The data in Table 3 (at the end of the manuscript) showed the general information of all subjects of 505 GCs and 544 HCs. The mean age was 59.08 (59.08 ± 10.55 years) in GC group and 58.33 (58.33 ± 11.55 years) in the HCs. According to the 7th Edition of the American Joint Committee on Cancer (AJCC) , 87 cases (17.2%), 156 cases (30.9%), 128 cases (25.3%), 65 cases (12.9%) and 69 cases (13.7%) were classified as TNM I, II, III, IV and other stages, respectively. The number of subjects with a history of GC, no family history of cancer, and other cancers were 398 (78.8%), 42 (8.3%) and 65 (12.9%), respectively. There was no significant difference in age or gender between the two groups (P = 0.105 and P = 0.404), indicating no sample matching bias between groups. However, there was a significant difference in smoking status, pack-years and drinking status between the two groups (P < 0.0001).
Distribution of the genotypic and allelic frequencies of DAL-1 polymorphisms and their association with GC susceptibility
The genotypic frequencies of six SNPs except rs7240736 of the controls were all in accordance with Hardy–Weinberg equilibrium (P > 0.05). Hence the rs7240736 was eliminated in the next analysis. The genotypic distributions of the other five SNPs among the cases and controls and their associations with GC risk are summarized in Additional file 1: Table S1. All the allelic frequencies were not significantly different between the GCs and HCs. There was no evident association between the five SNPs with GC risk in the homozygotes, heterozygotes or two genetic models (dominant genetic model and recessive genetic model) after adjusting for age, gender, smoking status, pack-years, and drinking status (P > 0.05). The above comparisons were all not statistically significant by using multiple test correction.
Haplotype analysis and GC risk
No strong LD for the selected SNPs of the DAL-1 were identified by the Haploview software (Fig. 1). One LD block was found in the DAL-1 gene, which contained five haplotypes in the block. The associations between haplotype frequencies and GC risk were shown in Additional file 1: Table S2. The most common haplotypes within this block were determined as GTTC (0.777), ACTC (0.074), GTCC (0.068), followed by GTTG (0.044), and ATTC (0.020). No apparent association between each haplotype and GC risk within this block was observed.
Stratified analysis between DAL-1 polymorphisms and GC risk
We conducted stratified analyses for all candidate SNPs according to age, gender, smoking status, pack-years, and drinking status, which were reported to have potential influences on GC occurence. As was shown in Table 4 (at the end of the manuscript), the TA + AA genotypes of rs9953490 were associated with a significantly higher GC risk in smoker than nonsmoker before adjustment by age, gender, smoking status, pack-years, and drinking status (TA + AA vs TT, OR = 2.33, 95% CI = 1.11–4.87, P = 0.025). However, this significant association was compromised after adjustment by age, gender, smoking status, pack-years, and drinking status (TA + AA vs TT, adjusted OR = 1.62, 95% CI = 0.61–4.27, P = 0.333). Meanwhile, for other SNPs, no significant association was found between genotypes and GC risk in the stratified analyses (Additional file 1: Tables S3–S7).
We further conducted stratified analyses in 274 patients with available clinicopathological information such as family history of cancer, tumor size, neoplasia location, depth of invasion, lymph metastasis, TNM stage, and Lauren’s classification. As shown in Table 5 (at the end of the manuscript), the TA + AA genotypes of rs9953490 were significantly associated with increased GC risk in N3 compared with N0 (TA + AA vs TT adjusted OR = 4.56, 95% CI = 1.49–13.98, P = 0.008), and with a obviously increased GC risk in TNM stage III compared with stage I-II (TA + AA vs TT adjusted OR = 2.33, 95% CI = 1.16–4.67, P = 0.017). No associations were found between other SNPs and the clinicopathological characteristics of GC (Additional file 1: Tables S8–S12). The above comparisons showed no statistical significance using multiple test correction analysis.
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