TABLE 21

Hazard ratios from the Cox model for age at the development of breast cancer in BRCA2 carriers, by overall breast cancer risk score (split into quintiles)

Overall breast cancer risk scoreCategoryMedian age (years) at the development of breast cancer (95% CI)HR95% CIp-valueHarrell’s C
18 SNPsaQuintile 1 (highest risk)43.31 (39.67 to 49.64)1.001.00p < 0.0010.59
Quintile 246.78 (43.65 to 48.11)0.970.68 to 1.38
Quintile 349.66 (45.26 to 53.79)0.660.46 to 0.95
Quintile 449.37 (46.22 to 57.08)0.630.44 to 0.91
Quintile 5 (lowest risk)52.46 (49.1 to 58.60)0.470.33 to 0.69
9 SNPsbQuintile 1 (highest risk)45.16 (42.23 to 49.26)1.001.00p < 0.0010.58
Quintile 246.55 (42.53 to 48.93)1.010.71 to 1.45
Quintile 346.24 (44.16 to 48.92)0.940.67 to 1.33
Quintile 453.87 (48.11 to 60.90)0.510.35 to 0.75
Quintile 5 (lowest risk)53.79 (50.11 to 58.6)0.490.33 to 0.71
5 SNPscQuintile 1 (highest risk)46.27 (42.78 to 49.65)1.001.00p < 0.0010.57
Quintile 246.67 (41.28 to 49.64)1.000.70 to 1.42
Quintile 346.78 (42.88 to 48.93)1.010.71 to 1.43
Quintile 452.36 (49.11 to 58.51)0.560.38 to 0.81
Quintile 5 (lowest risk)52.08 (46.28 to 59.06)0.570.38 to 0.84
15 SNPsdQuintile 1 (highest risk)45.16 (41.28 to 49.26)1.001.00p < 0.0010.59
Quintile 245.26 (42.78 to 47.16)1.050.74 to 1.49
Quintile 348.19 (44.3 to 51.99)0.750.52 to 1.07
Quintile 453.79 (48.78 to 59.06)0.520.36 to 0.75
Quintile 5 (lowest risk)54.53 (49.11 to 58.51)0.480.33 to 0.70

HR, hazard ratio.

a

Validated in a general population. ORs and RAFs taken from Turnbull et al.131

b

Validated in BRCA2 mutation carriers. ORs and RAFs taken from Antoniou et al.136,137

c

Validated in BRCA2 mutation carriers. ORs and RAFs taken from Antoniou et al.136,137

d

Based on the nine validated SNP from Antoniou et al.136 and the six SNPs from Turnbull et al.131 that have not yet been validated in BRCA2 mutation carriers.

Source: reproduced with permission from Ingham SL, Warwick J, Byers H, Lalloo F, Newman WG, Evans DGR. Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK. Clinical Genetics 2013, 84:1, 37–42, © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.140

From: Chapter 3, Project 2: assessment of predictive value of new genetic variants

Cover of Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study
Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study.
Programme Grants for Applied Research, No. 4.11.
Evans DG, Astley S, Stavrinos P, et al.
Southampton (UK): NIHR Journals Library; 2016 Aug.
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