Association of β-Catenin, APC, SMAD3/4, Tp53, and Cyclin D1 Genes in Colorectal Cancer: A Systematic Review and Meta-Analysis

Table 2

Hazard ratios of studies included in meta-analysis.

No.	Author	Year	Gene	Outcome	HR	95% CI
						Lower	Upper
1	Wang et al. (COH/UCD) [75]	2020	APC	OS	0.62	0.44	0.86
	Wang et al. (MSKCC) [75]		APC	OS	0.63	0.49	0.81
	Wang et al. (COH/UCD) [75]		CTNNB1	OS	0.95	0.35	2.55
	Wang et al. (MSKCC) [75]		CTNNB1	OS	1.67	0.86	3.26
	Wang et al. (COH/UCD) [75]		TP53	OS	1.33	0.93	1.88
	Wang et al. (MSKCC) [75]		TP53	OS	1.00	0.77	1.30
2	Mondaca et al. [76]	2020	APC	Progression-free survival	0.68	0.54	0.86
				OS	0.56	0.42	0.75
			CTNNB1	Progression-free survival	1.63	0.97	2.74
				OS	1.18	0.64	2.19
3	Gerami et al. [78]	2020	APC	OS	3.24	1.21	8.68
4	Jorissen et al. (MSI) [81]	2015	APC	OS	0.90	0.27	2.96
				RFS	1.26	0.25	6.50
	Jorissen et al. (MSS) [81]	2015	APC	OS	2.01	1.17	3.43
				RFS	2.71	1.39	5.28
	Jorissen et al. (Validation cohort, MSS) [81]	2015	APC	OS	3.02	1.67	5.47
				RFS	2.14	1.10	4.18
5	Voorneveld et al. [82]	2012	SMAD-4	OS	2.47	1.02	4.15
6	Li et al. [83]	2011	SMAD-4	OS	7.04	3.88	12.82
7	Yoo et al. [84]	2019	SMAD-4	Progression-free survival	1.27	1.01	1.60
				Cancer-free survival	1.45	1.06	1.99
8	Su et al. [85]	2016	SMAD-4	DFS	0.92	0.69	1.222
				OS	0.87	0.64	1.187
9	Roth et al. [88]	2012	SMAD-4	OS	1.58	1.23	2.01
				RFS	1.47	1.19	1.81
10	Isaksson et al. [90]	2011	SMAD-4	OS	1.81	1.09	3.00
11	Chun et al. [95]	2014	SMAD-4 (nuclear)	OS	1.71	0.83	3.511
			SMAD-4 (cytoplasmic)	OS	1.15	0.57	2.30
12	Meskar et al. [97]	2009	SMAD4	OS	7.98	4.12	15.44
				DFS	6.57	3.43	12.56
13	Salim et al. [53]	2013	β catenin (membrane β-catenin absent + nuclear GSK3 β)	OS	1.98	1.01	3.89
14	Kamposioras et al. [54]	2013	β-Catenin (membrane)	DFS	0.33	0.14	0.77
15	Gao et al. [55]	2014	β-Catenin (membrane)	OS	1.13	0.62	2.05
			β-Catenin (nucleus)	OS	0.71	0.38	1.70
16	Jang et al. [56]	2012	β-Catenin	OS	0.41	0.19	0.85
				DFS	1.16	0.47	2.85
	Jang et al. [56]	2012	Cyclin D1	OS	0.205	0.09	0.46
				DFS	0.45	0.21	0.96
17	Chung et al. [59]	2001	β-Catenin, nuclear	OS	1.02	0.73	1.31
			β-Catenin, phosphonuclear	OS	2.18	1.30	3.68
18	Fernebro et al. [60]	2004	β-Catenin (cytoplasm)	OS	0.32	0.12	0.83
			β-Catenin (membrane)	OS	1.7	1.00	3.0
	Fernebro et al. [60]	2004	β-Catenin (nucleus)	OS	1.1	0.62	2.0
			p53	OS	1.1	0.50	2.5
19	Bondi et al. [61]	2004	β-Catenin (nuclear, combined with C-Myc)	OS	5.26	1.93	14.36
20	Jung et al. [64]	2013	β-Catenin	OS	0.68	0.39	1.19
			p53	OS	1.39	0.82	2.28
21	Wangefjord et al. [65]	2013	β-Catenin	Cancer-specific survival	0.70	0.51	0.97
22	Balzi et al. [66]	2015	β-Catenin (nucleus)	OS	1.99	0.75	5.32
				DFS	1.26	0.62	2.56
23	Togo et al. [68]	2008	β-Catenin	DFS	1.94	0.86	4.38
			p53	DFS	1.70	0.83	3.48
24	Matsuoka et al. [69]	2011	β-Catenin	OS	2.66	1.54	4.60
25	Morikawa et al. [70]	2011	β-Catenin (cytoplasm)	Cancer-specific mortality	0.82	0.64	1.06
			β-Catenin (nucleus)	Cancer-specific mortality	0.80	0.62	1.03
26	Stanzak et al. [72]	2011	β-Catenin	OS	2.48	1.30	4.74
27	Toth et al. [73]	2012	β-Catenin (membrane)	OS	0.58	0.14	2.28
			β-Catenin (nucleus)	OS	2.25	0.61	8.32
28	Horst et al. [98]	2009	β-Catenin	DFS	2.92	1.30	6.53
				Cancer-specific survival	7.46	2.08	26.72
29	Bazan et al. [27]	2005	TP53	OS	2.26	1.21	4.21
				DFS	2.14	1.06	4.32
30	Khan et al. [28]	2018	TP53	OS	0.88	0.78	1.00
			CTNNB1	OS	0.79	0.44	1.44
			SMAD-4	OS	1.31	1.09	1.57
			APC	OS	0.89	0.79	1.01
31	Brandstedt et al. [29]	2014	p53	CRC Risk	0.19	0.04	0.96
			β-Catenin	CRC risk	0.97	0.66	1.41
			Cyclin D1	CRC risk	0.07	0.01	0.88
32	Huemer et al. [30]	2018	TP53	OS	1.22	0.84	1.78
33	Sun et al. [31]	2014	TP53	OS	2.05	1.26	3.34
34	Warren et al. [33]	2013	TP53	OS	0.71	0.65	0.76
				DFS	0.60	0.54	0.66
35	Netter et al. [34]	2014	TP53	OS	0.99	0.53	1.55
				Progression-free survival	1.04	0.60	1.79
36	Loes et al. [51]	2016	TP53	Disease-specific survival	0.78	0.47	1.28
37	Kandioler et al. [35]	2015	TP53	OS	1.88	1.17	3.04
				CFS	1.73	1.04	2.86
38	Chen et al. [36]	2013	TP53	OS	1.58	0.97	2.56
				DFS	1.71	1.03	2.86
39	Oh et al. [38]	2019	TP53	5-year survival	2.71	1.60	4.60
40	Wang et al. [39]	2017	TP53	OS	0.47	0.27	0.83
				DFS	0.42	0.24	0.73
41	Zhang et al. [40]	2014	TP53	OS	1.66	0.88	3.14
				DFS	1.65	0.81	3.38
42	Chun et al. [42]	2019	TP53	OS	2.62	1.41	4.87
43	Tiong et al. [43]	2014	TP53 (and CTNNB1)	OS	1.50	1.05	2.14
			Wnt 5A	OS	1.93	1.17	3.19
44	Li et al. [44]	2018	TP53 (double mutation with PIK3CA)	OS	2.02	1.04	3.91
			TP53	OS	1.68	0.98	2.87
45	Morikawa et al. [46]	2012	TP53	Cancer-specific survival	1.30	1.02	1.65
46	Kawaguchi et al. [47]	2019	TP53	OS	2.21	1.49	3.28
				RFS	1.40	1.11	1.78
			SMAD-4	OS	1.82	1.17	2.83
				RFS	1.62	1.20	2.20
47	Samowitz et al. [48]	2002	TP53	OS	1.34	1.07	1.63
				Cancer-specific survival	1.10	0.91	1.34
48	Soong et al. [49]	2000	TP53	OS	1.40	0.89	2.21
49	Jurach et al. [50]	2006	TP53	OS	2.32	1.34	4.03
				Recurrence	2.64	1.19	5.83
50	Iacopetta et al. [45]	2006	TP53	OS	2.52	1.28	4.93
51	Iacopetta et al. [52]	2006	TP53	OS	0.61	0.50	0.73
52	Wangefjord et al. [26]	2011	Cyclin D1	Cancer-specific survival	0.69	0.49	0.96
53	Isaksson et al. [86]	2006	SMAD-4	OS	4.57	1.17	17.8
54	Tonescu et al. [93]	2014	SMAD-3	OS	1.09	0.30	3.99
55	Jia et al. [91]	2017	SMAD-4 (nuclear)	OS	1.70	0.96	3.00
			SMAD-4 (cytoplasm)	OS	1.39	0.76	2.56
56	Kim et al. [25]	2018	Wnt	OS	1.25	0.87	1.78
57	Veloudis et al. [24]	2017	Wnt/β-catenin	OS	3.86	1.24	11.9
58	Ting et al. [23]	2013	Wnt	OS	4.57	1.73	12.1
59	Yoshida et al. [22]	2015	Wnt	DFS	1.50	0.80	2.8
			β-Catenin	DFS	2.10	1.10	3.9
				OS	1.90	1.00	3.4
60	Rafael et al. [21]	2014	Wnt	OS	0.36	0.05	2.63
61	Bondi et al. [99]	2005	Cyclin D1	OS	0.57	0.33	0.98
62	Bahnassy et al. [100]	2004	Cyclin D1	OS	10.86	1.05	86.2
63	Saridaki et al. [101]	2010	Cyclin D1	OS	1.1	0.6	1.8
				RFS	0.8	0.5	1.4
64	Ogino et al. [102]	2009	Cyclin D1	OS	0.74	0.57	0.98
				CSS	0.57	0.39	0.84

The table represents 105 data points on genes where HR data were available. OS: overall survival, RFS: relapse-free survival, CFS: cancer-free survival, DFS: disease-free survival, PFS: progression-free survival, CRC risk: colorectal cancer risk.