Genetic variations in the SMAD4 gene and gastric cancer susceptibility

Table 1 Information on five genotyped tagging single nucleotide polymorphisms in the SMAD4 gene

SNP No.	SNP ID	Location	MAF			P2	P for HWE3	Genotyping rate (%)
			Database1	Cases	Controls
1	rs12958604	Intron 2	0.446	0.452	0.450	0.956	0.893	99.1
2	rs10502913	Intron 2	0.363	0.280	0.305	0.308	0.117	99.4
3	rs17663887	Intron 9	0.056	0.023	0.057	< 0.001	0.258	100.0
4	rs9304407	Intron 11	0.411	0.458	0.423	0.206	0.291	100.0
5	rs12456284	3’-UTR	0.405	0.289	0.350	0.017	0.231	100.0

¹Minor allele frequency (MAF) for Han Chinese in Beijing (CHB) population in the HapMap database (http://www.hapmap.org);

²P value for the allele distribution difference between the cases and controls;

³Hardy-Weinberg equilibrium (HWE) P value in the control group. SNP: Single nucleotide polymorphism; 3’-UTR: 3’-untranslated region.

Table 2 Frequency distributions of selected variables between gastric cancer cases and cancer-free controls n (%)

Variables	Cases (n = 322)	Controls (n = 351)	P1
Age (yr)
< 60	129 (40.1)	153 (43.6)	0.354
≥ 60	193 (59.9)	198 (56.4)
Sex
Male	215 (66.8)	226 (64.4)	0.516
Female	107 (33.2)	125 (35.6)
Smoking status
Never	181 (56.2)	228 (65.0)	0.020
Regular	141 (43.8)	123 (35.0)
Drinking status
Never	217 (67.4)	239 (68.1)	0.846
Regular	105 (32.6)	112 (31.9)
Tumor site2
Cardia	149 (48.1)
Non-cardia	161 (51.9)
Histological types2
Intestinal	162 (52.3)
Diffuse	148 (47.7)
Depth of tumor infiltration2
T1	80 (25.8)
T2	68 (22.0)
T3	112 (36.1)
T4	50 (16.1)
Lymph node metastasis2
Negative	166 (52.9)
Positive	148 (47.1)

¹Two-sided χ² test for the frequency distribution of selected variables between gastric cancer cases and cancer-free controls;

²No. of subjects in cases (n = 310 for tumor site, n = 310 for histological types, n = 310 for depth of tumor infiltration, and n = 314 for lymph node metastasis) were less than the total number (n = 322) because some information was not obtained.

Table 3 Genotype distributions of the SMAD4 tSNPs in gastric cancer cases and controls and risk estimates n (%)

SNP No.	SNP ID	Genotypes	Cases (n = 322)	Controls (n = 351)1	P value (2df)2	Crude OR (95% CI)	Adjusted OR (95% CI)3
1	rs12958604	AA	99 (30.8)	106 (30.5)	0.961	1.00	1.00
		AG	155 (48.1)	171 (49.1)		0.97 (0.68-1.38)	0.98 (0.69-1.39)
		GG	68 (21.1)	71 (20.4)		1.03 (0.67-1.59)	1.01 (0.66-1.56)
2	rs10502913	GG	164 (51.0)	162 (46.4)	0.505	1.00	1.00
		GA	136 (42.2)	161 (46.1)		0.83 (0.61-1.14)	0.86 (0.63-1.18)
		AA	22 (6.8)	26 (7.5)		0.84 (0.46-1.54)	0.81 (0.44-1.49)
3	rs17663887	TT	307 (95.3)	311 (88.6)	< 0.001	1.00	1.00
		TC	15 (4.7)	40 (11.4)		0.38 (0.21-0.70)	0.38 (0.21-0.71)
4	rs9304407	GG	85 (26.4)	112 (31.9)	0.291	1.00	1.00
		GC	179 (55.6)	181 (51.6)		1.30 (0.92-1.85)	1.32 (0.93-1.87)
		CC	58 (18.0)	58 (16.5)		1.32 (0.83-2.09)	1.29 (0.81-2.05)
5	rs12456284	AA	149 (46.3)	143 (40.7)	0.003	1.00	1.00
		AG	160 (49.7)	170 (48.4)		0.90 (0.66-1.24)	0.90 (0.66-1.24)
		GG	13 (4.0)	38 (10.8)		0.33 (0.17-0.64)	0.31 (0.16-0.60)

¹No. of subjects in controls (n = 348 for SNP1, n = 349 for SNP2) were less than the total number (n = 351) because some DNA could not be genotyped;

²Two-sided χ² test for the frequency distribution;

³Adjusted for age, sex, smoking status, and alcohol use. SNP: Single nucleotide polymorphism; OR: Odds ratio; CI: Confidence interval.

Table 4 Frequency distributions of the combined genotypes of SMAD4 SNP3 and SNP5 between gastric cancers and controls n (%)

No. variant (protective) alleles of the combined genotypes1	Cases (n = 322)	Controls (n = 351)	P2	Adjusted OR (95% CI)3
0	138 (42.9)	127 (36.2)	< 0.001
1	167 (51.8)	166 (42.3)
2	17 (5.3)	54 (15.4)
3	0 (0.0)	4 (1.1)
Dichotomized groups
0-1	305 (94.7)	293 (83.5)	< 0.001	1.00
2-3	17 (5.3)	58 (16.5)		0.28 (0.16–0.49)

¹0-3 represent the number of variants within the combined genotypes (0 = no variant and 1-3 = 1-3 variants); the variant (protective) alleles used for the calculation were the SNP3 C and SNP5 G alleles;

²Two-sided χ² test for the frequency distribution;

³Odds ratios (ORs) were obtained from a logistic regression model with adjustment for age, sex, smoking status, and alcohol use. SNP: Single nucleotide polymorphism; CI: Confidence interval.