Rare key functional domain missense substitutions in MRE11A, RAD50, and NBNcontribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study

Table 5 Analyses of potentially pathogenic groups of rare variants

Class	Cases, n	Controls, n	Crude OR^†(95% CI)	Adjusted OR^†(95% CI)
Noncarriers	1,283	1,114
T + SJV^¥
MRE11A	1	0
RAD50^$	4	3
NBN	4	0
Total	9	3	2.60 (0.70-9.65)	2.61 (0.67-10.1)
Any key functional domain rMS or in-frame indel^*
MRE11A^¢	10	1
RAD50	10	2
NBN	4	2
Total	24	5	4.18 (1.59-11.0)	3.17 (1.17-8.59)
Key functional domain rMS (severity > C0) or in-frame indel^*
MRE11A^¢	7	1
RAD50	10	2
NBN	3	1
Total	20	4	4.34 (1.48-12.7)	3.07 (1.01-9.31)
T + SJV^¥ plus key functional domain rMS (severity > C0) or in-frame indel^*
MRE11A^¢	8	1
RAD50^$	14	5
NBN	7	1
Total	29	7	3.60 (1.57-8.24)	2.88 (1.22-6.78)

Boldface within the table indicates P <0.05. ^†In these binary logistic regressions, the regression coefficient = ln(OR). ^¥Truncating and splice junction variants; excludes final exon nonsense and frameshift variants. ^$One subject (a case) carried both the RAD50 splice acceptor variant RAD50_c.552-1G > A and the RAD50 silent substitution RAD50 c.3153G > A (p.L1051L). ^*The key functional domains are defined in Figure 1. The set of variants includes rare missense substitutions with A-GVGD scores > C0, and final exon nonsense and frameshift variants if they also fall in a key functional domain. ^¢One subject (a case) carried both the MRE11A key domain rare missense substitution MRE11A p.D235G and the NBN non key domain rare missense substitution NBN p.V210F. OR, odds ratio; CI, confidence interval.

ISSN: 1465-542X