Published online Nov 24, 2019. doi: 10.5306/wjco.v10.i11.358
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
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.
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.
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.
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%).
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.
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.