Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selected genetic polymorphisms involved in one-carbon metabolism and overall and subtype non-Hodgkin lymphoma (NHL) among participants with diet information, the NCI-SEER Case-Control Study, 1998-2000
| Gene, nucleotide change . | No. of controls*; n = 319 . | NHL cases . | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Overall . | Diffuse large B-cell lymphoma . | Follicular lymphoma . | Small lymphocytic lymphoma . | ||||||
| No. of cases*; n = 386 . | OR (95% CI) . | No. of cases*; n = 142 . | OR (95% CI) . | No. of cases*; n = 98 . | OR (95% CI) . | No. of cases*; n = 48 . | OR (95% CI) . | ||
| BHMT Ex8+453A>T | |||||||||
| AA | 122 | 160 | 1.0 (reference) | 46 | 1.0 (reference) | 46 | 1.0 (reference) | 23 | 1.0 (reference) |
| AT | 99 | 98 | 0.76 (0.53-1.10) | 30 | 0.83 (0.49-1.43) | 28 | 0.76 (0.44-1.33) | 13 | 0.65 (0.31-1.35) |
| TT | 19 | 13 | 0.54 (0.25-1.14) | 5 | 0.74 (0.26-2.13) | 2 | — | 3 | — |
| AT/TT | 118 | 111 | 0.73 (0.51-1.04) | 35 | 0.82 (0.49-1.37) | 30 | 0.68 (0.40-1.17) | 16 | 0.67 (0.34-1.33) |
| P trend | .05 | .43 | .08 | .34 | |||||
| CBS Ex13+41C>T | |||||||||
| CC | 142 | 149 | 1.0 (reference) | 56 | 1.0 (reference) | 36 | 1.0 (reference) | 16 | 1.0 (reference) |
| CT | 136 | 165 | 1.15 (0.83-1.59) | 58 | 1.08 (0.70-1.68) | 51 | 1.57 (0.96-2.58) | 17 | 1.14 (0.55-2.35) |
| TT | 33 | 59 | 1.68 (1.03-2.73) | 22 | 1.59 (0.85-2.98) | 8 | 1.01 (0.42-2.40) | 12 | 3.32 (1.43-7.71) |
| CT/TT | 169 | 224 | 1.25 (0.92-1.70) | 80 | 1.18 (0.78-1.79) | 59 | 1.46 (0.91-2.36) | 29 | 1.56 (0.81-3.01) |
| P trend | .05 | .21 | .35 | .02 | |||||
| FPGS Ex15-263T>C | |||||||||
| TT | 108 | 126 | 1.0 (reference) | 47 | 1.0 (reference) | 30 | 1.0 (reference) | 12 | 1.0 (reference) |
| CT | 160 | 171 | 0.91 (0.65-1.28) | 57 | 0.81 (0.51-1.28) | 45 | 1.04 (0.61-1.77) | 24 | 1.35 (0.65-2.83) |
| CC | 44 | 79 | 1.58 (1.00-2.49) | 31 | 1.64 (0.91-2.94) | 21 | 1.93 (0.98-3.80) | 11 | 2.47 (1.00-6.15) |
| CT/CC | 204 | 250 | 1.06 (0.77-1.45) | 88 | 0.98 (0.64-1.50) | 66 | 1.22 (0.74-2.01) | 35 | 1.57 (0.78-3.16) |
| P trend | .12 | .23 | .10 | .06 | |||||
| FTHFD Ex10-40T>G | |||||||||
| GG | 224 | 284 | 1.0 (reference) | 101 | 1.0 (reference) | 72 | 1.0 (reference) | 34 | 1.0 (reference) |
| GT | 76 | 85 | 0.90 (0.63-1.29) | 31 | 0.92 (0.57-1.50) | 23 | 0.93 (0.54-1.60) | 11 | 0.95 (0.46-1.97) |
| TT | 10 | 9 | 0.67 (0.26-1.68) | 5 | 1.08 (0.36-3.26) | 2 | — | 2 | — |
| GT/TT | 86 | 94 | 0.87 (0.62-1.23) | 36 | 0.94 (0.59-1.49) | 25 | 0.90 (0.53-1.52) | 13 | 1.00 (0.50-1.99) |
| P trend | .35 | .87 | .60 | .88 | |||||
| MTHFR Ex8-62A>C (1298A>C) | |||||||||
| AA | 135 | 183 | 1.0 (reference) | 66 | 1.0 (reference) | 48 | 1.0 (reference) | 24 | 1.0 (reference) |
| AC | 141 | 165 | 0.86 (0.63-1.19) | 61 | 0.90 (0.59-1.39) | 40 | 0.79 (0.48-1.29) | 20 | 0.79 (0.42-1.51) |
| CC | 38 | 35 | 0.67 (0.40-1.13) | 12 | 0.63 (0.31-1.30) | 10 | 0.72 (0.33-1.58) | 4 | — |
| AC/CC | 179 | 200 | 0.82 (0.61-1.11) | 73 | 0.85 (0.56-1.27) | 50 | 0.78 (0.49-1.23) | 24 | 0.75 (0.41-1.39) |
| P trend | .12 | .25 | .29 | .31 | |||||
| MTHFS IVS2-1411T>G | |||||||||
| TT | 80 | 99 | 1.0 (reference) | 35 | 1.0 (reference) | 21 | 1.0 (reference) | 16 | 1.0 (reference) |
| GT | 108 | 135 | 0.99 (0.67-1.46) | 37 | 0.80 (0.46-1.40) | 43 | 1.55 (0.84-2.85) | 17 | 0.79 (0.37-1.66) |
| GG | 42 | 32 | 0.58 (0.34-1.02) | 11 | 0.57 (0.26-1.24) | 9 | 0.78 (0.33-1.88) | 5 | 0.58 (0.20-1.71) |
| GT/GG | 150 | 167 | 0.87 (0.60-1.27) | 48 | 0.73 (0.44-1.24) | 52 | 1.33 (0.74-2.38) | 22 | 0.73 (0.36-1.47) |
| P trend | .11 | .15 | .95 | .30 | |||||
| MTR Ex26-20A>G | |||||||||
| AA | 169 | 186 | 1.0 (reference) | 58 | 1.0 (reference) | 53 | 1.0 (reference) | 26 | 1.0 (reference) |
| AG | 62 | 79 | 1.15 (0.77-1.71) | 23 | 1.09 (0.61-1.93) | 21 | 1.01 (0.56-1.84) | 12 | 1.18 (0.56-2.48) |
| GG | 10 | 7 | 0.65 (0.24-1.76) | 2 | — | 2 | — | 1 | — |
| AG/GG | 72 | 86 | 1.08 (0.74-1.58) | 25 | 1.02 (0.59-1.77) | 23 | 0.96 (0.54-1.71) | 13 | 1.10 (0.53-2.27) |
| P trend | .98 | .85 | .76 | .97 | |||||
| MTRR Ex5+136C>T | |||||||||
| TT | 230 | 278 | 1.0 (reference) | 101 | 1.0 (reference) | 69 | 1.0 (reference) | 36 | 1.0 (reference) |
| CT | 70 | 91 | 1.03 (0.72-1.48) | 35 | 1.05 (0.65-1.69) | 26 | 1.19 (0.69-2.03) | 10 | 0.90 (0.42-1.93) |
| CC | 8 | 11 | 1.19 (0.47-3.02) | 2 | — | 2 | — | 2 | — |
| CT/CC | 78 | 102 | 1.04 (0.74-1.48) | 37 | 0.99 (0.63-1.58) | 28 | 1.15 (0.69-1.94) | 12 | 0.99 (0.48-2.01) |
| P trend | .75 | .79 | .69 | .83 | |||||
| SHMT1 Ex12+138C>T | |||||||||
| CC | 127 | 125 | 1.0 (reference) | 37 | 1.0 (reference) | 30 | 1.0 (reference) | 21 | 1.0 (reference) |
| CT | 87 | 128 | 1.53 (1.05-2.22) | 40 | 1.59 (0.94-2.71) | 40 | 1.86 (1.07-3.24) | 16 | 1.11 (0.54-2.26) |
| TT | 26 | 17 | 0.66 (0.34-1.29) | 5 | 0.70 (0.25-1.96) | 3 | — | 3 | — |
| CT/TT | 113 | 145 | 1.33 (0.93-1.89) | 45 | 1.39 (0.83-2.32) | 43 | 1.54 (0.90-2.65) | 19 | 0.99 (0.51-1.95) |
| P trend | .68 | .65 | .66 | .71 | |||||
| SHMT1 Ex12+236C>T | |||||||||
| CC | 121 | 122 | 1.0 (reference) | 37 | 1.0 (reference) | 31 | 1.0 (reference) | 20 | 1.0 (reference) |
| CT | 93 | 134 | 1.46 (1.01-2.12) | 41 | 1.46 (0.86-2.47) | 42 | 1.68 (0.97-2.90) | 17 | 1.10 (0.54-2.25) |
| TT | 26 | 17 | 0.64 (0.33-1.25) | 5 | 0.66 (0.23-1.86) | 3 | — | 3 | — |
| CT/TT | 119 | 151 | 1.28 (0.90-1.82) | 46 | 1.28 (0.77-2.13) | 45 | 1.40 (0.82-2.39) | 20 | 0.99 (0.51-1.95) |
| P trend | .81 | .83 | .89 | .70 | |||||
| Gene, nucleotide change . | No. of controls*; n = 319 . | NHL cases . | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Overall . | Diffuse large B-cell lymphoma . | Follicular lymphoma . | Small lymphocytic lymphoma . | ||||||
| No. of cases*; n = 386 . | OR (95% CI) . | No. of cases*; n = 142 . | OR (95% CI) . | No. of cases*; n = 98 . | OR (95% CI) . | No. of cases*; n = 48 . | OR (95% CI) . | ||
| BHMT Ex8+453A>T | |||||||||
| AA | 122 | 160 | 1.0 (reference) | 46 | 1.0 (reference) | 46 | 1.0 (reference) | 23 | 1.0 (reference) |
| AT | 99 | 98 | 0.76 (0.53-1.10) | 30 | 0.83 (0.49-1.43) | 28 | 0.76 (0.44-1.33) | 13 | 0.65 (0.31-1.35) |
| TT | 19 | 13 | 0.54 (0.25-1.14) | 5 | 0.74 (0.26-2.13) | 2 | — | 3 | — |
| AT/TT | 118 | 111 | 0.73 (0.51-1.04) | 35 | 0.82 (0.49-1.37) | 30 | 0.68 (0.40-1.17) | 16 | 0.67 (0.34-1.33) |
| P trend | .05 | .43 | .08 | .34 | |||||
| CBS Ex13+41C>T | |||||||||
| CC | 142 | 149 | 1.0 (reference) | 56 | 1.0 (reference) | 36 | 1.0 (reference) | 16 | 1.0 (reference) |
| CT | 136 | 165 | 1.15 (0.83-1.59) | 58 | 1.08 (0.70-1.68) | 51 | 1.57 (0.96-2.58) | 17 | 1.14 (0.55-2.35) |
| TT | 33 | 59 | 1.68 (1.03-2.73) | 22 | 1.59 (0.85-2.98) | 8 | 1.01 (0.42-2.40) | 12 | 3.32 (1.43-7.71) |
| CT/TT | 169 | 224 | 1.25 (0.92-1.70) | 80 | 1.18 (0.78-1.79) | 59 | 1.46 (0.91-2.36) | 29 | 1.56 (0.81-3.01) |
| P trend | .05 | .21 | .35 | .02 | |||||
| FPGS Ex15-263T>C | |||||||||
| TT | 108 | 126 | 1.0 (reference) | 47 | 1.0 (reference) | 30 | 1.0 (reference) | 12 | 1.0 (reference) |
| CT | 160 | 171 | 0.91 (0.65-1.28) | 57 | 0.81 (0.51-1.28) | 45 | 1.04 (0.61-1.77) | 24 | 1.35 (0.65-2.83) |
| CC | 44 | 79 | 1.58 (1.00-2.49) | 31 | 1.64 (0.91-2.94) | 21 | 1.93 (0.98-3.80) | 11 | 2.47 (1.00-6.15) |
| CT/CC | 204 | 250 | 1.06 (0.77-1.45) | 88 | 0.98 (0.64-1.50) | 66 | 1.22 (0.74-2.01) | 35 | 1.57 (0.78-3.16) |
| P trend | .12 | .23 | .10 | .06 | |||||
| FTHFD Ex10-40T>G | |||||||||
| GG | 224 | 284 | 1.0 (reference) | 101 | 1.0 (reference) | 72 | 1.0 (reference) | 34 | 1.0 (reference) |
| GT | 76 | 85 | 0.90 (0.63-1.29) | 31 | 0.92 (0.57-1.50) | 23 | 0.93 (0.54-1.60) | 11 | 0.95 (0.46-1.97) |
| TT | 10 | 9 | 0.67 (0.26-1.68) | 5 | 1.08 (0.36-3.26) | 2 | — | 2 | — |
| GT/TT | 86 | 94 | 0.87 (0.62-1.23) | 36 | 0.94 (0.59-1.49) | 25 | 0.90 (0.53-1.52) | 13 | 1.00 (0.50-1.99) |
| P trend | .35 | .87 | .60 | .88 | |||||
| MTHFR Ex8-62A>C (1298A>C) | |||||||||
| AA | 135 | 183 | 1.0 (reference) | 66 | 1.0 (reference) | 48 | 1.0 (reference) | 24 | 1.0 (reference) |
| AC | 141 | 165 | 0.86 (0.63-1.19) | 61 | 0.90 (0.59-1.39) | 40 | 0.79 (0.48-1.29) | 20 | 0.79 (0.42-1.51) |
| CC | 38 | 35 | 0.67 (0.40-1.13) | 12 | 0.63 (0.31-1.30) | 10 | 0.72 (0.33-1.58) | 4 | — |
| AC/CC | 179 | 200 | 0.82 (0.61-1.11) | 73 | 0.85 (0.56-1.27) | 50 | 0.78 (0.49-1.23) | 24 | 0.75 (0.41-1.39) |
| P trend | .12 | .25 | .29 | .31 | |||||
| MTHFS IVS2-1411T>G | |||||||||
| TT | 80 | 99 | 1.0 (reference) | 35 | 1.0 (reference) | 21 | 1.0 (reference) | 16 | 1.0 (reference) |
| GT | 108 | 135 | 0.99 (0.67-1.46) | 37 | 0.80 (0.46-1.40) | 43 | 1.55 (0.84-2.85) | 17 | 0.79 (0.37-1.66) |
| GG | 42 | 32 | 0.58 (0.34-1.02) | 11 | 0.57 (0.26-1.24) | 9 | 0.78 (0.33-1.88) | 5 | 0.58 (0.20-1.71) |
| GT/GG | 150 | 167 | 0.87 (0.60-1.27) | 48 | 0.73 (0.44-1.24) | 52 | 1.33 (0.74-2.38) | 22 | 0.73 (0.36-1.47) |
| P trend | .11 | .15 | .95 | .30 | |||||
| MTR Ex26-20A>G | |||||||||
| AA | 169 | 186 | 1.0 (reference) | 58 | 1.0 (reference) | 53 | 1.0 (reference) | 26 | 1.0 (reference) |
| AG | 62 | 79 | 1.15 (0.77-1.71) | 23 | 1.09 (0.61-1.93) | 21 | 1.01 (0.56-1.84) | 12 | 1.18 (0.56-2.48) |
| GG | 10 | 7 | 0.65 (0.24-1.76) | 2 | — | 2 | — | 1 | — |
| AG/GG | 72 | 86 | 1.08 (0.74-1.58) | 25 | 1.02 (0.59-1.77) | 23 | 0.96 (0.54-1.71) | 13 | 1.10 (0.53-2.27) |
| P trend | .98 | .85 | .76 | .97 | |||||
| MTRR Ex5+136C>T | |||||||||
| TT | 230 | 278 | 1.0 (reference) | 101 | 1.0 (reference) | 69 | 1.0 (reference) | 36 | 1.0 (reference) |
| CT | 70 | 91 | 1.03 (0.72-1.48) | 35 | 1.05 (0.65-1.69) | 26 | 1.19 (0.69-2.03) | 10 | 0.90 (0.42-1.93) |
| CC | 8 | 11 | 1.19 (0.47-3.02) | 2 | — | 2 | — | 2 | — |
| CT/CC | 78 | 102 | 1.04 (0.74-1.48) | 37 | 0.99 (0.63-1.58) | 28 | 1.15 (0.69-1.94) | 12 | 0.99 (0.48-2.01) |
| P trend | .75 | .79 | .69 | .83 | |||||
| SHMT1 Ex12+138C>T | |||||||||
| CC | 127 | 125 | 1.0 (reference) | 37 | 1.0 (reference) | 30 | 1.0 (reference) | 21 | 1.0 (reference) |
| CT | 87 | 128 | 1.53 (1.05-2.22) | 40 | 1.59 (0.94-2.71) | 40 | 1.86 (1.07-3.24) | 16 | 1.11 (0.54-2.26) |
| TT | 26 | 17 | 0.66 (0.34-1.29) | 5 | 0.70 (0.25-1.96) | 3 | — | 3 | — |
| CT/TT | 113 | 145 | 1.33 (0.93-1.89) | 45 | 1.39 (0.83-2.32) | 43 | 1.54 (0.90-2.65) | 19 | 0.99 (0.51-1.95) |
| P trend | .68 | .65 | .66 | .71 | |||||
| SHMT1 Ex12+236C>T | |||||||||
| CC | 121 | 122 | 1.0 (reference) | 37 | 1.0 (reference) | 31 | 1.0 (reference) | 20 | 1.0 (reference) |
| CT | 93 | 134 | 1.46 (1.01-2.12) | 41 | 1.46 (0.86-2.47) | 42 | 1.68 (0.97-2.90) | 17 | 1.10 (0.54-2.25) |
| TT | 26 | 17 | 0.64 (0.33-1.25) | 5 | 0.66 (0.23-1.86) | 3 | — | 3 | — |
| CT/TT | 119 | 151 | 1.28 (0.90-1.82) | 46 | 1.28 (0.77-2.13) | 45 | 1.40 (0.82-2.39) | 20 | 0.99 (0.51-1.95) |
| P trend | .81 | .83 | .89 | .70 | |||||
We omitted estimates based on case counts less than 5 (indicated by —).
Unconditional logistic regression model adjusted for age at study entry (continuous), sex, and race (white, non–African American others).
Counts of controls and overall/subtype cases vary across polymorphisms due to (1) 2-step genotyping strategy (genotyping was not completed for certain polymorphisms [Table 1] in participants who provided only buccal cell samples [∼25%] if genotype information from blood-based DNA samples did not yield significant or suggestive associations with overall NHL) and (2) error in genotyping or insufficient DNA (2%-4% in general).