. 2016 Jan 7;2(1):77–89. doi: 10.3233/BLC-150027

Table 3.

Summary of significant associations (p < 0.05) between candidate SNPs and prognostic and predictive endpoints in the NBCS patient series

Endpoint	Gene	SNP	M/ I	Info	HWE p^a	A1^b	A2^b	Genotype counts		Model
				(NBCS1/ NBCS2)				(A1A1/A1A2/A2A2)^c			Unadjusted		Adjusted^d
								Event	No event		HR (95% CI)	p^e	HR (95% CI)	p^e
NMIBC –recurrence	RGS13	rs3795617	M	M	1	C	T	136/318/144	204/335/147	ADD	1.13 (1.01–1.27)	0.033	1.12 (0.99–1.26)	0.080
										DOM	1.26 (1.04–1.53)	0.016	1.20 (0.98–1.47)	0.085
										REC	1.10 (0.91–1.33)	0.308	1.12 (0.92–1.37)	0.268
BCG-treated	ERCC2	rs1799793^f	I	0.927 0.904	0.74	C	T	27/31/15	49/62/8	ADD	1.49 (1.03–2.15)	0.033	1.55 (1.05–2.31)	0.029
NMIBC –recurrence										DOM	1.21 (0.73–2.00)	0.462	1.16 (0.67–2.01)	0.594
										REC	2.76 (1.53–4.99)	7.88×10^–4	3.41 (1.79–6.47)	1.80×10^–4
BCG-treated	IL18	rs187238^f	I	0.999 0.998	0.54	C	G	35/28/10	65/48/6	ADD	1.38 (0.97–1.96)	0.073	1.74 (1.18–2.57)	5.49×10^–3
NMIBC –recurrence										DOM	1.25 (0.79–1.98)	0.340	1.59 (0.97–2.62)	0.066
										REC	2.35 (1.20–4.59)	0.013	3.57 (1.65–7.72)	1.20×10^–3
TUR-only-treated	SUFU	rs11594179	M	M	0.49	C	T	150/90/3	143/62/15	ADD	0.95 (0.76–1.18)	0.635	0.99 (0.79–1.24)	0.929
NMIBC –recurrence										DOM	1.09 (0.84–1.42)	0.497	1.17 (0.89–1.53)	0.255
										REC	0.23 (0.07–0.72)	0.012	0.24 (0.08–0.75)	0.014
NMIBC	RGS4	rs6678136^f	M	M	1	G	A	55/105/37	389/506/192	ADD	1.18 (0.97–1.43)	0.103	1.15 (0.93–1.44)	0.205
–progression										DOM	1.39 (1.02–1.90)	0.038	1.31 (0.92–1.85)	0.130
										REC	1.08 (0.75–1.54)	0.677	1.09 (0.74–1.63)	0.653
NMIBC	RGS5	rs11585883^f	I	0.984 0.986	0.06	T	C	166/29/2	936/150/1	ADD	1.20 (0.83–1.75)	0.339	1.21 (0.80–1.81)	0.367
–progression										DOM	1.13 (0.76–1.66)	0.548	1.13 (0.74–1.72)	0.585
										REC	10.0 (2.47–40.6)	1.27×10^–3	6.76 (1.57–29.2)	0.010
MIBC –overall	RGS5	rs12035879^f	I	0.619 0.607	4.7×10^–3	G	A	23/44/20	62/101/24	ADD	1.72 (1.13–2.61)	0.011	1.49 (0.97–2.29)	0.066
survival										DOM	1.76 (0.88–3.54)	0.110	1.63 (0.78–3.43)	0.195
										REC	2.79 (1.40–5.56)	3.47×10^–3	2.10 (1.01–4.37)	0.048
MIBC –overall	TERT	rs2075786^f	I	0.719 0.721	0.19	G	A	34/36/17	81/86/21	ADD	1.27 (0.90–1.80)	0.171	1.56 (1.09–2.24)	0.015
survival										DOM	1.18 (0.71–1.97)	0.527	1.47 (0.88–2.47)	0.142
										REC	1.93 (1.01–3.68)	0.045	2.97 (1.50–5.90)	1.81×10^–3

^aHWE p-value was calculated based on measured or best-guess genotypes in the total group of study subjects included for imputation (n = 1,601). ^bA1: major/reference allele; A2: minor/predictive allele (both according to plus (+) strand orientation). ^cExpected genotype counts for imputed SNPs were calculated using SNPTEST v2 based on the sum of probabilities across all individuals in the respective patient subgroup, and rounded to the nearest whole number. ^dIn NMIBC (subgroups): adjusted for gender (male/female), age (<60/60–70/>70 yrs), tumor stage (Ta/T1/CIS), tumor grade (low/ high grade), concomitant CIS (no/yes), tumor focality (solitary/multifocal), and in case of analysis of the total NMIBC group, treatment (TURT only±1 p.o. CT instillation/ adjuvant i.v. CT/ adjuvant i.v. IT/ both adjuvant i.v. CT and IT); In MIBC: adjusted for gender (male/female), age (continuous), and aggregate measure based on TNM classification (i.e. tumors of stage T2-T4a with N0/NX and M0/MX vs. tumor of stage T4(b) ór any T with N ≥1/N+ and/or M1). ^eValues in boldface type indicate significance at P < 0.05. ^fSNPs with directionally consistent association compared with original publication. Abbreviations: ADD: additive; BCG: bacillus Calmette-Guérin; CI: confidence interval; DOM: dominant; HR: hazard ratio; HWE: Hardy-Weinberg equilibrium; I: imputed; M: measured (genotyped); MIBC: muscle-invasive or metastatic bladder cancer; NMIBC: non-muscle-invasive bladder cancer; REC: recessive; SNP: single nucleotide polymorphism; TUR: transurethral resection.