Background
Methods
Subjects
Determination of the 8q24 loci genotype
Exposure data
Statistical analysis
Results
Variables | Cases | Controls | p-values | ||
---|---|---|---|---|---|
Total
| 481 | 962 | |||
Sex
| 1.00 | ||||
Male | 300 | 62.4% | 600 | 62.4% | |
Female | 181 | 37.6% | 362 | 37.6% | |
Age (years) | 0.803 | ||||
< 40 | 20 | 4.2% | 39 | 4.1% | |
40-49 | 50 | 10.4% | 105 | 10.9% | |
50-59 | 169 | 35.1% | 328 | 34.1% | |
60-69 | 164 | 34.1% | 353 | 36.7% | |
70- | 78 | 16.2% | 137 | 14.2% | |
Mean age (SD) | 60 (10.2) | 60 (9.86) | |||
Site of Cancer | |||||
Colon | 245 | 50.9% | |||
Rectum | 236 | 49.1% | |||
Smoking | 0.102 | ||||
None | 215 | 44.7% | 493 | 51.3% | |
Low-moderate (< 20 pack-years) | 59 | 12.3% | 116 | 12.1% | |
Heavy (≥ 20 pack-years) | 203 | 42.2% | 345 | 35.9% | |
Unknown | 4 | 0.8% | 8 | 0.8% | |
Drinking | 0.695 | ||||
None | 190 | 39.5% | 383 | 39.8% | |
Low (< 5 g ethanl/day) | 64 | 13.3% | 125 | 13.0% | |
Moderate (5≤ and < 23 g ethanol/day) | 85 | 17.7% | 196 | 20.4% | |
High (≥ 23 g ethanol/day) | 135 | 28.1% | 243 | 25.3% | |
Unknown | 7 | 1.5% | 15 | 1.6% | |
Daily folate consumption | 0.857 | ||||
T1 (≤ 262.0 μg/day) | 153 | 31.8% | 286 | 29.7% | |
T2 (≤ 346.6 μg/day) | 158 | 32.9% | 318 | 33.1% | |
T3 (> 346.6 μg/day) | 162 | 33.7% | 341 | 35.5% | |
Unknown | 8 | 1.7% | 17 | 1.8% | |
Body-Mass Index (BMI) kg/m2
| 0.923 | ||||
< 22.5 | 206 | 42.8% | 397 | 41.3% | |
22.5 ≤ and < 25 | 157 | 32.6% | 314 | 32.6% | |
25 ≤ and < 27.5 | 73 | 15.2% | 162 | 16.8% | |
≥ 27.5 | 41 | 8.5% | 79 | 8.2% | |
Unknown | 4 | 0.8% | 10 | 1.0% | |
Family history of colorectal cancer in the first degree relatives | 0.014 | ||||
No | 453 | 94.2% | 932 | 96.9% | |
Yes | 28 | 5.8% | 30 | 3.1% | |
Average recreational exercise | 0.329 | ||||
None | 192 | 39.9% | 349 | 36.3% | |
< 0.5 hour/day | 194 | 40.3% | 398 | 41.4% | |
0.5 ≤ hour/day | 95 | 19.8% | 215 | 22.4% |
Allelic model | Genotype model | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Model 1 *1 | Model 2 *2 | Heterozygote | Minor homozygote | |||||||||||||
8q24 locus | Genotype | OR | 95% CI | p-value | ORa
| 95% CI | p-value | ORa
| 95% CI | p-value | ORa
| 95% CI | p-value | |||
rs6983267 (Minor allele: G, MAF*1 in controls = 0.338)
| ||||||||||||||||
TT | TG | GG | UK*4 | |||||||||||||
case/control | 181/418 | 222/436 | 73/107 | 3/1 | 1.22 | 1.04-1.44 | 0.0144 | 1.25 | 1.06-1.48 | 0.0071 | 1.19 | 0.93-1.52 | 0.1665 | 1.64 | 1.15-2.35 | 0.0063 |
rs10090154 (Minor allele: T, MAF in controls = 0.153)
| ||||||||||||||||
CC | CT | TT | UK | |||||||||||||
case/control | 355/689 | 112/247 | 11/23 | 3/3 | 0.90 | 0.72-1.12 | 0.3443 | 0.87 | 0.69-1.09 | 0.2140 | 0.83 | 0.63-1.08 | 0.1690 | 0.90 | 0.43-1.89 | 0.7854 |
rs6983267 allelic model | |||||||||
---|---|---|---|---|---|---|---|---|---|
Model 1*1
|
Model*2
| ||||||||
Exposure | Number of controls with each genotype (TT/TG/GG) | Number of cases with each genotype (TT/TG/GG) | OR*1 | 95% CI | p-value | OR | 95% CI | p-value | Interaction P |
Sex
| 0.181 | ||||||||
Male |
122/133/43
|
259/270/70
| 1.11 | 0.91-1.37 | 0.295 | 1.14 | 0.93-1.41 | 0.212 | |
Female |
61/89/30
|
159/166/37
| 1.44 | 1.10-1.88 | 0.007 | 1.34 | 1.01-1.78 | 0.040 | |
Smoking
| 0.401 | ||||||||
None |
73/106/35
|
206/232/55
| 1.34 | 1.05-1.70 | 0.018 | 1.29 | 1.01-1.65 | 0.042 | |
Low-moderate (< 20 pack-years) |
19/31/9
|
52/52/12
| 1.51 | 0.93-2.43 | 0.094 | 1.49 | 0.89-2.49 | 0.130 | |
Heavy (≥ 20 pack-years) |
88/84/29
|
158/147/39
| 1.11 | 0.86-1.43 | 0.423 | 1.12 | 0.86-1.44 | 0.407 | |
Drinking
| 0.437 | ||||||||
None |
69/92/30
|
166/179/38
| 1.36 | 1.04-1.76 | 0.023 | 1.35 | 1.03-1.77 | 0.028 | |
Low (< 5 g ethanl/day) |
23/29/12
|
51/58/16
| 1.25 | 0.81-1.93 | 0.308 | 1.44 | 0.91-2.28 | 0.124 | |
Moderate (5≤ and < 23 g ethanol/day) |
34/41/9
|
85/83/27
| 0.98 | 0.67-1.43 | 0.918 | 0.99 | 0.67-1.46 | 0.941 | |
High (≥ 23 g ethanol/day) |
55/59/19
|
112/108/23
| 1.22 | 0.89-1.67 | 0.217 | 1.22 | 0.88-1.69 | 0.231 | |
Daily folate consumption
| 0.694 | ||||||||
T1 (≤ 262.0 μg/day) |
54/73/25
|
112/137/37
| 1.14 | 0.85-1.53 | 0.375 | 1.22 | 0.90-1.66 | 0.197 | |
T2 (≤ 346.6 μg/day) |
59/75/22
|
104/141/36
| 1.21 | 0.91-1.61 | 0.191 | 1.25 | 0.93-1.67 | 0.141 | |
T3 (> 346.6 μg/day) |
66/72/24
|
157/152/32
| 1.24 | 0.94-1.64 | 0.135 | 1.30 | 0.97-1.73 | 0.080 | |
Body-Mass Index (BMI) kg/m
2
| 0.678 | ||||||||
< 22.5 |
73/100/32
|
177/176/44
| 1.34 | 1.05-1.72 | 0.020 | 1.43 | 1.10-1.85 | 0.007 | |
22.5 ≤ and < 25 |
69/69/19
|
128/148/37
| 0.93 | 0.70-1.25 | 0.663 | 0.93 | 0.69-1.25 | 0.637 | |
25 ≤ and < 27.5 |
23/34/16
|
74/69/19
| 1.58 | 1.06-2.36 | 0.024 | 1.67 | 1.09-2.55 | 0.018 | |
≥ 27.5 |
18/17/5
|
31/41/7
| 0.98 | 0.54-1.79 | 0.944 | 1.06 | 0.54-2.10 | 0.863 | |
Family history of colorectal cancer in the first degree relatives | 0.765 | ||||||||
No |
169/212/69
|
404/422/105
| 1.24 | 1.05-1.46 | 0.011 | 1.26 | 1.06-1.48 | 0.008 | |
Yes |
14/10/4
|
14/14/2
| 1.09 | 0.50-2.38 | 0.833 | 0.84 | 0.29-2.43 | 0.741 | |
Average recreational exercise | 0.109 | ||||||||
None |
77/90/24
|
161/140/48
| 1.10 | 0.85-1.42 | 0.462 | 1.13 | 0.87-1.47 | 0.356 | |
< 0.5 hour/day |
73/89/31
|
158/199/40
| 1.20 | 0.93-1.56 | 0.163 | 1.20 | 0.92-1.57 | 0.174 | |
0.5 ≤ hour/day |
33/43/18
|
99/97/19
| 1.59 | 1.11-2.28 | 0.012 | 1.70 | 1.15-2.50 | 0.008 |
Discussion
Author | Year | Case/Control | Country | Study subjects | Per allele OR (95%CI) | Adjustment |
---|---|---|---|---|---|---|
Haiman et al.
| 2007 |
1,807/5,511
|
USA
|
Pooled
|
1.25 (1.12-1.38)
| Sex |
217/1,049 | African American | 1.37 (0.98-1.91) | Sex | |||
381/1,197 | Japanese American | 1.13 (0.96-1.34) | Sex | |||
61/347 | Native Hawaiian | 1.59 (1.02-2.47) | Sex | |||
251/1,007 | Latinos | 1.26 (1.02-1.55) | Sex | |||
214/973 | European Americans | 1.28 (1.03-1.58) | Sex | |||
Tomlinson et al.
| 2007 |
7,954/6,206
|
UK
|
CRC pooled
|
1.21 (1.15-1.27)
| Crude |
620/960 | Panel A CRC White UK residents | 1.38 (1.19-1.59) | Crude | |||
4,361/3,752 | Panel B White UK residents | 1.19 (1.12-1.26) | Crude | |||
1,901/1,079 | Panel C | 1.21 (1.09-1.35) | Crude | |||
1,072/415 | Panel D European Ancestry | 1.13 (0.96-1.33) | Crude | |||
1,425/2,255
|
Adenoma pooled
|
1.22 (1.10-1.34)
| Crude | |||
407/1,027 | Panel A Adenoma White UK residents | 1.53 (1.29-1.81) | Crude | |||
607/765 | Panel E | 1.05 (0.90-1.23) | Crude | |||
411/463 | Panel F | 1.13 (0.93-1.37) | Crude | |||
Poynter et al.
| 2007 |
1,339/2,191
|
USA
|
Population -- based
| 1.11 (0.96-1.29) | Age and sex |
Tuupanen et al.
| 2008 | 996/1,012 |
Finland
|
Population-based
| 1.22 (1.08-1.38) | Crude |
Berndt et al.
| 2008 |
3,134/4,454
|
USA
|
Colorectal neoplasms pooled
|
1.16 (1.07-1.25)
| Age, sex, and study |
547/1,656 | PLCO | 1.17 (1.01-1.35) | Age and sex | |||
1,174/1,293 | PLCO adenoma | 1.24 (1.11-1.39) | Age and sex | |||
364/363 | PLCO II | 0.93 (0.75-1.16) | Age and sex | |||
544/542 | NHS | 1.10 (0.93-1.30) | Age and sex | |||
505/600 | Minnesota | 1.21 (1.01-1.44) | Age and sex | |||
Ghousaini et al.
| 2008 |
2,299/2,284
|
UK
|
Cases from prospective study at East Anglia
|
1.27 (1.16-1.37)
| Crude |
Lie et al.
| 2008 |
561/721
| USA | Colon cancer cases from SEER Kentucky |
1.69 (1.19-2.40)
| Age, sex, BMI, and NSAID use. |
Cuacasian | 1.61 (1.36-2.30) | Age, sex, BMI, and NSAID use. | ||||
Schafmayer
| 2009 |
2,713/2,718
| Germany | Colorectal cancer cases with German ancestry |
1.22 (1.13-1.31)
| Crude |
Curtin et al.
| 2009 |
1,069/1,040
|
USA/UK
|
Colorectal cancer cases from USA/UK
|
1.17 (1.03-1.32)
| Crude |
Our study
|
481/962
|
Japan
|
HERPACC II participatns (Japanese)
|
1.22 (1.04-1.44)
| Age and sex | |
1.26 (1.06-1.48) | Age, sex, drinking, smoking, BMI, folate consumption, energy, physical exercise, and family history of CRC |