Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer

Table 1 Allele frequencies and genotype distribution of GNAS1 T393C polymorphism in 122 gastric cancer patients and in the reference group (n = 820) n (%)

T393C	Patients (n = 122)			Reference group (n = 820)			χ2	P	Odds ratio	95% CI
Allele	C 135 (55.3)		T 109 (44.7)	C 873 (53.2)		T 767 (46.7)	0.38	0.54	0.92	0.70-1.20
Genotype	CC 39 (32.0)	CT 57 (46.7)	TT 26 (21.3)	CC 235 (28.7)	CT 403 (49.1)	TT 182 (22.2)	0.37	0.54	0.92

Table 2 Clinicopathological characteristics of 122 patients with gastric cancer n (%)

	All	T393C genotypes			P
		CC	CT	TT
n (%)	122 (100)	39 (32)	57 (46.7)	26 (21.3)
Gender
Male	78 (63.9)	25 (32.1)	34 (43.6)	19 (24.4)
Female	44 (36.1)	14 (31.8)	23 (52.3)	7 (15.9)	0.274
WHO
Papillary/Tubular/Mucinous	76 (62.3)	23 (30.3)	34 (44.7)	19 (25)
Signet-ring cancer	38 (31.1)	12 (31.6)	19 (50)	7 (18.4)
Other	8 (6.6)	4 (50)	4 (50)	0	0.340
Differentiation
Well/Moderate (G1-G2)	42 (34.4)	12 (28.6)	22 (52.4)	8 (19)
Poor (G3-G4)	80 (65.6)	27 (33.8)	35 (43.8)	18 (22.5)	0.805
Laurén
Intestinal	52 (42.6)	16 (30.8)	25 (48.1)	11 (21.2)
Diffuse	55 (45.1)	17 (30.9)	29 (52.7)	9 (16.4)
Mixed	15 (12.3)	6 (40)	3 (20)	6 (40)	0.171
Ming
Expanding	47 (38.5)	14 (29.8)	24 (51.1)	9 (19.1)
Infiltrative	75 (61.5)	25 (33.3)	33 (44)	17 (22.7)	0.620
pT-category
T1	30 (24.6)	7 (23.3)	13 (43.3)	10 (33.3)
T2	44 (36.1)	12 (27.3)	22 (50)	10 (22.7)
T3	38 (31.1)	14 (36.8)	18 (47.4)	6 (15.8)
T4	10 (8.2)	6 (60)	4 (40)	0	0.110
pN-category
N0	49 (40.2)	11 (22.4)	24 (49)	14 (28.6)
N1	34 (27.9)	13 (38.2)	13 (38.2)	8 (23.5)
N2	14 (11.5)	6 (42.9)	6 (42.9)	2 (14.3)
N3	25 (20.5)	9 (36)	14 (56)	2 (8)	0.196
pM-category
M0	99 (81.1)	30 (30.3)	45 (45.5)	24 (24.2)
M1	23 (18.9)	9 (39.1)	12 (52.2)	2 (8.7)	0.101
R-category
R0	118 (96.7)	38 (32.5)	54 (46.2)	25 (21.4)
R1/R2	4 (3.3)	1 (25)	2 (50)	1 (25)	0.950
UICC stage
Ia	26 (21.3)	5 (19.2)	11 (42.3)	10 (38.5)
Ib	22 (18)	7 (31.8)	12 (54.5)	3 (13.6)
II	18 (14.8)	4 (22.2)	7 (38.9)	7 (38.9)
IIIa	11 (9)	4 (36.4)	5 (45.5)	2 (18.2)
IIIb	4 (3.3)	2 (50)	2 (50)	0
IV	41 (33.6)	17 (41.5)	20 (48.8)	4 (9.8)	0.023

P values are given for dichotomization between C+ (CC+CT) and C- (TT) genotypes.

Table 3 Univariate and multivariate survival analysis of 122 gastric cancer patients

Covariate	n	Univariate analysis			Multivariate analysis
		P value	5-yr-SR (%)	SE (±%)	P value	HR	95% CI
pT-category		< 0.001			< 0.001
pT1	30		85.4	6.8		1
pT2	44		44.5	7.8	< 0.001	6.212	2.31-16.70
pT3	38		5.4	3.7	< 0.001	13.026	4.44-38.23
pT4	10		33.3	15.7	0.001	7.838	2.24-27.46
pN-category		< 0.001			0.549
pN0	49		61.6	7.4		1
pN1	34		47.1	8.6	0.226	0.663	0.34-1.29
pN2	14		16.9	10.9	0.986	0.993	0.43-2.27
pN3	25		8.0	5.4	0.814	0.905	0.40-2.07
T393C SNP		0.043			0.333
CC/CT	96		36.7	5.1		1
TT	26		56.9	10.4		0.712	0.36-1.42
pM-category		< 0.001			0.027
M0	99		48.1	5.2		1
M1	23		9.2	6.2		2.087	1.09-4.01
R-category		< 0.001			0.022
R0	118		42.3	4.7		1
R+	4		0	0		3.128	1.18-8.27

SNP: Single nucleotide polymorphism; 5-yr-SR: 5-yr-survival; HR: Hazard ratio.

Table 4 Summary of the effect of the GNAS1 T393C polymorphism on various carcinomas

Cancer type	Yr	n	Effect	Benefit (survival)
Gastric cancer	2009	122	The present study demonstrates a significant survival benefit for the TT genotype with a 5-yr-survival rate of 56.9% vs the CC/CT group with a 5-yr-survival rate of only 36.7% (P = 0.043)	TT-genotype
Squamous cell cancer of larynx[15]	2008	157	Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III-IV) with higher 5-yr survival rates for TT, followed by TC and CC (P = 0.0437)	TT-genotype
Oro- and hypo-pharyngeal squamous cell carcinoma[16]	2008	202	C homozygous patients displayed a higher risk for disease progression than T homozygous patients (P = 0.019) and a higher risk for death (P = 0.015). In multivariate analysis, besides cancer stage and tumor localization, the T393C polymorphism was an independent prognostic factor for disease progression and death	TT-genotype
Clear cell renal cell carcinoma[11]	2006	150	Tumor progression, development of metastasis and tumor-related death was significantly associated with the T393C polymorphism. In multivariate analysis CC patients were at highest risk for progression or tumor-related death compared with T-allele carriers (P = 0.018)	TT-genotype
Chronic lymphocytic leukemia[17]	2006	144	Median progression-free survival was significantly higher for T-allele carriers (P = 0.007). In multivariate analysis, the T393C polymorphism kept its prognostic independence (P = 0.01) besides of ZAP-70 (P = 0.005) and Binet stage (P < 0.001). Regarding overall survival, CC genotypes were significantly at highest risk for death compared to T-alleles both in univariate (P < 0.001) and multivariate analysis (P = 0.002)	TT-genotype
Bladder cancer[10]	2005	254	Progression-free survival (P = 0.011), metastasis-free survival (P = 0.001) and cancer-specific survival (P = 0.014) were significantly increased in TT genotypes compared with CC genotypes. In multivariate analysis, the T393C polymorphism kept its prognostic independence	TT-genotype
Sporadic colorectal cancer[12]	2005	151	In UICC stages I to II, the 5-yr survival rate was significantly (P = 0.009) higher in TT genotypes (88%) compared with TC (71%) and CC genotypes (50%). In multivariate analysis, the T393C polymorphism was also an independent prognostic factor. No significant effect could be seen for UICC stages III to IV	TT-genotype
Cholangio-carcinoma[14]	2007	87	Disease-specific overall survival was significantly dependent on the T393C genotype (P = 0.02), with TT genotypes showing reduced survival compared to patients carrying at least one C allele. In multivariate analysis (TT/C+) the T393C genotype kept its prognostic independence (P = 0.04)	CC-genotype
Breast carcinoma[13]	2007	279	Overall survival was significantly (P = 0.033) associated with the T393C polymorphism with lowest survival rates for the TT-genotype and highest survival rate for the CC-genotype. In multivariate analysis, the TT-genotype still had a significant survival benefit compared to the CC genotype (P = 0.045)	CC-genotype
Esophageal cancer[28]	2009	51	T393C polymorphism was significantly associated with tumor response to Cisplatin/5-FU-based radiochemotherapy. 63% of the T allele carriers had a minor histopathologic response (MiHR) with more than 10% residual vital tumor cells in resection specimens. For the CC genotype MiHR was seen only in 20%. In binary logistic regression analysis, the T393C genotype kept its independence (P < 0.05)	CC-genotype