Table 3.
Association between one-carbon metabolism polymorphisms and diet and CIMP in colon tumors, case-control comparisona,b
| Polymorphismc and exposure | Tertiled | Controls |
CIMP− (zero or one marker methylated) |
CIMP+ (two or more of five markers methylated) |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| wt |
Het/Var |
wt |
Het/Var |
Pe | wt |
Het/Var |
Pe | ||||||||||
| N | N | N | OR | 95% CI | N | OR | 95% CI | N | OR | 95% CI | N | OR | 95% CI | ||||
| MTHFR 677C > T | |||||||||||||||||
| Folate | Low | 281 | 362 | 115 | 1.0 | — | 136 | 0.9 | (0.6, 1.2) | 53 | 1.0 | — | 52 | 0.8 | (0.5, 1.2) | ||
| Middle | 324 | 339 | 106 | 0.8 | (0.6, 1.2) | 119 | 0.8 | (0.6, 1.1) | 35 | 0.5 | (0.3, 0.9) | 44 | 0.7 | (0.5, 1.1) | |||
| High | 280 | 384 | 89 | 0.7 | (0.5, 1.1) | 89 | 0.5 | (0.4, 0.7) | ns | 33 | 0.5 | (0.4, 0.9) | 43 | 0.6 | (0.4, 0.9) | ns | |
| Alcoholf (long term) | None | 350 | 404 | 114 | 1.0 | — | 126 | 0.9 | (0.6, 1.2) | 42 | 1.0 | — | 64 | 1.4 | (0.9, 2.2) | ||
| Moderate | 339 | 453 | 120 | 1.0 | (0.7, 1.4) | 135 | 0.8 | (0.6, 1.1) | 48 | 1.2 | (0.8, 1.9) | 43 | 0.9 | (0.6, 1.5) | |||
| High | 194 | 227 | 76 | 1.0 | (0.7, 1.5) | 83 | 0.9 | (0.6, 1.3) | ns | 31 | 1.2 | (0.7, 1.9) | 32 | 1.2 | (0.7, 1.9) | ns | |
| MTHFR 1298A > C | |||||||||||||||||
| Folate | Low | 304 | 339 | 126 | 1.0 | — | 125 | 0.9 | (0.6, 1.1) | 42 | 1.0 | — | 63 | 1.4 | (0.9, 2.2) | ||
| Middle | 317 | 346 | 110 | 0.8 | (0.6, 1.1) | 115 | 0.8 | (0.6, 1.04) | 32 | 0.7 | (0.4, 1.1) | 47 | 1.0 | (0.6, 1.5) | |||
| High | 308 | 356 | 90 | 0.7 | (0.5, 1.0) | 88 | 0.5 | (0.4, 0.8) | ns | 34 | 0.7 | (0.5, 1.2) | 42 | 0.8 | (0.5, 1.2) | ns | |
| Alcoholf (long term) | None | 337 | 417 | 117 | 1.0 | — | 123 | 0.8 | (0.6, 1.1) | 56 | 1.0 | — | 50 | 0.7 | (0.5, 1.2) | ||
| Moderate | 387 | 405 | 124 | 0.9 | (0.6, 1.2) | 131 | 0.8 | (0.6, 1.1) | 32 | 0.5 | (0.3, 0.9) | 59 | 1.0 | (0.6, 1.5) | |||
| High | 203 | 218 | 85 | 1.0 | (0.7, 1.4) | 74 | 0.8 | (0.5, 1.1) | ns | 20 | 0.5 | (0.3, 0.97) | 43 | 1.1 | (0.7, 1.8) | <0.01 | |
| ADH3 I349V *1/*2 | |||||||||||||||||
| Folate | Low | 243 | 399 | 90 | 1.0 | — | 161 | 1.1 | (0.8, 1.5) | 29 | 1.0 | — | 76 | 1.6 | (1.03, 2.6) | ||
| Middle | 200 | 460 | 73 | 1.0 | (0.7, 1.4) | 152 | 0.9 | (0.7, 1.3) | 24 | 1.0 | (0.6, 1.6) | 54 | 1.0 | (0.6, 1.6) | |||
| High | 263 | 401 | 71 | 0.7 | (0.5, 1.01) | 107 | 0.7 | (0.5, 1.00) | ns | 39 | 1.1 | (0.7, 1.9) | 37 | 0.7 | (0.4, 1.2) | 0.02 | |
| Alcoholf (long term) | None | 276 | 476 | 87 | 1.0 | — | 153 | 1.1 | (0.8, 1.4) | 42 | 1.0 | — | 64 | 0.9 | (0.6, 1.3) | ||
| Moderate | 288 | 502 | 95 | 1.0 | (0.7, 1.4) | 160 | 1.0 | (0.7, 1.4) | 29 | 0.7 | (0.4, 1.1) | 61 | 0.8 | (0.5, 1.3) | |||
| High | 141 | 280 | 52 | 1.0 | (0.7, 1.5) | 107 | 1.0 | (0.7, 1.5) | ns | 21 | 0.9 | (0.5, 1.5) | 42 | 0.9 | (0.5, 1.5) | ns | |
ORs and 95% CIs adjusted for age, sex, race, center, smoking amount and other MTHFR polymorphism where appropriate.
Number of subjects varies slightly from Table I due to excluding observations with one or more missing values for adjustment variables.
Genotypes are homozygous for the common allele (wt), heterozygous (Het) and homozygous for the minor allele (Var); Het and Var genotypes are combined.
Cutpoints for middle and high based on controls, nutrient density/1000/kcal/day of folate (µg): 135/180 men and 152/201 women.
P-value for multiplicative interaction term; values >.0.05 not shown (ns).
High consumption of long-term alcohol (average of 10 and 20 years ago), g/day: ≥ 20 men, ≥ 10 women.