Toll-like Receptor Signaling Pathway Variants and Prostate Cancer Mortality

Jennifer R. Stark; Fredrik Wiklund; Henrik Grönberg; Fredrick Schumacher; Jennifer A. Sinnott; Meir J. Stampfer; Lorelei A. Mucci; Peter Kraft

doi:10.1158/1055-9965.EPI-08-0981

DOI: 10.1158/1055-9965.EPI-08-0981 Published June 2009

Article Figures & Data

Tables

Additional Files

Table 1.

Demographic and tumor characteristics of the 1,252 CaPS cases (2001-2002)

Characteristic
Age at diagnosis, median (range), y	65.9 (47.3-80.4)
Years of follow-up, median (range)	5.1 (0.4-6.5)
Family history, n (%)
None	1088 (86.9)
1 blood relative	118 (9.4)
≥2 blood relatives	46 (3.7)
T stage, n (%)
T₁	428 (34.2)
T₂	377 (30.1)
T₃	239 (19.1)
T₄/N₁/M₁	176 (14.0)
Missing	32 (2.6)
Gleason, n (%)
2-5	182 (14.5)
6	405 (32.4)
7	338 (27.0)
8-10	192 (15.3)
Missing	135 (10.8)
Curative treatment,* n (%)	602 (48.1)
Hormonal therapy,^† n (%)	577 (46.1)

↵* Curative treatment includes radical prostatectomy or radiation.
↵† Includes medical and surgical hormone therapy.

Table 2.

Distribution of SNPs and likelihood ratio test P values from Cox proportional hazards models of prostate cancer mortality among 1,252 cases

Gene	rs number	Location	Variation	Minor allele frequency	LRT P value*
Gene	rs number	Location	Variation	Minor allele frequency			Multivariate model 1^†	Multivariate model 2^‡
COX-2	rs2745557	202	C>T	0.17	0.93	0.89
	rs5275	6,365	T>C	0.35	0.24	0.48
	rs4648276	3,935	T>C	0.11	0.91	0.97
	rs689470	8,365	C>T	0.03	0.79	0.97
	rs20432	3,100	T>G	0.14	0.76	0.94
IL-1RN	rs878972	2,118	A>C	0.26	0.48	0.78
	rs315934	8,111	T>C	0.19	0.98	0.99
	rs3087263	10,173	G>A	0.09	0.96	0.70
	rs315951	14,992	C>G	0.33	0.09	0.09
IL-6	rs1474348	1,027	G>C	0.49	0.70	0.78
	rs2069845	3,268	G>A	0.48	0.15	0.29
	rs1800795	−237	G>C	0.49	0.44	0.79
	rs1800796	−636	G>C	0.04	0.80	0.64
	rs1800797	−661	G>A	0.49	0.62	0.89
IL-10	rs1800871	−853	C>T	0.26	0.66	0.46
	rs1800872	−627	C>A	0.27	0.66	0.46
	rs3024509	2,483	T>C	0.07	0.89	0.94
	rs3024505	5,876	C>T	0.12	0.66	0.29
	rs1800896	−1,117	A>G	0.46	0.80	0.83
	rs1554286	1,547	C>T	0.22	0.78	0.55
IRAK1	rs1059702	1,071 (F196S)	C>T	0.12	0.86	0.79
	rs7061789	4,788	T>C	0.18	0.98	0.99
	rs1059703	6,434 (S532L)	T>C	0.13	0.80	0.87
	rs3027878	9,373	T>G	0.18	0.99	0.99
IRAK4	rs1057190	−13,656	T>C	0.11	0.36	0.40
	rs4251431	−7,225	G>T	0.09	0.70	0.92
	rs4251571	−2,001	A>G	0.02	0.43	0.15
	rs4251459	652	T>C	0.11	0.36	0.44
	rs4251487	7,987	G>C	0.02	0.58	0.44
	rs4251545	18,380 (A428G)	G>A	0.10	0.71	0.87
	rs4251559	20,791	A>G	0.44	0.66	0.58
MIC-1	rs1058587	Exon2 +2,423	C>G	0.28	0.95	0.99
	rs1059519	Exon1 +25	C>G	0.29	0.14	0.53
	rs1059369	Exon1 +142	A>T	0.27	0.30	0.41
	rs1227732	IVS1 +1,809	G>T	0.16	0.002^§	0.009
MyD88	rs4988453	−938	C>A	0.06	0.39	0.19
TIRAP	rs646005	9,537	T>C	0.37	0.71	0.79
	rs8177376	14,115	T>G	0.24	0.96	0.80
	rs12290468	17,678	G>A	0.05	0.71	0.99
TLR1	rs5743551	−7,202	A>G	0.23	0.02	0.03
	rs5743556	−6,399	T>C	0.15	0.21	0.35
	N/A	−2,299	T>C	0.18	0.82	0.98
	rs5743604	−833	T>C	0.30	0.04	0.06
	rs5743611	238	G>C	0.11	0.98	0.89
	rs4624663	2,576	A>G	0.04	0.96	0.99
TLR2	rs3804099	596	T>C	0.43	0.58	0.61
	rs3804100	1,349	T>C	0.06	0.26	0.38
TLR3	rs3775296	−7	C>A	0.18	0.78	0.94
	rs5743313	2,593	C>T	0.18	0.82	0.92
	rs3775291	6,301	C>T	0.30	0.92	0.44
	rs5743303	−8,921	A>T	0.17	0.75	0.94
	rs5743305	8,441	T>A	0.33	0.80	0.80
TLR4	rs11536889	−11,380	G>C	0.12	0.84	0.74
	rs10759932	−1,607	T>C	0.15	0.99	0.86
	rs2149356	IVS3−468	G>T	0.30	0.64	0.56
	rs4986790	8,551	A>G	0.05	0.87	0.99
	rs1927914	−2,026	A>G	0.33	0.72	0.88
	rs10759933	3,622	A>C	0.05	0.99	0.96
	rs5030721	9,615	G>A	0.01	0.94	0.86
	rs11536871	3,748	A>C	0.02	0.92	0.97
	rs7873784	12,185	G>C	0.14	0.96	0.97
	rs11536891	17,050	T>C	0.14	0.86	0.99
TLR5	n/a	−27,694	C>T	0.48	0.39	0.17
	rs2241096	−23,799	C>T	0.12	0.98	0.92
	rs2072493	1,774	A>G	0.15	0.99	0.94
	rs5744174	1,845	T>C	0.48	0.73	0.56
	rs1053954	2,533	A>G	0.08	0.75	0.71
TLR6	rs5743788	−2,113	C>G	0.50	0.09	0.16
	rs5743795	−1,401	G>A	0.18	0.16	0.31
	rs5743806	−673	G>C	0.32	0.09	0.11
	rs5743810	744	C>T	0.40	0.17	0.30
	rs5743815	1,279	T>C	0.02	0.71	0.93
TLR7	rs2302267	−120	T>G	0.06	0.78	0.87
	rs179019	4,271	C>A	0.23	0.99	0.95
	rs179016	8,744	G>C	0.41	0.32	0.58
	rs1620233	12,381	C>T	0.10	0.10	0.20
	rs179008	17,961	A>T	0.25	0.95	0.84
TLR8	rs1548731	−558	C>T	0.26	0.62	0.99
	rs4830806	3,467	C>T	0.39	0.84	0.55
	rs5744068	6,553	C>T	0.16	0.83	0.97
	rs5744080	9,299	C>T	0.36	0.99	0.99
	rs5744088	12,059	G>C	0.16	0.83	0.98
TLR9	rs187084	−1,486	T>C	0.44	0.009^∥	0.05
TLR10	rs11466617	−3,260	T>C	0.16	0.12	0.12
	rs11466640	−1,692	C>T	0.17	0.27	0.41
	rs4274855	−260	G>A	0.17	0.32	0.52
	rs11096957	720 (N241H)	A>C	0.37	0.04	0.06
	rs11096955	1,104 (1369L)	A>C	0.36	0.09	0.18
	rs11466657	1,417 (1473T)	T>C	0.02	0.36	0.22
	rs4129009	2,332 (1775V)	A>G	0.17	0.25	0.34
TNF-α	rs1799724	G1−857	C>T	0.07	0.99	0.99
	rs1800750	G1−376	G>A	0.01	0.72	0.81
	rs3093662	G1-IVS1 −122	A>G	0.04	0.96	0.87
	rs361525	G2−238	G>A	0.03	0.99	0.99
	rs3093664	G2-IVS3 +51	A>G	0.07	0.56	0.79
	rs3093665	G3-EX4 +499	A>C	0.01	0.44	0.29
	rs1800629	TNFa −308	G>A	0.18	0.11	0.12
	rs769178	G4-3′ +1402	G>T	0.07	0.99	0.99
	rs1800630	G5−863	C>A	0.17	0.94	0.76

NOTE: HRs (99% CIs) are shown in Supplementary Table 1.
Abbreviations: LRT, likelihood ratio test.
↵* From a Cox proportional hazards model of the codominant genotype when the frequency of rare heterozygotes >0.05 and from a dominant genotype otherwise.
↵† Controlling for age and geographic location.
↵‡ Controlling for age, geographic location, and indicator variables for curative and hormonal treatment.
↵§ HR (99% CI) for GT/TT versus GG: 0.54 (0.34, 0.87).
↵∥ HR (99% CI) for TC versus TT: 1.57 (1.02, 2.41); CC versus TT: 1.02 (0.57, 1.84).