Genetic Variation in the TGF-β Signaling Pathway and Colon and Rectal Cancer Risk

Martha L. Slattery; Jennifer S. Herrick; Abbie Lundgreen; Roger K. Wolff

doi:10.1158/1055-9965.EPI-10-0843

DOI: 10.1158/1055-9965.EPI-10-0843 Published January 2011

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Figure 1.
Associations between SNPs in the TGF-β signaling pathway and colon and rectal cancer.

Table 1.

Summary of SNPs

						Colon		Rectal
Gene	Alias	Location	SNP	Major/Minor allele	MAF^a	Heterozygote OR (95% CI)	Homozygote rare OR (95% CI)	Heterozygote OR (95% CI)	Homozygote rare OR (95% CI)
Smad2	MAD2	18q21.1	rs1787199	A/T	0.46	1.08 (0.92–1.26)	1.24 (1.03–1.51)	0.85 (0.69–1.05)^b
	MADH2		rs1792689	C/T	0.13	0.96 (0.82–1.12)	1.30 (0.79–2.13)	0.78 (0.62–0.98)^b
	JV18		rs4940086	T/C	0.33	1.08 (0.94–1.25)	1.33 (1.06–1.66)	1.00 (0.81–1.23)	1.05 (0.77–1.42)
Smad3	MAD3	15q22.33	rs750766	G/A	0.48	0.98 (0.84–1.15)	0.93 (0.77–1.13)	1.09 (0.89–1.34)^b
	MADH3		rs893473	C/T	0.17	0.97 (0.84–1.13)	0.99 (0.69–1.40)		1.09 (0.73–1.62)^c
	JV15-2		rs991157	G/A	0.3		0.93 (0.73–1.18)^c		1.11 (0.79–1.55)^c
			rs1498506	A/C	0.48	0.87 (0.75–1.02)	0.69 (0.57–0.84)	1.10 (0.88–1.38)	0.96 (0.72–1.26)
			rs1866317	C/G	0.11	0.98 (0.83–1.16)	0.92 (0.48–1.76)	1.12 (0.88–1.42)	1.65 (0.77–3.54)
			rs2118610	G/A	0.45	1.11 (0.95–1.29)	0.94 (0.78–1.14)	1.02 (0.82–1.27)	1.02 (0.77–1.36)
			rs2118611	A/G	0.2	1.03 (0.90–1.19)^b		0.89 (0.73–1.09)^b
			rs2414937	G/C	0.2		0.68 (0.47–0.97)^c	1.01 (0.82–1.24)	1.02 (0.63–1.67)
			rs3743343	T/C	0.24	1.10 (0.95–1.26)	1.15 (0.87–1.52)	0.97 (0.79–1.19)	1.10 (0.77–1.58)
			rs3825977	C/T	0.19	0.95 (0.82–1.11)	1.01 (0.72–1.42)	0.96 (0.78–1.18)	0.76 (0.47–1.24)
			rs4147358	C/A	0.22	1.08 (0.93–1.24)	0.99 (0.73–1.33)	1.03 (0.84–1.27)	0.89 (0.60–1.33)
			rs4776892	A/T	0.18	1.02 (0.89–1.18)^b		0.94 (0.76–1.16)	1.14 (0.69–1.88)
			rs7163381	G/A	0.26		0.76 (0.59–0.98)^c		1.11 (0.79–1.56)^c
			rs7176870	A/G	0.43	1.08 (0.93–1.24)^b		1.16 (0.94–1.42)^b
			rs11071933	C/G	0.33	1.04 (0.90–1.20)	0.94 (0.75–1.16)	0.84 (0.69–1.03)^b
			rs12901071	A/G	0.34		0.68 (0.55–0.85)^c		0.80 (0.57–1.10)^c
			rs17293443	T/C	0.22		0.84 (0.60–1.18)^c		1.81 (1.12–2.91)^c
Smad4	DPC4	18q21.1	rs10502913	G/A	0.24	1.03 (0.89–1.19)	0.81 (0.61–1.08)	1.02 (0.83–1.25)	1.09 (0.72–1.67)
	MADH4
TGFβ1	TGFB	19q13.1	rs1800469	G/A	0.31	0.89 (0.78–1.03)	0.65 (0.51–0.84)	1.02 (0.84–1.23)^b
			rs4803455	C/A	0.48	1.25 (1.06–1.47)	1.43 (1.18–1.73)	1.06 (0.84–1.32)	1.04 (0.79–1.35)
TGFβR1	ALK-5	9q22	rs1571590	A/G	0.2	0.95 (0.82–1.10)	1.39 (0.98–1.96)	0.91 (0.74–1.12)	1.42 (0.85–2.39)
	SKR4		rs6478974	T/A	0.49	0.85 (0.74–0.99)^b		0.85 (0.69–1.05)^b
	LDS1A		rs10733710	G/A	0.2	1.07 (0.93–1.23)^b		1.17 (0.96–1.43)^b
	AAT5

↵^aMAF based on White control population.
↵^bDominant model.
↵^cRecessive model.

Table 2.

Interaction between variants in the TGF-β signaling pathway and NFκB1 and IKBκB and risk of colon cancer^a

	Controls, n	Cases, n	OR	95% CI	Controls, n	Cases, n	OR	95% CI	Controls, n	Cases, n	OR	95% CI
	TGFβ1 rs1800469
	GG				GA				AA
Smad3 rs3825977
CC	610	521	1.00		542	419	0.92	0.77 1.09	116	80	0.80	0.58 1.08
CT	277	230	0.99	0.80 1.23	259	201	0.90	0.72 1.12	68	35	0.57	0.37 0.88
TT	30	43	1.67	1.03 2.70	35	19	0.64	0.36 1.14	13	2	0.17	0.04 0.75
P_interaction			<0.01
	TGFβ1 rs4803455
	CC				CA				AA
Smad2 rs4940086
TT	232	152	1.00		465	360	1.21	0.94–1.55	207	170	1.27	0.95–1.70
TC	228	162	1.10	0.83–1.47	425	335	1.24	0.96–1.59	196	180	1.46	1.09–1.95
CC	58	26	0.71	0.43–1.18	105	113	1.71	1.22–2.39	29	50	2.72	1.64–4.49
P_interaction			0.02
Smad3 rs17293443
TT/TC	485	330	1.00		947	779	1.23	1.04–1.45	420	380	1.35	1.11–1.64
CC	33	10	0.46	0.22–0.94	48	29	0.93	0.57–1.51	11	20	2.92	1.38–6.19
P_interaction			<0.01
Smad7 rs4939827
TT	115	106	1.00		255	225	0.99	0.72–1.37	123	110	0.99	0.69–1.44
TC/CC	403	233	0.63	0.46–0.86	738	582	0.87	0.65–1.16	309	290	1.04	0.76–1.42
P_interaction			0.02
	TGFβR1 rs6478974
	CC				CA				AA
IKBκB rs3747811
TT	148	155	1.00		255	208	0.78	0.58–1.05	124	84	0.66	0.46–0.95
TA	270	219	0.78	0.58–1.04	472	352	0.72	0.55–0.95	250	171	0.67	0.49–0.90
AA	115	104	0.87	0.61–1.24	239	171	0.69	0.51–0.94	83	90	1.04	0.71–1.52
P_interaction			0.04
NFκB1 rs4648110
TT	346	289	1.00		615	474	0.93	0.76–1.14	282	233	1.01	0.80–1.28
TA	163	175	1.29	0.99–1.68	311	234	0.91	0.72–1.15	156	105	0.82	0.61–1.10
AA	24	14	0.71	0.36–1.40	40	23	0.69	0.40–1.18	19	7	0.47	0.20–1.15
P_interaction			0.04
	TGFβR1 rs1571590
	AA				AG				GG
IKBκB rs3747811^b
TT	347	268	1.00		166	156	1.24	0.94–1.62	14	23	2.24	1.13–4.44
TA	640	500	1.03	0.85–1.26	317	209	0.86	0.68–1.09	35	33	1.25	0.75–2.06
AA	273	239	1.14	0.90–1.44	147	111	1.01	0.75–1.36	17	16	1.24	0.61–2.51
P_interaction			0.04

↵^aAssociations adjusted for age, sex, center and race.
↵^bSimilar associations were observed for NFκB1 rs13117745 (C > T), P_interaction = 0.02.

Table 3.

Associations between variants in the TGF-β signaling pathway and NFκB1 and Smad2 and Smad3 and rectal cancer risk^a

	Controls, n	Cases, n	OR	95% CI	Controls, n	Cases, n	OR	95% CI	Controls, n	Cases, n	OR	95% CI
	TGFβ1 rs1800469
	GG				GA				AA
Smad3 rs2118610^b
GG	158	119	1.00		140	104	0.99	0.70–1.40	23	35	1.95	1.09–3.48
GA	224	166	1.03	0.75–1.40	178	156	1.18	0.86–1.63	52	35	0.91	0.56–1.49
AA	83	72	1.22	0.82–1.81	76	61	1.11	0.73–1.68	19	4	0.29	0.10–0.88
P_interaction			0.01
Smad3 rs4147358^c
CC	254	204	1.00		220	181	1	0.76–1.31	63	31	0.58	0.36–0.93
CA	184	137	0.89	0.89–1.19	138	115	0.99	0.72–1.35	26	34	1.59	0.92–2.74
AA	27	16	0.67	0.35–1.28	36	25	0.83	0.48–1.43	5	9	1.96	0.64–6.03
P_interaction			<0.01
	TGFβ1 rs4803455
	CC				CA				AA
NFκB1 rs13117745^d
CC	201	130	1.00		339	274	1.25	0.95–1.65	155	132	1.35	0.98–1.86
CT/TT	52	66	2.00	1.30–3.06	142	105	1.18	0.84–1.65	69	44	1.00	0.64–1.55
P_interaction			<0.01
	TGFβR1 rs10733710
	GG				GA/AA
NFκB1 rs4648110^e
TT	405	270	1.00		207	201	1.45	1.13–1.86
TA/AA	210	184	1.33	1.04–1.72	136	98	1.08	0.80–1.47
P_interaction			<0.01
	TGFβR1 rs1571590
	AA				AG				GG
Smad2 rs1792689
CC	455	379	1.00		241	183	0.91	0.72–1.16	15	28	2.42	1.27–4.61
CT/TT	156	112	0.84	0.63–1.11	78	48	0.75	0.51–1.11	14	4	0.32	0.10–0.99
P_interaction			0.003

↵^aAssociation adjusted for age, sex, race and center.
↵^bSimilar associations were observed for SMAD3 rs991157 (G > A), P_interaction < 0.01.
↵^cSimilar associations were observed for SMAD3 rs745103 (T > A), P_interaction < 0.01.
↵^dSimilar associations were observed for NFκB1 rs4648110 (T > A), P_interaction = 0.02.
↵^dSimilar associations were observed for NFκB1 rs13117745 (C > T), P_interaction = 0.01.

Table 4.

Interaction between genetic variants in the TGF-β signaling pathway and lifestyle factors and risk of colon and rectal cancer

	Controls, n	Cases, n	OR^a	95% CI	Controls, n	Cases, n	OR^a	95% CI
Colon cancer	Never smoker/Former smoker				Recent smoker
TGFβ1 rs4803455
CC	422	274	1.00		96	66	1.04	0.74–1.48
CA	815	650	1.25	1.04–1.50	180	155	1.31	1.01–1.71
AA	363	306	1.33	1.07–1.65	68	94	2.09	1.47–2.96
P_interaction			0.05
TGFβR1 rs10733710
GG	1,004	775	1.00		223	178	0.99	0.79–1.24
GA/AA	586	452	0.99	0.85–1.16	120	138	1.46	1.12–1.90
P_interaction			0.03
TGFβR1 rs1571590
AA	1,053	797	1.00		206	207	1.29	1.04–1.60
AG	505	376	0.99	0.84–1.17	125	101	1.04	(0.78–1.37)
GG	51	62	1.63	1.10–2.37	15	10	0.88	0.39–1.98
P_interaction			0.05
Rectal cancer
TGFβ1 rs1800469
GG	385	295	1.00		80	61	0.97	0.67–1.40
GA/AA	419	305	0.93	0.75–1.15	69	87	1.58	1.11–2.24
P_interaction			0.03
Colon cancer	No recent aspirin/NSAID use				Recent aspirin NSAID use
TGFβR1 rs6478974
TT	329	313	1.00		202	160	0.83	0.64–1.07
TA	554	502	0.95	0.78–1.16	401	223	0.59	0.47–0.74
AA	253	238	1.01	0.79–1.28	201	101	0.54	0.40–0.71
P_interaction			0.03
Smad3 rs3743343
TT	663	567	1.00		462	291	0.73	0.61–0.88
TC	402	401	1.15	0.96–1.38	295	177	0.70	0.56–0.87
CC	70	85	1.43	1.02–2.00	47	18	0.45	0.26–0.78
P_interaction			0.02
Smad3 rs7173811
CC	323	263	1.00		228	147	0.79	0.61–1.03
CT	549	520	1.15	0.94–1.41	378	235	0.77	0.61–0.96
TT	264	270	1.24	0.98–1.57	198	104	0.63	0.47–0.85
P_interaction			0.03
Rectal cancer
Smad3 rs3743343
TT	272	268	1.00		245	137	0.57	0.44–0.75
TC	205	173	0.84	0.65–1.10	156	105	0.69	(0.51–0.93)
CC	44	36	0.81	0.50–1.30	27	29	1.03	0.59–1.80
P_interaction			0.01
Smad3 rs7163381^c
GG	268	229	1.00		206	151	0.87	0.66–1.14
GA	219	198	1.04	0.80–1.35	176	96	0.63	0.46–0.86
AA	34	50	1.65	1.02–2.67	46	24	0.58	0.34–0.99
P_interaction			0.01
Colon cancer	No recent estrogen exposure				Recent estrogen exposure
TGFβ1 rs1800469
GG	253	209	1.00		653	579	0.78	0.59–1.03
GA	213	200	1.16	0.89–1.51	612	433	0.62	0.47–0.82
AA	53	39	0.85	0.54–1.34	141	77	0.47	0.32–0.68
P_interaction			0.03
Rectal cancer
TGFβ1 rs4803455
CC	40	40	1.00		213	155	0.53	0.32–0.90
CA	84	76	0.89	0.52–1.53	397	303	0.57	0.34–0.94
AA	45	25	0.54	0.28–1.05	179	151	0.64	0.38–1.08
P_interaction			0.04
Smad4 rs10502913^c	Men				Women
GG	318	245	1.00		248	197	1.04	0.81–1.33
GA	196	174	1.17	0.90–1.53	144	94	0.86	0.63–1.17
AA	26	32	1.57	0.91–2.72	25	12	0.64	0.31–1.30
P_interaction			0.02

↵^aAdjusted for age, center, race, and sex.
^bSimilar association observed for Smad3 rs11071933; P_interaction = 0.03.
↵^cSimilar associations observed for Smad4 rs8096092; P_interaction = 0.02.

Table 5.

Associations between tumor molecular phenotype and TGFβ and Smad genes

		Controls, n	Cases, n	OR^a	95% CI
Colon tumors		CIMP+
Smad2 rs1787199	AA	601	64	1.00
Note: Similar results for rs4940086	AT/TT	1,355	208	1.46	1.09–1.97
Smad3 rs2118611^b	AA	1,226	152	1.00
	AG/GG	729	120	1.87	1.26–2.79
Smad3 rs4776892	AA	1,288	175	1.00
	AT/TT	667	97	0.63	0.42–0.95
		KRAS2 mutation
TGFβ1 rs4803455	CC	526	74	1.00
	CA/AA	1,457	280	1.40	1.06–1.85
TGFβ1 rs1800469	GG	932	187	1.00
	GA/AA	1,046	166	0.78	0.62–0.98
		TP53 mutation
Smad2 rs4940086	TT/TC	1,762	449	1.00
	CC	194	67	1.38	1.02–1.86
Smad3 rs7176870	AA	644	146	1.00
	AG/GG	1,311	371	1.28	1.03–1.59
TGFβ1 rs4803455	CC	526	111	1.00
	CA	1,014	267	1.27	0.99–1.63
	AA	443	144	1.56	1.18–2.07
TGFβ1 rs1800469	GG	932	275	1.00
	GA/AA	1,046	243	0.78	0.64–0.95
		MSI unstable
Smad2 rs1792689	CC	1,477	132	1.00
Note: Similar results for rs1787199	CT	448	45	1.12	0.79–1.60
	TT	31	8	2.85	1.28–6.36
Smad3 rs12901071^b	AA/AG	1,716	174	1.00
Note: Similar results for rs731874	GG	240	11	0.43	0.23–0.83
TGFβ1 rs1800469	GG	932	110	1.00
	GA/AA	1,046	80	0.64	0.47–0.86
Rectal tumors		CIMP+
Smad3 rs893473	CC/CT	899	49	1.00
	TT	60	10	3.60	1.62–7.98
TGFβR1 rs10733710	GG	615	27	1.00
	GA/AA	343	32	2.10	1.24–3.57
		KRAS2 mutation
Smad3 (rs991157)	GG/GA	876	150	1.00
	AA	83	23	1.69	1.03–2.79
		TP53 mutation
Smad3 rs11071933^b	CC	385	127	1.00
	CG/GG	572	150	0.72	0.54–0.95
Smad3 rs750766	GG	304	70	1.00
Note: Similar results for rs12102171 and rs7176870	GA/AA	653	207	1.49	1.09–2.04
TGFβR1 rs10733710	GG	615	155	1.00
	GA/AA	343	105	1.40	1.06–1.84

↵^aAdjusted for age, center, sex, and race.
↵^btagSNPs presented for this gene are adjusted for one another.

Summary of All Genes and SNPs Assessed

Gene	Chromosome location	SNP	Region	MAF	Major/Minor allele	FDR HWE probability	Colon homozygote are OR	Rectal homozygote rare OR
Smad1	4q31	rs714195	Intronic	0.42	G/A	0.73	0.99 (0.80–1.21)	1.02 (0.74–1.39)
		rs6537355	5 upstream	0.12	A/G	0.88	1.35 (0.72–2.54)	0.93 (0.37–2.32)
		rs2118438	Intronic	0.19	G/A	0.61	1.11 (0.75–1.65)	1.29 (0.72–2.34)
		rs1016792	Intronic	0.19	T/C	1.00	1.00 (0.69–1.46)	0.90 (0.51–1.58)
		rs12505085	3 downstream	0.23	A/G	0.89	0.88 (0.65–1.20)	0.91 (0.57–1.47)
Smad2	18q21.1	rs1787199	Intronic	0.46	A/T	1.00	1.24 (1.03–1.51)	0.83 (0.63–1.08)
		rs1792658	Intronic	0.21	A/C	0.96	1.18 (0.88–1.58)	1.12 (0.72–1.74)
		rs1792689	Intronic	0.13	C/T	0.95	1.30 (0.79–2.13)	0.95 (0.41–2.22)
		rs4940086	Intronic	0.33	T/C	1.00	1.33 (1.06–1.66)	1.05 (0.77–1.42)
Smad3	15q22.33	rs731874	Intronic	0.28	G/A	1.00	1.06 (0.82–1.37)	0.94 (0.65–1.37)
		rs745103	Intronic	0.45	T/C	0.86	0.96 (0.79–1.16)	0.98 (0.75–1.29)
		rs750766	Unknown	0.48	G/A	1.00	0.93 (0.77–1.13)	1.06 (0.81–1.39)
		rs893473	Intronic	0.17	C/T	1.00	0.99 (0.69–1.40)	1.06 (0.71–1.59)
		rs991157	Intronic	0.30	G/A	1.00	0.96 (0.75–1.23)	1.07 (0.75–1.51)
		rs1470003	Intronic	0.48	G/C	0.96	0.95 (0.79–1.15)	1.19 (0.90–1.57)
		rs1498506	Intronic	0.48	A/C	1.00	0.69 (0.57–0.84)	0.96 (0.72–1.26)
		rs1866317	Unknown	0.11	C/G	1.00	0.92 (0.48–1.76)	1.65 (0.77–3.54)
		rs1992215	Unknown	0.33	T/C	1.00	1.00 (0.80–1.25)	0.86 (0.62–1.21)
		rs2118610	Intronic	0.45	G/A	0.61	0.94 (0.78–1.14)	1.02 (0.77–1.36)
		rs2118611	Intronic	0.20	A/G	0.99	0.94 (0.66–1.34)	0.93 (0.62–1.42)
		rs2414937	Intronic	0.20	G/C	1.00	0.67 (0.47–0.97)	1.02 (0.63–1.67)
		rs3743343	3 UTR	0.24	T/C	1.00	1.15 (0.87–1.52)	1.10 (0.77–1.58)
		rs3784681	Intronic	0.29	G/C	0.96	0.91 (0.71–1.17)	0.79 (0.56–1.11)
		rs3825977	Intronic	0.19	C/T	1.00	1.01 (0.72–1.42)	0.76 (0.47–1.24)
		rs4147358	Intronic	0.22	C/A	0.96	0.99 (0.73–1.33)	0.89 (0.60–1.33)
		rs4601989	Intronic	0.24	C/T	0.68	0.81 (0.60–1.08)	0.66 (0.44–1.00)
		rs4776881	Intronic	0.44	T/C	1.00	1.07 (0.89–1.30)	1.21 (0.92–1.60)
		rs4776890	Intronic	0.40	T/G	0.96	0.97 (0.80–1.19)	0.96 (0.72–1.28)
		rs4776892	Intronic	0.18	A/T	0.45	1.00 (0.67–1.48)	1.14 (0.69–1.88)
		rs7163381	Intronic	0.26	G/A	1.00	0.79 (0.61–1.03)	1.06 (0.74–1.51)
		rs7173811	Intronic	0.47	C/T	0.96	1.06 (0.88–1.28)	0.96 (0.73–1.26)
		rs7176870	Intronic	0.43	A/G	1.00	1.06 (0.88–1.29)	1.19 (0.90–1.58)
		rs7181556	Intronic	0.24	C/T	0.99	0.91 (0.69–1.22)	0.75 (0.50–1.12)
		rs7183244	Intronic	0.39	C/T	0.84	1.00 (0.81–1.23)	1.04 (0.77–1.41)
		rs9972423	Intronic	0.37	T/A	1.00	0.97 (0.79–1.20)	1.27 (0.94–1.73)
		rs11071933	Intronic	0.33	C/G	1.00	0.94 (0.75–1.16)	0.92 (0.68–1.25)
		rs11637581	Intronic	0.28	C/T	0.95	0.98 (0.76–1.28)	1.11 (0.77–1.59)
		rs11639295	Intronic	0.31	C/T	1.00	0.88 (0.70–1.12)	0.83 (0.59–1.16)
		rs12102171	Intronic	0.17	C/T	0.86	0.90 (0.62–1.30)	0.84 (0.49–1.43)
		rs12708492	Intronic	0.48	C/T	1.00	1.02 (0.85–1.24)	1.10 (0.84–1.44)
		rs12901071	Intronic	0.34	A/G	0.68	0.67 (0.53–0.84)	0.85 (0.60–1.20)
		rs12904944	Intronic	0.34	G/A	1.00	0.81 (0.64–1.01)	1.07 (0.79–1.47)
		rs12907997	Intronic	0.50	C/T	1.00	0.95 (0.78–1.14)	0.91 (0.70–1.20)
		rs12915039	Intronic	0.24	A/C	1.00	1.01 (0.76–1.35)	1.08 (0.72–1.61)
		rs16950687	Intronic	0.28	A/G	1.00	0.93 (0.72–1.21)	1.22 (0.85–1.76)
		rs17293443	Intronic	0.22	T/C	0.92	0.85 (0.61–1.19)	1.74 (1.08–2.82)
Smad4	18q21.1	rs8096092	Intronic	0.38	C/A	0.68	1.00 (0.81–1.23)	1.17 (0.87–1.59)
		rs10502913	Intronic	0.24	G/A	0.74	0.81 (0.61–1.08)	1.09 (0.72–1.67)
Smad7	18q21.1	rs1316447	Intronic	0.19	C/T	1.00	0.86 (0.60–1.23)	0.88 (0.53–1.45)
		rs2337106	Intronic	0.47	C/G	1.00	0.88 (0.72–1.06)	1.11 (0.85–1.45)
		rs2337107	Intronic	0.41	G/A	0.99	1.12 (0.92–1.36)	0.97 (0.74–1.28)
		rs3736242	Intronic	0.22	G/A	1.00	0.94 (0.69–1.28)	1.33 (0.84–2.09)
		rs3764482	Intronic	0.19	C/T	1.00	1.25 (0.86–1.81)	0.60 (0.34–1.07)
		rs4464148	Intronic	0.31	T/C	1.00	1.06 (0.83–1.35)	0.76 (0.54–1.09)
		rs4939827	Intronic	0.49	T/C	1.00	0.79 (0.66–0.95)	0.95 (0.73–1.23)
		rs4939832	Intronic	0.24	A/G	1.00	1.00 (0.76–1.32)	1.29 (0.87–1.92)
		rs7238442	Intronic	0.46	T/C	0.82	1.12 (0.93–1.35)	0.92 (0.71–1.20)
		rs12456328	Intronic	0.13	C/T	1.00	0.81 (0.49–1.33)	1.16 (0.51–2.66)
		rs12953717	Intronic	0.42	C/T	1.00	1.36 (1.12–1.65)	0.90 (0.68–1.19)
TGFβ1	19q13.1	rs1800469	5 upstream	0.31	G/A	1.00	0.65 (0.51–0.84)	0.98 (0.71–1.38)
		rs4803455	Intronic	0.48	C/A	0.92	1.43 (1.18–1.73)	1.04 (0.79–1.35)
TGFβR1	9q22	rs1571590	Intronic	0.20	A/G	0.67	1.39 (0.98–1.96)	1.42 (0.85–2.39)
		rs6478974	Intronic	0.49	T/A	1.00	0.86 (0.71–1.04)	0.84 (0.63–1.10)
		rs10733710	Intronic	0.20	G/A	0.96	1.06 (0.77–1.46)	1.22 (0.78–1.91)