Of the 280 cases and 330 controls enrolled in the case and control groups, ADH7 genotyping was performed successfully in 250 of 280 participants in the case group and in 322 of 330 participants in the control group. We conducted a case-control study involving those participants with successful genotyping.
Characteristics of the participants
The average age of the case group was 62.2 (28–86 years) and 43.8 (21–76 years) in the control group, showing a higher average age in the case group than in the control group (P<0.001). There were 219 males and 31 females in the case group and 305 males and 17 females in the control group. Significantly more heavy drinkers were found in the case group compared to the control group (P<0.001). By primary sites of HNSCC, there were 120 patients with laryngeal cancer, 64 patients with oral cavity cancer, 31 patients with oropharyngeal cancer and, 35 patients with hypopharyngeal cancer.
ADH7 allele frequency
The allele frequencies of ADH7 rs1573496C>G, rs3737482T>C, rs1154460G>A, and rs284787T>C were examined (Table 2). All genetic polymorphisms fit the Hardy-Weinberg equilibrium.
ADH7 polymorphism and risk of head and neck squamous cell carcinoma
In ADH7 rs1573496C>G, the frequencies were 100% only in the CC genotype in the case group, and the frequencies of CC, CG, and GG genotypes were 99.7%, 0.3%, and 0%, respectively, in the control group. The odds ratio was undetermined (Table 3).
In ADH7 rs3737482T>C, the frequencies of the three genotypes TT, CT, and CC were 37.2%, 44.4%, 18.4%, respectively, in the case group and 25.2%, 52.5%, 22.4% in the control group, respectively (Table 3). Based on the TT genotype, the OR of the CT genotype was 0.48(95% CI: 0.29–0.78), and the OR of the CC genotype was 0.69(95% CI: 0.49–0.96), showing significantly low odds ratios in both genotypes.
In ADH7 rs1154460G>A, the frequencies of the three genotypes GG, AG, and AA were 37.6%, 48.0%, 14.4%, respectively, in the case group and 42.2%, 48.8%, 9.0%, respectively, in the control group (Table 3). Based on the GG genotype, the OR of the AG genotype was 1.47(95% CI: 1.06–2.04) and 2.03(95% CI: 1.05–3.92), in the co-dominant and recessive models, respectively, while the OR of the AA genotype was 1.63(95% CI: 1.11–2.40) in the referent model, showing a significantly higher odds ratio in the AA genotype.
In ADH7 rs284787T>C, the frequencies of the three genotypes TT, CT, and CC were 40.4%, 47.2%, 12.4%, respectively, in the case group and 45.7%, 42.2%, 12.1%, respectively, in the control group (Table 3). Based on the TT genotype, the OR of the CT genotype was 1.43(95% CI: 0.90–2.28), and the CC genotype was 1.24(95% CI: 0.87–1.74). Neither genotype showed statistically significant differences.
Linkage disequilibrium and haplotype of ADH7
In the analysis of ADH7 linkage disequilibrium, high linkage disequilibrium occurred only between rs3737482T>C and rs1154460G>A (Figure 1). Three types of haplotype were found showing more than 5% of frequency observed in ADH7 rs3737482T>C and rs1154460G>A. Of the 3 haplotypes, ADH7-ht1 and ADH7-ht2 were excluded from the analysis as they were almost identical, with rs3737482T>C and rs1154460G>A, respectively. The ADH7-ht3 haplotype (T allele in rs3737482 and G allele in rs1154460) was analyzed.
In the genetic analysis of ADH7 ht3, the ht3 -/- group was 62.0% in the case group and 67.1% in the control group. The ht3 +/- group was 34.0% in the case group and 29.8% in the control group. The ht3 +/+ group was 4.0% in the case group and 3.1% in the control group. Based on the ht3 -/- group, the OR of the ht3 +/- group was 1.22(95% CI: 0.77–1.93) and 0.99(95% CI: 0.55–1.78) in the ht3 +/+ group, and no statistically significant difference was found (Table 4).
ADH7 rs3737482T>C and rs1154460G>A and risk of head and neck squamous cell carcinoma according to alcohol consumption
The relative risk of HNSCC was analyzed in ADH7 rs3737482T>C and rs1154460G>A, according to alcohol drinking history. In ADH7 rs3737482T>C, based on the TT genotype, the OR was 0.43 (95% CI: 0.42–0.77) in the CT genotype and 0.42 (95% CI: 0.19–0.94) in the CT genotype in the drinker group, indicating a significant decrease. In ADH7 rs1154460G>A, based on the GG genotype, the OR of the AA genotype were 3.55 (95% CI: 1.51–8.33) in the drinker group, indicating a significant increase (Table 5). The analysis was also performed by dividing the drinker group into social drinkers and heavy drinkers. In ADH7 rs3737482T>C, based on the TT genotype, the OR was 0.16 (95% CI: 0.04–0.69) in the CC genotype in the social drinker group and 0.40 (95% CI: 0.17–0.92) in the CT genotype in the heavy-drinker group. In ADH7 rs1154460G>A, based on the GG genotype, the OR of the AG genotype and the AA genotype were 2.60 (95% CI: 1.02–6.62) and 5.85 (95% CI: 1.58–21.62) in the social drinker group.