Germline breast cancer susceptibility genes, tumor characteristics, and survival

Ho, Peh Joo; Khng, Alexis J.; Loh, Hui Wen; Ho, Weang-Kee; Yip, Cheng Har; Mohd-Taib, Nur Aishah; Tan, Veronique Kiak Mien; Tan, Benita Kiat-Tee; Tan, Su-Ming; Tan, Ern Yu; Lim, Swee Ho; Jamaris, Suniza; Sim, Yirong; Wong, Fuh Yong; Ngeow, Joanne; Lim, Elaine Hsuen; Tai, Mei Chee; Wijaya, Eldarina Azfar; Lee, Soo Chin; Chan, Ching Wan; Buhari, Shaik Ahmad; Chan, Patrick M. Y.; Chen, Juliana J. C.; Seah, Jaime Chin Mui; Lee, Wai Peng; Mok, Chi Wei; Lim, Geok Hoon; Woo, Evan; Kim, Sung-Won; Lee, Jong Won; Lee, Min Hyuk; Park, Sue K.; Dunning, Alison M.; Easton, Douglas F.; Schmidt, Marjanka K.; Teo, Soo-Hwang; Li, Jingmei; Hartman, Mikael

doi:10.1186/s13073-021-00978-9

Table 2 Associations between protein-truncating variant [PTV] carriership (34 genes) and demographics, and tumor characteristics

From: Germline breast cancer susceptibility genes, tumor characteristics, and survival

	(i) PTV 34 genes				(ii) PTV 34 genes—excluding BRCA1/2 carriers
	Non-carrier	Carrier	OR (*95% CI*)	p	Non-carrier	Carrier	OR (*95% CI*)	p
*Demographics*
Family history
No	6437	531	1.00 (reference)		6437	346	1.00 (reference)
Yes	1061	159	1.89 (1.56 to 2.29)	<0.001	1061	81	1.43 (1.12 to 1.84)	0.005
Unknown	375	289	2.08 (1.27 to 3.41)	0.004	375	30	1.26 (0.61 to 2.58)	0.531
Age group (adjusted for ethnicity and study)
≥50	4453	389	1.00 (reference)		4453	245	1.00 (reference)
<50	3394	586	1.36 (1.17 to 1.58)	<0.001	3394	209	1.09 (0.90 to 1.32)	0.384
Missing age	26	4	2.61 (0.84 to 8.06)	0.096	26	3	3.23 (0.88 to 11.83)	0.077
Ethnicity (adjusted for age at diagnosis only)
Chinese (MyBrCa)	2361	227	1.00 (reference)		2361	142	1.00 (reference)
Chinese (SGBCC)	3390	287	0.91 (0.76 to 1.10)	0.341	3390	202	1.01 (0.81 to 1.26)	0.955
Malay (MyBrCa)	556	63	1.07 (0.79 to 1.44)	0.676	556	25	0.71 (0.45 to 1.10)	0.124
Malay (SGBCC)	542	52	1.00 (0.73 to 1.37)	0.989	542	31	0.95 (0.64 to 1.42)	0.818
Indian (MyBrCa)	404	48	1.25 (0.90 to 1.74)	0.185	404	26	1.08 (0.70 to 1.66)	0.729
Indian (SGBCC)	238	17	0.78 (0.47 to 1.30)	0.338	238	4	0.28 (0.10 to 0.78)	0.014
Korean	282	280	8.38 (6.68 to 10.50)	<0.001	282	24	1.28 (0.80 to 2.04)	0.308
Others/unknown	100	5	0.51 (0.18 to 1.39)	0.187	100	3	0.40 (0.10 to 1.63)	0.199
*Tumor characteristics*
Stage
0	703	56	0.83 (0.60 to 1.14)	0.247	703	34	0.96 (0.64 to 1.43)	0.822
I	2038	206	1.00 (reference)		2038	103	1.00 (reference)
II	2421	325	1.34 (1.10 to 1.63)	0.003	2421	161	1.33 (1.03 to 1.72)	0.028
III	1007	116	1.29 (1.00 to 1.66)	0.047	1007	61	1.23 (0.89 to 1.70)	0.216
IV	240	30	1.49 (0.98 to 2.26)	0.064	240	11	0.96 (0.50 to 1.81)	0.889
Unknown	1464	246	1.30 (1.05 to 1.61)	0.015	1464	87	1.14 (0.85 to 1.54)	0.379
Cumulative logistic model	6409	733	*1.32 (1.14 to 1.52)*	*<0.001*	6409	370	1.18 (0.98 to 1.42)	0.090
Tumor behavior
In situ	949	79	1.00 (reference)		949	43	1.00 (reference)
Invasive	6628	850	1.48 (1.15 to 1.91)	0.003	6628	401	1.35 (0.97 to 1.87)	0.073
Unknown	296	50	1.13 (0.74 to 1.72)	0.583	296	13	0.74 (0.36 to 1.50)	0.401
Nodal status
Negative	4282	483	1.00 (reference)		4282	240	1.00 (reference)
Positive	2519	370	1.28 (1.10 to 1.49)	0.002	2519	168	1.20 (0.98 to 1.47)	0.081
Unknown	1072	126	0.89 (0.71 to 1.11)	0.290	1072	49	0.78 (0.56 to 1.07)	0.127
Grade
Well-differentiated	947	82	1.00 (reference)		947	58	1.00 (reference)
Moderately differentiated	2980	304	1.23 (0.94 to 1.61)	0.131	2980	154	0.85 (0.62 to 1.16)	0.311
Poorly differentiated	2672	366	1.64 (1.26 to 2.14)	<0.001	2672	177	1.09 (0.80 to 1.48)	0.577
Unknown	1274	227	1.25 (0.94 to 1.68)	0.124	1274	68	0.81 (0.56 to 1.18)	0.272
Cumulative logistic model	6599	752	*1.41 (1.21 to 1.64)*	*<0.001*	6599	389	1.16 (0.95 to 1.41)	0.140
Tumor size, cm
≤2	1019	152	1.00 (reference)		1019	41	1.00 (reference)
2–5	1599	238	1.39 (1.09 to 1.77)	0.007	1599	119	1.92 (1.33 to 2.77)	<0.001
>5	3582	334	1.47 (1.11 to 1.93)	0.007	3582	205	1.48 (0.98 to 2.23)	0.060
Unknown	1673	255	1.36 (1.06 to 1.74)	0.014	1673	92	1.38 (0.93 to 2.05)	0.108
Cumulative logistic model	6200	724	*1.24 (1.02 to 1.50)*	*0.030*	6200	365	1.20 (0.92 to 1.55)	0.177
Estrogen receptor status
Positive	5034	508	1.00 (reference)		5034	283	1.00 (reference)
Negative	1933	309	1.40 (1.19 to 1.64)	<0.001	1933	121	1.11 (0.89 to 1.38)	0.368
Unknown	906	162	1.20 (0.97 to 1.49)	0.092	906	53	0.96 (0.70 to 1.31)	0.786
Progesterone receptor status
Positive	4296	426	1.00 (reference)		4296	232	1.00 (reference)
Negative	2461	359	1.40 (1.20 to 1.64)	<0.001	2461	149	1.13 (0.91 to 1.40)	0.257
Unknown	1116	194	1.33 (1.09 to 1.62)	0.005	1116	76	1.20 (0.91 to 1.57)	0.200
HER2 receptor status
Positive	1735	159	1.00 (reference)		1735	108	1.00 (reference)
Negative	4061	584	1.42 (1.17 to 1.73)	<0.001	4061	235	0.93 (0.73 to 1.18)	0.537
Unknown	2077	236	1.12 (0.90 to 1.40)	0.302	2077	114	0.85 (0.65 to 1.12)	0.254
Proxy subtype
Luminal A	2244	204	1.00 (reference)		2244	113	1.00 (reference)
Luminal B [HER2−]	729	108	1.68 (1.30 to 2.18)	<0.001	729	52	1.46 (1.04 to 2.05)	0.029
Luminal B [HER2+]	947	86	0.97 (0.74 to 1.27)	0.823	947	59	1.24 (0.90 to 1.72)	0.196
HER2-overexpressed	705	52	0.83 (0.60 to 1.15)	0.272	705	36	1.02 (0.69 to 1.50)	0.912
Triple-negative	727	187	2.22 (1.76 to 2.80)	<0.001	727	51	1.38 (0.98 to 1.95)	0.065
Unknown	2521	342	1.20 (0.98 to 1.45)	0.072	2521	146	1.12 (0.86 to 1.44)	0.400

Models are adjusted for age at diagnosis (years) and the joint variable of study and ethnicity. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multinomial logistic regression models with each tumor characteristic as the outcome and genetic factors as explanatory variables; patients with unknown values were excluded from the analysis. p-value from Wald test. Results associated with p < 0.05 are denoted in bold

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