Germline Missense Variants in the BTNL2 Gene Are Associated with Prostate Cancer Susceptibility

DOI: 10.1158/1055-9965.EPI-13-0345 Published September 2013

Article Figures & Data

Download figure
Open in new tab
Download powerpoint
Figure 1.
HPC pedigrees of 2 families with segregating BTNL2 variants. Participants selected for WES in 19 HPC families are indicated by arrows. Affected men indicated by black shading. The remaining symbols are described in the key. Squares indicate males and circles indicate females. The age at diagnosis of men with prostate cancer is shown under the squares. A slash through the symbol indicates that the individual is deceased. The carrier status of the female in family 11 was confirmed by Sanger sequencing.

Table 1.

Characteristics of 19 HPC families with WES data

Family ID	No. of HPC cases	Mean age at HPC diagnosis	No. of WES cases with aggressive HPC^a	No. of WES cases with early-onset HPC^a	No. of WES cases per family	No. of WES unaffected men per family
1	9	64.4	2	3	4	1
2	7	62.2	2	3	4
3	7	69.9	2	2	5	1
4	9	67.3	4	2	5	1
5	8	68.0	3	1	4	1
6	6	60.6	1	5	5
7	11	64.6	2	2	3	1
8	5	54.0	2	3	3^b	1
9	7	57.2	3	2	3
10	6	66.0	3	2	4
11	7	59.0	5	3	5^b
12	9	68.4	2	1	4	1
13	9	60.0	1	5	5
14	10	65.1	2	6	6	1
15	7	61.9	3	3	4
16	8	63.4	0	4	4
17	9	66.2	1	2	2	1
18	10	65.6	2	3	5	1
19	7	67.8	3	3	5	1
Total	151	63.8	43	55	80	11

↵^aA total of 23 cases had both aggressive and early-onset prostate cancer.
↵^bWES failed or was of low quality for one of the affected men in these families.

Table 2.

Results for SNVs^a identified by WES and genotyped in 270 independent HPC families of European ancestry

						Discovery	Validation
Gene	Genomic position (hg19)	Variant and rs ID	Protein	MAF in ESP	MAF in ClinSeq	No. of WES families with carriers (Aff/Unaff)^b	No. (%) of 270 families with affected carriers	MAF in 819 genotyped affected men^c	MAF in 496 genotyped unaffected men^c	P^d
BTNL2	Chr6: 32,363,888	C > T rs41441651	Missense: p.Asp336Asn	0.009	0.005	2 (10/0)	9 (3.33)	0.0073	0	0.0032
BTNL2	Chr6: 32,362,521	C > A rs28362675	Missense: p.Gly454Cys	0.008	0.005	2 (10/0)	8 (2.96)	0.0061	0	0.0070

↵^aTop ranked (P < 0.05) SNVs identified by WES of 19 HPC families.
↵^bNumber of affected carriers/number of unaffected carriers.
↵^cThe number of affected carriers for rs41441651 and rs28362675 is 12 and 10, respectively, in the 270 independent HPC families.
↵^dMonte Carlo–based one-sided P value from the PedGenie χ² test for association based on the 270 independent HPC families.

Table 3.

OR and 95% CI for prostate cancer associated with SNVs in BTNL2 in European Americans

↵^aAdjusted for age.
↵^bOne case is homozygous variant for both SNVs; 22 cases and 9 controls are heterozygous for both SNVs.

Files in this Data Supplement:

Supplementary Figure Legend - PDF - 59K, Legend for Supplementary Figure 1.
Supplementary Figure 1 - PDF - 53K, Flow diagram of results from family- and bioinformatics-based filtering of whole-exome sequencing data and confirmation steps.
Supplementary Table 1 - PDF - 109K, Information on the 174 single nucleotide variants identified by whole-exome sequencing.
Supplementary Table 2 - PDF - 61K, Information on the 22 insertion/deletions identified by whole-exome sequencing.
Supplementary Table 3 - PDF - 51K, Summary of the whole-exome sequencing statistics for the 91 members of 19 hereditary prostate cancer families.