without a history of cancer, respectively, 40.8% vs 9.5% for those with and without HGSC). Germline BRCA mutations were detected in 38.8% of patients with HGSC but in only 1.6% of those with non-HGSC. An age below 40 years, personal history of breast cancer, and synchronous ovarian and endometrial cancer were not significant factors (14.3% vs 23.5%, 33.3% vs 21%, 22.2% vs 22.3%).

CONCLUSION

Approximately one-third of EOC patients with risk factors had germline mutations. Almost all germline BRCA mutations were found in patients with the HGSC subtype. Selected patients with HGSC and a family history of cancer should be initially considered for genetic analysis in Thailand.

Keywords: BRCA mutation, Epithelial ovarian cancer, Germline mutation, Thai

Core tip: Germline mutations could not be detected in any epithelial ovarian cancer patients without risk factors such as age below 40 years, significant family or personal history of cancer, and high-grade serous subtype. Mutations were detected in approximately one-third of patients with these risk factors: 25% had BRCA1/2 mutations, 5% had mutations in other homologous recombination genes, and 2.5% had MMR mutations. Significantly more germline mutations were found in patients with a family history of cancer, especially ovarian cancer. Germline BRCA mutations were detected in 38.8% of patients with the high-grade serous subtype but in only 1.6% of those with a non-high-grade serous subtype. Selected patients with the high-grade serous subtype or a significant family history of cancer should initially be considered for genetic analysis in limited resource settings.