Table 3. Associations between SNPs of MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes and cancers of the esophagus, stomach, and liver –the comparison between results from single SNP model1 and joint SNPs model2.
| Esophageal Cancer | Stomach Cancer | Liver Cancer | |||||||||||||
| Ca/Co | SBOR1 (95% posterior limit) | One-sidedP * | SBOR2 (95% posterior limit) | One-sidedP * | Ca/Co | SBOR1 (95% posterior limit) | One-sided P * | SBOR2 (95% posterior limit) | One- sided P * | Ca/Co | SBOR1 (95% posterior limit) | One- sided P * | SBOR2 (95% posterior limit) | One- sided P * | |
| MTHFR | |||||||||||||||
| rs1801133 | |||||||||||||||
| CC | 65/135 | 1.00 | 1.00 | 50/135 | 1.00 | 1.00 | 50/135 | 1.00 | 1.00 | ||||||
| CT | 105/199 | 1.19 (0.80, 1.77) | 0.20 | 1.20 (0.73, 1.96) | 0.24 | 106/199 | 1.53 (1.00, 2.33) | 0.024 | 1.33 (0.79, 2.21) | 0.14 | 114/199 | 1.57 (1.02, 2.42) | 0.021 | 1.34 (0.80, 2.25) | 0.14 |
| TT | 32/57 | 1.35 (0.78, 2.32) | 0.14 | 1.72 (0.91, 3.27) | 0.048 | 38/57 | 2.26 (1.30, 3.91) | 0.002 | 2.15 (1.13, 4.08) | 0.010 | 30/57 | 1.17 (0.64, 2.12) | 0.31 | 1.07 (0.52, 2.20) | 0.42 |
| P trend † | 0.21 | 0.033 | 0.001 | 0.003 | 0.24 | 0.18 | |||||||||
| Dominant | 1.25 (0.85, 1.84) | 0.13 | 1.37 (0.85, 2.21) | 0.10 | 1.79 (1.18, 2.71) | 0.003 | 1.64 (1.01, 2.66) | 0.022 | 1.51 (0.98, 2.32) | 0.029 | 1.40 (0.88, 2.24) | 0.078 | |||
| Recessive | 1.23 (0.74, 2.03) | 0.21 | 1.55 (0.87, 2.75) | 0.069 | 1.78 (1.09, 2.91) | 0.011 | 1.93 (1.11, 3.35) | 0.009 | 0.91 (0.53, 1.56) | 0.37 | 1.00 (0.54, 1.83) | 0.49 | |||
| MTR | |||||||||||||||
| rs1805087 | |||||||||||||||
| A/A | 161/310 | 1.00 | 1.00 | 142/310 | 1.00 | 1.00 | 149/310 | 1.00 | 1.00 | ||||||
| A/G | 35/76 | 0.79 (0.50, 1.27) | 0.17 | 0.83 (0.48, 1.45) | 0.26 | 46/76 | 1.16 (0.74, 1.83) | 0.26 | 1.23 (0.73, 2.09) | 0.22 | 40/76 | 0.92 (0.57, 1.47) | 0.36 | 0.94 (0.54, 1.63) | 0.41 |
| G/G | 4/0 | – | – | 1/0 | – | – | 1/0 | – | – | ||||||
| Dominant | 0.90 (0.57, 1.42) | 0.32 | 0.94 (0.55, 1.62) | 0.42 | 1.19 (0.76, 1.87) | 0.22 | 1.30 (0.78, 2.15) | 0.16 | 0.93 (0.58, 1.49) | 0.38 | 1.20 (0.73, 1.98) | 0.23 | |||
| MTRR | |||||||||||||||
| rs1532268 | |||||||||||||||
| C/C | 145/283 | 1.00 | 1.00 | 144/283 | 1.00 | 1.00 | 149/283 | 1.00 | 1.00 | ||||||
| C/T | 47/94 | 1.16 (0.76, 1.78) | 0.25 | 0.99 (0.57, 1.70) | 0.48 | 44/94 | 0.98 (0.63, 1.53) | 0.47 | 1.01 (0.58, 1.77) | 0.48 | 39/94 | 0.83 (0.52, 1.32) | 0.21 | 1.03 (0.59, 1.81) | 0.46 |
| T/T | 11/11 | 1.96 (0.89, 4.31) | 0.047 | 1.61 (0.61, 4.25) | 0.17 | 5/11 | 1.05 (0.43, 2.57) | 0.46 | 0.83 (0.25, 2.70) | 0.38 | 4/11 | 1.09 (0.42, 2.82) | 0.43 | 1.58 (0.54, 4.63) | 0.20 |
| P trend † | 0.070 | 0.21 | 0.97 | 0.49 | 0.61 | 0.50 | |||||||||
| Dominant | 1.32 (0.88, 1.98) | 0.089 | 1.12 (0.67, 1.87) | 0.34 | 1.00 (0.65, 1.52) | 0.49 | 1.06 (0.63, 1.80) | 0.41 | 0.85 (0.54, 1.34) | 0.25 | 0.97 (0.59, 1.60) | 0.46 | |||
| Recessive | 1.91 (0.87, 4.19) | 0.052 | 1.70 (0.66, 4.40) | 0.14 | 1.06 (0.43, 2.57) | 0.45 | 0.87 (0.27, 2.81) | 0.41 | 1.12 (0.43, 2.90) | 0.41 | 1.41 (0.51, 3.86) | 0.25 | |||
| rs1801394 | |||||||||||||||
| A/A | 117/204 | 1.00 | 1.00 | 119/204 | 1.00 | 1.00 | 114/204 | 1.00 | 1.00 | ||||||
| A/G | 74/149 | 0.92 (0.63, 1.35) | 0.34 | 0.84 (0.51, 1.36) | 0.24 | 63/149 | 0.74 (0.49, 1.11) | 0.070 | 0.66 (0.40, 1.08) | 0.049 | 64/149 | 0.74 (0.49, 1.12) | 0.078 | 0.79 (0.47, 1.31) | 0.18 |
| G/G | 10/25 | 0.95 (0.47, 1.93) | 0.44 | 1.16 (0.52, 2.59) | 0.36 | 9/25 | 0.77 (0.37, 1.60) | 0.24 | 0.98 (0.41, 2.34) | 0.49 | 13/25 | 1.39 (0.70, 2.78) | 0.17 | 1.60 (0.72, 3.55) | 0.12 |
| P trend † | 0.70 | 0.50 | 0.13 | 0.075 | 0.87 | 0.33 | |||||||||
| Dominant | 0.92 (0.64, 1.34) | 0.33 | 0.89 (0.56, 1.43) | 0.32 | 0.73 (0.49, 1.07) | 0.055 | 0.65 (0.41, 1.03) | 0.034 | 0.83 (0.56, 1.24) | 0.19 | 0.95 (0.61, 1.49) | 0.42 | |||
| Recessive | 0.97 (0.48, 1.96) | 0.47 | 1.35 (0.62, 2.92) | 0.23 | 0.84 (0.41, 1.74) | 0.32 | 1.09 (0.48, 2.47) | 0.42 | 1.53 (0.78, 3.03) | 0.11 | 1.49 (0.71, 3.13) | 0.14 | |||
| DNMT1 | |||||||||||||||
| rs2228612 | |||||||||||||||
| A/A | 52/100 | 1.00 | 1.00 | 43/100 | 1.00 | 1.00 | 48/100 | 1.00 | 1.00 | ||||||
| A/G | 56/200 | 0.52 (0.33, 0.82) | 0.003 | 0.52 (0.31, 0.85) | 0.005 | 72/200 | 0.82 (0.51, 1.31) | 0.20 | 0.81 (0.48, 1.36) | 0.21 | 74/200 | 0.79 (0.49, 1.28) | 0.17 | 0.69 (0.40, 1.18) | 0.088 |
| G/G | 29/57 | 0.96 (0.55, 1.68) | 0.44 | 0.87 (0.47, 1.58) | 0.32 | 28/57 | 1.12 (0.62, 2.04) | 0.35 | 1.06 (0.55, 2.04) | 0.43 | 36/57 | 1.35 (0.76, 2.42) | 0.15 | 1.25 (0.66, 2.35) | 0.25 |
| P trend † | 0.37 | 0.12 | 0.88 | 0.48 | 0.42 | 0.32 | |||||||||
| Dominant | 0.60 (0.39, 0.94) | 0.012 | 0.58 (0.36, 0.94) | 0.013 | 0.89 (0.56, 1.41) | 0.31 | 0.90 (0.55, 1.48) | 0.34 | 0.93 (0.58, 1.50) | 0.39 | 0.82 (0.51, 1.32) | 0.21 | |||
| Recessive | 1.35 (0.81, 2.25) | 0.13 | 1.20 (0.69, 2.09) | 0.25 | 1.26 (0.74, 2.15) | 0.20 | 1.19 (0.69, 2.07) | 0.26 | 1.54 (0.92, 2.59) | 0.051 | 1.62 (0.97, 2.71) | 0.033 | |||
| ALDH2 | |||||||||||||||
| rs671 | |||||||||||||||
| G/G | 118/213 | 1.00 | 1.00 | 108/213 | 1.00 | 1.00 | 109/213 | 1.00 | 1.00 | ||||||
| A/G | 60/160 | 0.76 (0.51, 1.13) | 0.088 | 0.78 (0.48, 1.27) | 0.16 | 76/160 | 1.06 (0.71, 1.57) | 0.39 | 0.99 (0.61, 1.62) | 0.49 | 74/160 | 1.05 (0.70, 1.58) | 0.41 | 1.04 (0.63, 1.70) | 0.44 |
| A/A | 25/20 | 1.61 (0.86, 3.00) | 0.066 | 1.10 (0.52, 2.31) | 0.40 | 12/20 | 0.99 (0.48, 2.03) | 0.49 | 1.12 (0.51, 2.47) | 0.39 | 10/20 | 0.96 (0.45, 2.06) | 0.46 | 0.80 (0.34, 1.92) | 0.31 |
| P trend † | 0.67 | 0.31 | 0.88 | 0.49 | 0.94 | 0.33 | |||||||||
| Dominant | 0.90 (0.62, 1.31) | 0.29 | 0.80 (0.51, 1.26) | 0.17 | 1.05 (0.71, 1.54) | 0.41 | 1.00 (0.63, 1.58) | 0.50 | 1.04 (0.70, 1.54) | 0.43 | 0.94 (0.61, 1.47) | 0.40 | |||
| Recessive | 1.76 (0.96, 3.24) | 0.035 | 1.16 (0.56, 2.37) | 0.35 | 0.97 (0.48, 1.97) | 0.47 | 1.01 (0.48, 2.14) | 0.49 | 0.95 (0.45, 2.01) | 0.44 | 0.84 (0.37, 1.87) | 0.33 | |||
| rs2238151 | |||||||||||||||
| C/C | 173/293 | 1.00 | 1.00 | 151/293 | 1.00 | 1.00 | 166/293 | 1.00 | 1.00 | ||||||
| C/T | 11/34 | 0.66 (0.34, 1.29) | 0.11 | 0.81 (0.35, 1.86) | 0.31 | 18/34 | 1.21 (0.65, 2.23) | 0.28 | 1.00 (0.45, 2.22) | 0.50 | 7/34 | 0.51 (0.23, 1.11) | 0.045 | 0.36 (0.14, 0.92) | 0.016 |
| T/T | 0/1 | – | – | 0/1 | – | 1/1 | 1.43 (0.39, 5.33) | 0.30 | 1.00 (0.25, 4.00) | 0.50 | |||||
| P trend † | – | – | – | 0.29 | 0.006 | ||||||||||
| Dominant | 0.65 (0.33, 1.28) | 0.11 | 0.80 (0.35, 1.84) | 0.30 | 1.20 (0.65, 2.21) | 0.29 | 1.08 (0.49, 2.35) | 0.43 | 0.58 (0.27, 1.25) | 0.082 | 0.31 (0.13, 0.75) | 0.005 | |||
| Recessive | – | – | – | 1.44 (0.39, 5.37) | 0.29 | 1.00 (0.25, 4.00) | 0.50 | ||||||||
| rs886205 | |||||||||||||||
| G/G | 173/315 | 1.00 | 1.00 | 150/315 | 1.00 | 1.00 | 149/315 | 1.00 | 1.00 | ||||||
| A/G | 29/69 | 0.78 (0.48, 1.28) | 0.17 | 1.05 (0.55, 2.00) | 0.44 | 41/69 | 1.47 (0.92, 2.34) | 0.054 | 1.76 (0.93, 3.33) | 0.041 | 40/69 | 1.38 (0.85, 2.24) | 0.096 | 1.41 (0.75, 2.66) | 0.14 |
| A/A | 2/4 | 1.00 (0.33, 3.08) | 0.50 | 0.82 (0.25, 2.69) | 0.37 | 2/4 | 1.18 (0.39, 3.65) | 0.38 | 0.65 (0.19, 2.23) | 0.25 | 2/4 | 1.27 (0.40, 4.10) | 0.34 | 1.07 (0.31, 3.76) | 0.46 |
| P trend † | 0.39 | 0.37 | 0.098 | 0.31 | 0.14 | 0.17 | |||||||||
| Dominant | 0.79 (0.49, 1.29) | 0.17 | 0.99 (0.52, 1.86) | 0.48 | 1.48 (0.93, 2.34) | 0.047 | 1.38 (0.76, 2.51) | 0.15 | 1.41 (0.88, 2.28) | 0.076 | 1.34 (0.76, 2.37) | 0.16 | |||
| Recessive | 1.02 (0.33, 3.13) | 0.49 | 0.85 (0.26, 2.75) | 0.39 | 1.16 (0.38, 3.55) | 0.40 | 0.70 (0.20, 2.40) | 0.28 | 1.25 (0.39, 4.03) | 0.35 | 0.93 (0.28, 3.04) | 0.45 | |||
1
: Single SNP model: models included one SNP only; Semi-Bayes odds ratio (SBOR) adjusted for age (5-year categories and deviation from stratum mean), sex, residency (city, rural), alcohol drinking frequency, smoking pack-years, BMI, education, H. pylori infection (in stomach cancer analyses), HBsAg (in liver cancer analyses), and plasma AFB1 levels (in liver cancer analyses), based on the assumption that genotype did not affect any of these variables.
2
: Joint SNPs model: models included all of the 8 SNPs; SBOR adjusted for the same set of covariates. All of the SNPs combined together were under the same genetic models (genotype-specific, log-additive, dominant, or recessive).
*: One-sided semi-Bayes P-values; the posterior probability that the point estimate is on the wrong side of the null [26], [27].
†
: P-value from Chi-Square test for trend.