Germline mutations in Thai patients with nonmucinous epithelial ovarian cancer

Table 1 Patient characteristics of patients with and without clinical risk factors

Characteristics	Patients with risk factors (n = 82)	Patients without risk factor (n = 30)	P value
Mean age (yr)	51.8 ± 11.7	55.6 ± 8.3	0.06
Menopause, n (%)	39 (47.6)	17 (56.7)	0.52
Diagnosis, n (%)
Epithelial ovarian cancer	67 (81.7)	30 (100)	0.10
Fallopian tube cancer	4 (4.9	0
Peritoneal cancer	2 (2.4)	0
Synchronous ovarian and endometrial cancer	9 (11.0)	0
Histologic subtype, n (%)
High-grade serous	49 (59.8)	0	< 0.001
Low-grade serous	4 (4.9)	2 (6.7)
Endometrioid	15 (18.3)	13 (43.3)
Clear cell	12 (14.6)	12 (40.0)
Mixed endometrioid and clear cell	1 (1.2)	3 (10.0)
Adenocarcinoma	1 (1.2)	0
Stage, n (%)
1	27 (32.9)	13 (43.3)	0.06
2	10 (12.2)	8 (26.7)
3	38 (46.3)	9 (30.0)
4	7 (8.5)	0
Platinum sensitivity, n (%)	66 (80.5)	23 (76.7)	0.73
Germline mutation, n (%)	26 (31.7)	0	< 0.001

Table 2 Details of epithelial ovarian cancer patients with germline mutations

Age (yr)	Gene	Mutation			Variant classification	Cancer	Family history of cancer	Synchro-nous cancers	Histology
		Nucleotide change	Protein change	Type
63	BRCA1	c.1889delA	p.Asn630IlefsTer2	Frameshift	Pathogenic	Ovarian cancer IIIC	Ovarian cancer (sister)	-	High-grade serous
64	BRCA1	c.981_982delAT	p.Cys328Ter	Frameshift	Pathogenic	Ovarian cancer IIIB	Ovarian cancer (sister)	-	High-grade serous
56	BRCA1	c.5072C>A	p.Thr1691Lys	Missense	Likely pathogenic	Fallopian tube cancer IIA	-	-	High-grade serous
52	BRCA1	c.3748G>T	p.Glu1250Ter	Nonsense	Pathogenic	Peritoneal cancer IIIC	Breast cancer (mother) ovarian cancer (sister)	-	High-grade serous
46	BRCA1	c.2059C>T	p.Gln687Ter	Nonsense	Pathogenic	Ovarian cancer IIIC	Ovarian cancer (grandmother)	-	High-grade serous
72	BRCA1	c.3049G>T	p.Glu1017Ter	Nonsense	Pathogenic	Ovarian cancer IIIA	Breast cancer (2 sisters) endometrial cancer (mother)	-	High-grade serous
57	BRCA1	c.3770_3771delAG	p.Glu1257GlyfsTer9	Frameshift	Pathogenic	Ovarian cancer IIIC	Breast cancer (aunt)	-	High-grade serous
51	BRCA1	c.1426delC	p.His476MetfsTer2	Frameshift	Pathogenic	Ovarian cancer IVB	Breast cancer (niece)	-	High-grade serous
35	BRCA1	c.3020C>A	p.Ser1007Ter	Nonsense	Pathogenic	Ovarian cancer IIIC	Breast cancer (mother)	-	High-grade serous
63	BRCA1	c.3181delA	p.Ile1061Ter	Frameshift	Pathogenic	Tubal cancer IVB	-	-	High-grade serous
69	BRCA1	c.1155G>A	p.Trp385Ter	Nonsense	Pathogenic	Tubal cancer IC	-	-	High-grade serous
45	BRCA1	c.3049G>T	p.Glu1017Ter	Nonsense	Pathogenic	Ovarian cancer IVB	-	-	High-grade serous
62	BRCA1	c.4327C>T	p.Arg1443	Frameshift	Pathogenic	Peritoneal cancer IIB	Breast cancer (daughter) Breast and ovarian cancer (sister) endometrial cancer (sister)	-	High-grade serous
59	BRCA1	c.981_982delAT	p.Cys328Ter	Frameshift	Pathogenic	Ovarian cancer IIIC	Breast cancer (sister)	-	High-grade serous
49	BRCA2	c.4126G > T	p.Gly1376Ter	Nonsense	Pathogenic	Ovarian cancer IIIC	Breast cancer (sister) Prostate cancer (uncle) Colon cancer (uncle)	-	High-grade serous
56	BRCA2	c.7558C > T	p.Arg2520Ter	Nonsense	Pathogenic	Ovarian cancer IIIC	-	-	High-grade serous
60	BRCA2	c.3109C > T	p.Gln1037Ter	Nonsense	Pathogenic	Ovarian cancer IVB	Breast cancer (2 sisters)	Breast cancer	High-grade serous
49	BRCA2	c.1367_1368delAG	p.Lys457GlufsTer4	Frameshift	Pathogenic	Ovarian cancer IIIC	Ovarian cancer (mother)	Breast cancer	High-grade serous
40	BRCA2	c.22_23delAG	p.Arg8AlafsTer4	Frameshift	Pathogenic	Ovarian cancer IIIC	Breast cancer (sister)	-	Clear cell carcinoma
63	BRCA2	c.1405_1406delGA	p.Asp469	Nonsense	Pathogenic	Ovarian cancer IIB	-	Breast cancer	High-grade serous
46	MLH1	c.109G > A	p.Glu37Lys	Nonsense	Likely pathogenic	Ovarian cancer IIC and endometrial cancer IAG1	Colon cancer (grandfather, father and uncle)	-	Well differentiated serous and well differentiated endometrioid
48	MSH2	c.1183C > T	p.Gln395Ter	Nonsense	Pathogenic	Ovarian cancer IA and endometrial cancer IAG1	Endometrial cancer (aunt)	Endometrial cancer	Endometrioid
48	CDH1	c.1118C > T	p.Pro373Leu	Missense	Likely pathogenic	Ovarian cancer IC and endometrial cancer IAG3	-	Endometrial cancer	Endometrioid with clear cell
54	RAD51C	c.905-2A > C	Not applicable	Splice site loss	Likely pathogenic	Ovarian cancer IIIC	Ovarian cancer (mother)	-	High-grade serous
67	ATM	c.1402_1403delAA	p.Lys468GlufsTer18	Frameshift	Likely pathogenic	Ovarian cancer IA	-	Breast cancer (Triple- negative)	Clear cell
52	ATM	c.8431_8432delAA	p.Lys2811ValfsTer3	Frameshift	Likely pathogenic	Ovarian cancer IIIC	Colon cancer (mother, aunt) liver cancer (aunt)	-	Clear cell

Table 3 Frequency of germline mutations according to various clinical risk factors

Risk factors	Number of patients	BRCA1, n (%)	BRCA2, n (%)	Other genes, n (%)
None	30	0	0	0
Family history of cancers (breast/ovary/endometrium/colon)	32	10 (31.2)	4 (12.5)	4 (12.5) (1ATM, 1RAD51C,1 MLH1, 1MSH2)
Family history of breast cancer	22	6 (27.3)	3 (13.6)	0
Family history of ovarian cancer	10	5 (50.0)	1 (10.0)	1 (10.0) (RAD51C)
Personal history of breast cancer	12	0	3 (25.0)	1 (8.3) (ATM)
Two primary ovarian and endometrial cancer	9	0	0	3 (33.3) (1 MLH1, 1MSH2, 1CDH1)
High-grade serous carcinoma	49	14 (28.6)	5 (10.4)	1 (2.1) (RAD51C)
Young age (< 40 yr)	14	1 (7.1)	1 (7.1)	0