Background
Methods
Study participants
Diet assessment and baseline information collection
Genotyping
Statistical analysis
Results
Baseline characteristics of cases and controls
Characteristics | Cases | Controls | P-valuea |
---|---|---|---|
No.(%) | No.(%) | ||
Age (year)b | 63.1 ± 8.6 | 61.2 ± 9.0 | 0.001 |
BMI (kg/m2)b | 28.1 ± 5.0 | 27.3 ± 4.5 | 0.003 |
Sex | |||
Men | 399 (62.9) | 272 (58.5) | |
Women | 235 (37.1) | 193 (41.5) | 0.136 |
Race | |||
White | 615 (97.0) | 444 (95.5) | |
Other | 19 (3.0) | 21 (5.0) | 0.184 |
Family history of CRC | |||
Yes | 62 (9.8) | 35 (7.5) | |
No | 572 (90.2) | 430 (92.5) | 0.194 |
Level of education | |||
Lower than high school | 302 (47.8) | 140 (30.2) | |
High-school graduate | 100 (15.8) | 74 (16.0) | |
College | 177 (28.0) | 175 (37.7) | |
Bachelor or higher | 53 (8.4) | 75 (16.1) | < 0.001 |
Smoking history | |||
Current | 129 (20.3) | 58 (12.5) | |
Former | 325 (51.3) | 228 (49.4) | |
Never | 180 (28.4) | 176 (38.1) | < 0.001 |
Reported screening procedure | |||
Yes | 66 (10.4) | 107 (23.0) | |
No | 568 (89.6) | 358 (77.0) | < 0.001 |
Fruit intake (servings c/wk)b | 9.7 ± 8.3 | 10.9 ± 8.1 | 0.027 |
Total vitamin D intake (μg/d)b | 8.7 ± 6.4 | 10.2 ± 7.9 | 0.001 |
Total calcium intake (mg/d)b | 1019.8 ± 488.8 | 1097.1 ± 567.7 | 0.018 |
Milk (g/d)b | 287.1 ± 278.0 | 299.9 ± 295.5 | 0.465 |
Total dairy products (g/d)b | 364.5 ± 303.3 | 389.9 ± 340.0 | 0.200 |
Tumor location | |||
Colon | 417 (65.8) | – | – |
Rectum | 217 (34.2) | – | – |
Stage at diagnosis | |||
I/II | 288 (58.9) | – | – |
III/IV | 201 (41.1) | – | – |
Chemoradiotherapy | |||
Yes | 106 (19.9) | – | – |
No | 427 (80.1) | – | – |
MSI status | |||
MSS/MSI-L | 446 (88.0) | – | – |
MSI-H | 61 (12.0) | – | – |
BRAF mutation status | |||
Wild type | 445 (89.2) | – | – |
BRAF mutant | 54 (10.8) | – | – |
Association of rs2282679 genotype with CRC risk
rs2282679 Genotype/Allele | Cases N(%) | Controls N(%) | OR (95% CI)a | OR (95% CI)b |
---|---|---|---|---|
All cases vs. controls | ||||
AA | 309 (48.5) | 245 (50.1) | 1.00 | 1.00 |
AC | 282 (44.3) | 208 (42.5) | 1.08 (0.82–1.41) | 1.10 (0.83–1.47) |
CC | 46 (7.2) | 36 (7.4) | 1.06 (0.63–1.77) | 1.21 (0.70–2.09) |
P trendc | 0.647 | 0.403 | ||
CC + AC (vs. AA) | 328 (51.5) | 244 (49.9) | 1.07 (0.83–1.39) | 1.12 (0.85–1.47) |
CC (vs. AC + AA) | 46 (7.2) | 36 (7.4) | 1.02 (0.62–1.68) | 1.15 (0.68–1.97) |
Per C allele | 1.05 (0.85–1.29) | 1.10 (0.88–1.37) | ||
BRAF V600E mutant cases vs. controls | ||||
AA | 25 (46.3) | 245 (50.1) | 1.00 | 1.00 |
CC + ACd | 29 (53.7) | 244 (49.9) | 1.03 (0.54–1.96) | 1.10 (0.56–2.16) |
BRAF wild-type cases vs. controls | ||||
AA | 223 (50.1) | 245 (50.1) | 1.00 | 1.00 |
CC + ACd | 222 (49.9) | 244 (49.9) | 1.08 (0.82–1.42) | 1.10 (0.82–1.47) |
MSI-H cases vs. controls | ||||
AA | 31 (50.8) | 245 (50.1) | 1.00 | 1.00 |
CC + ACd | 30 (49.2) | 244 (49.9) | 0.99 (0.56–1.80) | 1.03 (0.56–1.90) |
MSS/MSI-Low cases vs. controls | ||||
AA | 223 (50.0) | 245 (50.1) | 1.00 | 1.00 |
CC + ACd | 223 (50.0) | 244 (49.9) | 1.09 (0.83–1.44) | 1.15 (0.86–1.53) |
Interactions of rs2282679 genotype with dietary characteristics in relation to CRC risk
GC rs2282679 genotype |
P
interaction
b
| ||
---|---|---|---|
AA OR (95% CI)a | AC + CC OR (95% CI)a | ||
Total vitamin D intake (μg/d) | |||
Highest tertile (≥10.1) | 1.00 |
1.65 (1.01–2.71)
| |
Lowest tertile (< 5.0) |
2.50 (1.52–4.09)
|
1.72 (1.03–2.90)
| 0.019 |
Total calcium intake (mg/d) | |||
Highest tertile (≥1195.4) | 1.00 | 1.45 (0.89–2.36) | |
Lowest tertile (< 761.4) | 1.21 (0.73–2.00) | 1.63 (0.95–2.81) | 0.827 |
Milk (g/d) | |||
Highest tertile (≥321.3) | 1.00 | 1.61 (0.99–2.61) | |
Lowest tertile (< 146.5) | 1.46 (0.90–2.38) | 1.21 (0.72–2.04) | 0.056 |
Total dairy products (g/d) | |||
Highest tertile (≥432.0) | 1.00 | 1.61 (0.99–2.61) | |
Lowest tertile (< 210.6) | 1.44 (0.90–2.32) | 1.27 (0.75–2.14) | 0.079 |
Association of rs2282679 genotype and survival outcome
rs2282679 Genotype/Allele | Disease-Free Survival |
P
interaction
c
| Overall Survival |
P
interaction
c
| ||
---|---|---|---|---|---|---|
No. of Eventsa /At Risk | HR (95% CI)b | No. of Eventsa /At Risk | HR (95% CI)b | |||
Total colorectal cancer | ||||||
AA | 83/245 | 1.00 | 69/245 | 1.00 | ||
AC | 80/207 | 1.33 (0.94–1.88) | 68/208 | 1.24 (0.85–1.81) | ||
CC | 16/36 |
1.93 (1.06–3.52)
| 13/36 | 1.60 (0.85–3.02) | ||
P trendd | 0.020 | 0.107 | ||||
CC + AC (vs. AA) | 96/243 |
1.40 (1.00–1.95)
| 81/244 | 1.29 (0.90–1.85) | ||
CC (vs. AC + AA) | 16/36 | 1.69 (0.95–2.99) | 13/36 | 1.44 (0.79–2.65) | ||
Per C allele |
1.36 (1.05–1.77)
| 1.26 (0.95–1.66) | ||||
BRAF Val600Glu mutant | ||||||
AA | 8/20 | 1.00 | 5/20 | 1.00 | ||
CC + ACe | 8/26 | 0.95 (0.25–3.62) | 7/26 | 1.53 (0.47–4.95) | ||
BRAF wild-type | ||||||
AA | 65/200 | 1.00 | 55/200 | 1.00 | ||
CC + AC e | 83/195 |
1.58 (1.12–2.23)
| 0.043 | 70/196 | 1.33 (0.93–1.91) | 0.892 |
MSI-H | ||||||
AA | 3/25 | 1.00 | 0/26 | 1.00 | ||
CC + ACe | 5/28 | 1.26 (0.18–8.96) | 3/28 | NCf | ||
MSS/MSI-L | ||||||
AA | 76/204 | 1.00 | 65/204 | 1.00 | ||
CC + ACe | 87/203 | 1.34 (0.97–1.87) | 0.702 | 74/204 | 1.26 (0.89–1.77) | 0.210 |
Interactions of rs2282679 genotype with dietary characteristics in relation to CRC survival
GC rs2282679 genotype |
P
interaction
b
| ||
---|---|---|---|
AA HR (95% CI)a | AC + CC HR (95% CI)a | ||
Disease-Free Survival | |||
Dietary vitamin D (μg/d) | |||
Highest tertile (≥7.1) | 1.00 | 1.65 (0.97–2.82) | |
Lowest tertile (< 4.6) | 1.03 (0.58–1.83) | 1.08 (0.56–2.08) | 0.191 |
Dietary calcium (mg/d) | |||
Highest tertile (≥1120.2) | 1.00 | 1.58 (0.92–2.71) | |
Lowest tertile (< 702.1) | 1.06 (0.59–1.91) | 1.14 (0.62–2.11) | 0.355 |
Milk (g/d) | |||
Highest tertile (≥274.6) | 1.00 | 1.63 (0.92–1.84) | |
Lowest tertile (< 128.1) | 1.21 (0.68–2.16) | 0.97 (0.51–1.84) | 0.083 |
Total dairy products (g/d) | |||
Highest tertile (≥411.8) | 1.00 | 1.51 (0.87–2.60) | |
Lowest tertile (< 199.2) | 1.00 (0.57–1.77) | 0.99 (0.53–1.83) | 0.289 |
Overall Survival | |||
Dietary vitamin D (μg/d) | |||
Highest tertile (≥7.1) | 1.00 |
2.11 (1.29–3.74)
| |
Lowest tertile (< 4.6) | 1.28 (0.68–2.42) | 1.11 (0.54–2.27) | 0.040 |
Dietary calcium (mg/d) | |||
Highest tertile (≥1120.2) | 1.00 |
1.93 (1.08–3.46)
| |
Lowest tertile (< 702.1) | 1.55 (0.82–2.91) | 1.18 (0.59–2.35) | 0.043 |
Milk (g/d) | |||
Highest tertile (≥274.6) | 1.00 |
2.36 (1.26–4.44)
| |
Lowest tertile (< 128.1) |
2.09 (1.09–4.02)
| 1.26 (0.61–2.62) | 0.004 |
Total dairy products (g/d) | |||
Highest tertile (≥411.8) | 1.00 |
2.03 (1.11–3.72)
| |
Lowest tertile (< 199.2) | 1.77 (0.94–3.33) | 1.27 (0.63–2.58) | 0.024 |