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Table 3 Associations between protein-truncating variant [PTV] carriership (9 and 25 genes) and tumor characteristics

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

 

(i) 9 genes

(ii) 9 genes—excluding BRCA1/2 carriers

(iii) 25 genes

 

Non-carrier

Carrier

OR (95% CI)

p

Non-carrier

Carrier

OR (95% CI)

p

Non-carrier

Carrier

OR (95% CI)

p

Stage

 0

727

32

0.75 (0.49 to 1.14)

0.182

727

10

0.99 (0.48 to 2.05)

0.987

703

24

0.94 (0.58 to 1.50)

0.79

 I

2111

133

1.00 (reference)

 

2111

30

1.00 (reference)

 

2038

73

1.00 (reference)

 

 II

2516

230

1.48 (1.17 to 1.88)

0.001

2516

66

1.86 (1.20 to 2.87)

0.006

2421

95

1.11 (0.81 to 1.52)

0.504

 III

1047

76

1.36 (1.00 to 1.86)

0.051

1047

21

1.41 (0.80 to 2.49)

0.23

1007

40

1.15 (0.78 to 1.71)

0.478

 IV

248

22

1.85 (1.13 to 3.02)

0.015

248

3

0.89 (0.27 to 2.93)

0.844

240

8

0.98 (0.47 to 2.07)

0.961

 Missing

1513

197

1.54 (1.19 to 1.98)

<0.001

1513

38

1.74 (1.06 to 2.84)

0.028

1464

49

0.91 (0.62 to 1.32)

0.61

 Cumulative logistic model

6649

493

1.43 (1.20 to 1.70)

<0.001

6649

130

1.29 (0.95 to 1.75)

0.108

6409

192

1.03 (0.79 to 1.33)

0.83

Tumor behavior

 In situ

979

49

1.00 (reference)

 

979

13

1.00 (reference)

 

949

30

1.00 (reference)

 

 Invasive

6878

600

1.64 (1.19 to 2.26)

0.003

6878

151

1.62 (0.91 to 2.88)

0.102

6628

250

1.22 (0.83 to 1.81)

0.309

 Missing

305

41

1.30 (0.79 to 2.12)

0.302

305

4

0.50 (0.11 to 2.26)

0.37

296

9

0.84 (0.38 to 1.86)

0.662

Nodal status

 Negative

4438

327

1.00 (reference)

 

4438

84

1.00 (reference)

 

4282

156

1.00 (reference)

 

 Positive

2623

266

1.34 (1.12 to 1.61)

0.002

2623

64

1.28 (0.92 to 1.79)

0.139

2519

104

1.15 (0.89 to 1.49)

0.283

 Missing

1101

97

0.97 (0.75 to 1.27)

0.848

1101

20

0.89 (0.53 to 1.48)

0.643

1072

29

0.72 (0.48 to 1.09)

0.121

Grade

 Well-differentiated

997

32

1.00 (reference)

 

997

8

1.00 (reference)

 

947

50

1.00 (reference)

 

 Moderately differentiated

3080

204

2.33 (1.56 to 3.49)

<0.001

3080

54

2.15 (1.02 to 4.54)

0.045

2980

100

0.65 (0.46 to 0.92)

0.015

 Poorly differentiated

2767

271

3.48 (2.35 to 5.17)

<0.001

2767

82

3.67 (1.77 to 7.62)

<0.001

2672

95

0.69 (0.48 to 0.97)

0.036

 Missing

1318

183

2.42 (1.60 to 3.66)

<0.001

1318

24

2.05 (0.90 to 4.65)

0.087

1274

44

0.62 (0.41 to 0.95)

0.028

 Cumulative logistic model

6844

507

1.88 (1.56 to 2.26)

<0.001

6844

144

2.04 (1.48 to 2.82)

<0.001

6599

193

0.89 (0.68 to 1.17)

0.411

Tumor size, cm

 ≤2

1047

124

1.00 (reference)

 

1047

13

1.00 (reference)

 

1019

28

1.00 (reference)

 

 2–5

1677

160

1.19 (0.90 to 1.56)

0.229

1677

41

2.03 (1.08 to 3.81)

0.028

1599

78

1.84 (1.18 to 2.86)

0.007

 >5

3712

204

1.57 (1.14 to 2.17)

0.006

3712

75

2.03 (1.02 to 4.04)

0.044

3582

130

1.23 (0.75 to 2.04)

0.415

 Missing

1726

202

1.44 (1.10 to 1.90)

0.009

1726

39

2.02 (1.04 to 3.90)

0.037

1673

53

1.10 (0.68 to 1.80)

0.693

 Cumulative logistic model

6436

488

1.34 (1.07 to 1.69)

0.012

6436

129

1.54 (1.00 to 2.37)

0.05

6200

187

1.11 (0.78 to 1.58)

0.55

Estrogen receptor status

5218

324

1.00 (reference)

 

5218

99

1.00 (reference)

     

 Positive

2003

239

1.66 (1.37 to 2.00)

<0.001

2003

51

1.34 (0.95 to 1.89)

0.095

5034

184

1.00 (reference)

 

 Negative

941

127

1.34 (1.04 to 1.72)

0.021

941

18

0.92 (0.54 to 1.58)

0.773

1933

70

0.98 (0.74 to 1.30)

0.908

 Missing

        

906

35

0.97 (0.67 to 1.42)

0.895

Progesterone receptor status

 Positive

4448

274

1.00 (reference)

 

4448

80

1.00 (reference)

 

4296

152

1.00 (reference)

 

 Negative

2548

272

1.64 (1.36 to 1.98)

<0.001

2548

62

1.35 (0.96 to 1.89)

0.08

2461

87

1.01 (0.77 to 1.33)

0.924

 Missing

1166

144

1.40 (1.11 to 1.78)

0.005

1166

26

1.16 (0.73 to 1.84)

0.535

1116

50

1.21 (0.87 to 1.68)

0.26

HER2 receptor status

 Positive

1812

82

1.00 (reference)

 

1812

31

1.00 (reference)

 

1735

77

1.00 (reference)

 

 Negative

4203

442

2.12 (1.64 to 2.73)

<0.001

4203

93

1.30 (0.86 to 1.96)

0.211

4061

142

0.78 (0.59 to 1.04)

0.093

 Missing

2147

166

1.56 (1.17 to 2.08)

0.002

2147

44

1.18 (0.74 to 1.90)

0.486

2077

70

0.73 (0.52 to 1.02)

0.061

Proxy subtype

 Luminal A

2320

128

1.00 (reference)

 

2320

37

1.00 (reference)

 

2244

76

1.00 (reference)

 

 Luminal B [HER2−]

753

84

2.15 (1.58 to 2.92)

<0.001

753

28

2.37 (1.44 to 3.91)

<0.001

729

24

1.01 (0.63 to 1.61)

0.981

 Luminal B [HER2+]

989

44

0.75 (0.52 to 1.09)

0.133

989

17

1.08 (0.61 to 1.93)

0.789

947

42

1.31 (0.89 to 1.92)

0.175

 HER2-overexpressed

732

25

0.63 (0.40 to 0.99)

0.046

732

9

0.77 (0.37 to 1.60)

0.483

705

27

1.15 (0.73 to 1.80)

0.548

 Triple-negative

755

159

2.85 (2.17 to 3.73)

<0.001

755

23

1.90 (1.12 to 3.23)

0.018

727

28

1.13 (0.72 to 1.76)

0.601

 Unknown

2613

250

1.30 (1.02 to 1.64)

0.033

2613

54

1.27 (0.83 to 1.95)

0.27

2521

92

1.04 (0.76 to 1.42)

0.804

  1. All models are adjusted for study, ethnicity, and age at diagnosis. 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. PTV9 genes includes ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53. PTV25 genes includes ABRAXIS1, AKT1, BABAM2, BRIP1, CDH1, EPCAM, FANCC, FANCM, GEN1, MEN1, MRE11A, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PIK3CA, PMS2, PTEN, RAD50, RECQL, RINT1, SKT11, and XRCC2. p-value from Wald test. Test for trend of stage, grade, and tumor size was done using the cumulative logistic model, excluding patients with missing values. Results associated with p < 0.05 are denoted in bold
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