Supplementary information

Online resource 1. The genotype and allele frequency of the six SNPs examined in 1257 control subjects

Online resource 2. Linkage disequilibrium among controls (D´)

Online resource 3: Descriptive characteristics of fruit, vegetable and total vitamin C intake among controls.

Online resource 34. Association between CLL and the three continuous variables of diet (100g/day increase of fruit intake, 100g/day increase of vegetable intake, 100mg/day increase of total vitamin C intake) stratified by disease stages, time from diagnosis to recruitment and CLL treatment.

Online resource 45. Analyses of CLL and polymorphisms using log-additive models stratified by time from diagnosis to recruitment, by Rai stages and by treatment for CLL

Online resource 56. Substantial changes in diet in the last 5 years in cases and controls

Online resource 67. Association between total carbohydrate, sugar, complex carbohydrate and fibre intake in relation to CLL

Online resource 1. The genotype and allele frequency of the six examined SNP in 1257 control subjects

SNP / HWE p-values / Allele (1/2) / Genotype counts (frequency) / Allele counts (frequency)
1 / 2 / 1/1 / 1/2 / 2/2 / 1 / 2
rs1715364 / 0.69 / A / G / 381 (30%) / 627 (50%) / 249 (20%) / 1389 (55%) / 1125 (45%)
rs6133175 / 0.93 / A / G / 581 (46%) / 542 (43%) / 134 (11%) / 1704 (68%) / 810 (32%)
rs1776948 / 0.30 / G / A / 379 (30%) / 632 (50%) / 246 (20%) / 1390 (55%) / 1124 (45%)
rs6139587 / 0.33 / A / T / 427 (34%) / 630 (50%) / 200 (16%) / 1484 (59%) / 1030 (41%)
rs369270 / 0.61 / A / G / 464 (37%) / 600 (48%) / 193 (15%) / 1528 (61%) / 986 (39%)
rs6052937 / 0.52 / C / A / 839 (67%) / 384 (31%) / 34 (3%) / 2062 (82%) / 452 (18%)

Online resource 2. Linkage disequilibrium among controls (D´)

Online resource 3: Descriptive characteristics of fruit, vegetable and total vitamin C intake among controls (N= 1602).

factors / Fruit intake
mean (SD), g/day / Vegetable intake
mean (SD), g/day / Vitamin C intake
mean (SD), mg/day
Region
Barcelona / 324.5 (207) / 196.1 (147.3) / 159.4 (100.7)
Asturias / 323 (282.6) / 160.3 (102.6) / 157.1 (112.1)
Girona / 318.7 (198.5) / 166.4 (67.9) / 150.7 (77.6)
Cantabria / 309 (221.9) / 135.4 (95.4) / 146.1 (94.8)
Granada / 365.9 (217.6) / 185.5 (116.7) / 168.2 (96.7)
Prob > F / 0.23 / < 0.001 / 0.257
Age group
≤60 / 301.6 (229.6) / 173.2 (136.4) / 158.1 (105.4)
61-70 / 326.2 (200.2) / 174.9 (130.6) / 155 (96.9)
≥71 / 350.4 (244.2) / 170.8 (109.6) / 156 (97.7)
Prob > F / 0.02 / 0.916 / 0.913
Sex
Male / 310.3 (223.4) / 163.2 (125.6) / 144.8 (96.6)
Female / 345.3 (224.1) / 187.5 (127.5) / 173 (102.6)
Prob > F / 0.01 / 0.002 / < 0.001
Education
Lower / 340.3 (219.7) / 174.2 (126.4) / 159 (100.8)
Higher / 306 (228.3) / 172 (127.6) / 153.2 (99.2)
Prob > F / 0.01 / 0.774 / 0.342
Smoking
Never / 361.7 (200.7) / 186.3 (128.4) / 170.6 (94.7)
Former / 321.1 (239.4) / 175.3 (133.9) / 151.4 (100.8)
Current / 247.9 (224.9) / 138.3 (100.6) / 133.5 (105.7)
Prob > F / < 0.001 / < 0.001 / < 0.001
Family history of haematologic cancer
No / 324.4 (226.4) / 174 (128.9) / 157 (100.9)
Yes / 320.5 (181.8) / 177.2 (118.4) / 145.3 (81.5)
Prob > F / 0.91 / 0.864 / 0.423
Body mass index
<25 / 309.6 (216.1) / 164.7 (107.4) / 156.2 (94.5)
25-29 / 331.6 (229.2) / 168 (124.1) / 152 (99)
≥30 / 334.7 (226.7) / 195.2 (153.9) / 164.5 (109.3)
Prob > F / 0.26 / 0.006 / 0.281
Diabetes
No / 326.9 (232.6) / 172.3 (130.7) / 158 (103.4)
Yes / 313.8 (174.6) / 178.5 (105) / 148.2 (79.9)
Prob > F / 0.48 / 0.553 / 0.234
Alcolhol consumption
Tertile 1 / 360.9 (212.3) / 188 (156.6) / 167 (102.8)
Tertile 2 / 324.5 (196.2) / 181 (129.9) / 162.9 (94.5)
Tertile 3 / 308.5 (253) / 158.4 (105.8) / 144.9 (103.4)
Prob > F / 0.02 / 0.005 / 0.007
Total energy intake
Quartile 1 / 259.3 (173.3) / 135.5 (92.3) / 121.9 (73.8)
Quartile 2 / 296.4 (176.4) / 163.1 (101.3) / 142 (76.2)
Quartile 3 / 352 (248.4) / 181.4 (109) / 167.7 (105.1)
Quartile 4 / 389.8 (260.9) / 212.4 (177.4) / 193.4 (122.3)
Prob > F / < 0.001 / < 0.001 / < 0.001

SD: standard deviation, Prob: probability

Online resource 3 4. Odds ratios for chronic lymphocytic leukemia by genetic variants, stratifying cases by Rai stages, by time from diagnosis to recruitment (TDR) and treatment for CLL

Online resource 5 4 Association between CLL and the three continuous variables of diet (100g/day increase of fruit intake, 100g/day increase of vegetable intake, 100mg/day increase of total vitamin C intake) stratified by disease stages, prevalence time and CLL treatment).

Fruit / Fruit / total vitamin C
Case
number / 1 unit/day increase / 100g/day increase / 100mg/day increase
OR* (95% CI) / P-int / OR* (95% CI) / P-int / OR* (95% CI) / P-int
Overall / 345 / 1.06 (0.98 to 1.14) / 1.04 (0.98 to 1.10) / 1.02 (0.90 to 1.17)
p-value / 0.15 / 0.23 / 0.72
Time from diagnosis to interview
TDR≤ 6 mths / 65 / 1.11 (0.97 to 1.28) / 1.08 (0.97 to 1.19) / 1.19 (0.94 to 1.49)
TDR> 6 mths / 280 / 1.05 (0.96 to 1.14) / 0.54 / 1.03 (0.96 to 1.09) / 0.52 / 0.98 (0.84 to 1.14) / 0.27
TDR – 6 mths to 4.9yrs / 197 / 1.03 (0.93 to 1.14) / 1.01 (0.93 to 1.09) / 0.95 (0.80 to 1.14)
TDR – 5yrs or more / 83 / 1.08 (0.94 to 1.24) / 1.06 (0.97 to 1.17) / 1.04 (0.81 to 1.34)
Rai stages
Rai 0 / 192 / 1.08( 0.99 to 1.19) / 1.05(0.98 to 1.13) / 1.02 (0.86 to 1.21)
Rai I-IV / 146 / 1.01 (0.90 to 1.13) / 0.40 / 1.00 (0.92 to 1.09) / 0.37 / 1.02 (0.84 to 1.24) / 0.90
Treated for CLL
never treated / 267 / 1.07 (0.98 to 1.16) / 1.04 (0.98 to 1.11) / 1.01 (0.87 to 1.17)
ever treated / 78 / 1.02 (0.88 to 1.19) / 0.54 / 1.01 (0.90 to 1.13) / 0.48 / 1.08 (0.85 to 1.38) / 0.54
Case
number / Vegetables / Vegetables
1 unit/day increase / 100g/day increase
OR* (95% CI) / P-int / OR* (95% CI) / P-int
Overall / 345 / 0.95 (0.88 to 1.02) / 0.90 (0.80 to 1.01)
p-value / 0.13 / 0.06
Time from diagnosis to interview
TDR≤ 6 mths / 65 / 0.97 (0.84 to 1.12) / 0.93 (0.74 to 1.17)
TDR>6 mths / 280 / 0.94 (0.87 to 1.02) / 0.72 / 0.89 (0.79 to 1.01) / 0.82
TDR – 6 mths to 4.9yrs / 197 / 0.94 (0.86 to 1.03) / 0.89 (0.77 to 1.02)
TDR – 5yrs or more / 83 / 0.95 (0.83 to 1.09) / 0.91 (0.74 to 1.13)
Rai stages
Rai 0 / 192 / 0.94 (0.85 to 1.03) / 0.86 (0.74 to 0.99)
Rai I-IV / 146 / 0.96 (0.86 to 1.06) / 0.43 / 0.95 (0.82 to 1.12) / 0.10
Treated for CLL
never treated / 267 / 0.94 (0.87 to 1.02) / 0.88 (0.77 to 1.00)
ever treated / 78 / 0.97 (0.85 to 1.11) / 0.41 / 0.98 (0.80 to 1.20) / 0.13

*Adjusted for age, sex, region, education, smoking, diabetes, alcohol, total energy intake, body mass index and family history of haematological cancer

TDR: time from diagnosis to recruitment; mths: months; yrs: years

Online resource 56 Substantial changes in diet in the last 5 years in cases and controls

CONTROLS / CASES / CASES stratified by time from diagnosis to recruitment
N (%) / N (%) / P-het / < 6mths / 6 mths–4.9yrs / 5yrs or more / P-het
Have you changed substantially your diet in the last 5 years? / N= 1602 / N= 345 / N= 65 / N= 197 / N= 83
YES / 575 (36%) / 129 (37%) / 20 (31%) / 73 (37%) / 36 (43%)
NO / 835 (52%) / 197 (57%) / 0.69 / 40 (62%) / 110 (55%) / 47 (57%) / 0.65
Missing / 192 (12%) / 19 (6%) / 5 (8%) / 14 (7%) / 0 (0%)
Changes in: / N= 575 / N= 129 / N= 30 / N= 73 / N= 36
Fruit consumption
Higher / 239 (42%) / 45 (35%) / 10 (50%) / 21 (29%) / 14 (38%)
No change / 262 (46%) / 65 (50%) / 9 (45%) / 38 (52%) / 18 (50%)
Lower / 42 (7%) / 12 (9%) / 0 (0%) / 9 (12%) / 3 (8%)
Do not consume / 5 (<1%) / 1 (<1%) / 0.52 / 0 (0%) / 0 (0%) / 1 (3%) / 0.36
Missing / 27 (5%) / 6 (5%) / 1 (5%) / 5 (7%) / 0 (0%)
Vegetable consumption
Higher / 275 (48%) / 53 (41%) / 10 (50%) / 30 (41%) / 13 (36%)
No change / 239 (42%) / 62 (48%) / 9 (45%) / 34 (47%) / 19 (53%)
Lower / 31 (5%) / 6 (5%) / 0 (0%) / 2 (3%) / 4 (11%)
Do not consume / 5 (<1%) / 0 (0%) / 0.35 / 0 (0%) / 0 (0%) / 0 (0%) / 0.31
Missing / 25(4%) / 8 (6%) / 1 (5%) / 7 (10%) / 0 (0%)

N: number mth: months; yr: years

Online resource 6 7 Association between total carbohydrate, sugar, complex carbohydrate and fibre intake in relation to CLL

CONTROLS / CASES
N (%) / N (%) / Basic adjustment a
OR & 95% CI / Full adjustment b
OR & 95% CI
1602 / 345
TOTAL CARBOHYDRATES INTAKE (g/day)
<143.2 / 382 (24%) / 75 (22%) / 1.13 (0.80 to 1.60) / REF
143.2 - 180.6 / 389 (24%) / 85 (25%) / 0.98 (0.69 to 1.40) / 1.15 (0.80 to 1.67)
180.6 - 223.6 / 403 (25%) / 76 (22%) / 1.38 (0.99 to 1.94) / 0.98 (0.65 to 1.49)
>223.6 / 428 (27%) / 109 (32%) / 1.13 (0.80 to 1.60) / 1.43 (0.86 to 2.39)
P-trend / 0.11 / 0.35
TOTAL SUGAR INTAKE (g/day)
<74.1 / 372 (23%) / 69 (20%) / REF / REF
74.1 - 95.7 / 398 (25%) / 83 (24%) / 1.13 (0.79 to 1.61) / 1.15 (0.79 to 1.66)
95.7 - 122.7 / 429 (27%) / 86 (25%) / 1.10 (0.78 to 1.56) / 1.12 (0.76 to 1.65)
>122.7 / 403 (25%) / 107 (31%) / 1.50 (1.07 to 2.11) / 1.56 (1.00 to 2.43)
P-trend / 0.02 / 0.08
TOTAL COMPLEX CARBOHYDRATE INTAKE (g/day)
<64.1 / 406 (25%) / 79 (23%) / REF / REF
64.1 - 86.4 / 382 (24%) / 78 (23%) / 1.04 (0.73 to 1.47) / 0.98 (0.68 to 1.41)
86.4 - 112.4 / 399 (25%) / 97 (28%) / 1.27 (0.91 to 1.79) / 1.19 (0.81 to 1.73)
>112.4 / 415 (26%) / 91 (26%) / 1.16 (0.81 to 1.65) / 0.98 (0.61 to 1.56)
P-trend / 0.27 / 0.79
TOTAL FIBRE INTAKE (g/day)
<15.5 / 357 (22%) / 68 (20%) / REF / REF
15.5 - 20.3 / 389 (24%) / 93 (27%) / 1.16 (0.81 to 1.64) / 1.05 (0.73 to 1.51)
20.3 - 25.6 / 406 (25%) / 77 (22%) / 0.93 (0.65 to 1.33) / 0.81 (0.55 to 1.20)
>25.6 / 450 (28%) / 107 (31%) / 1.13 (0.81 to 1.60) / 0.90 (0.59 to 1.37)
P-trend / 0.76 / 0.38

a: Age, sex, region and education

b: Age, sex, region, education, smoking, diabetes, current alcohol intake, total energy intake, body mass index and family history of haematological cancer