Introduction
Materials and methods
Human subjects
Genotyping
SNP | Gene | Chr | Bp | Alleles | MAF (ASW) | MAF (CEU) | Fst | Functiona
|
---|---|---|---|---|---|---|---|---|
rs116071925 |
CYP27A1
| 2 | 219,646,701 | CA
| 0.016 | 0 | 0.025 | 5′ UTR |
rs115316390 |
GC
| 4 | 72,651,159 | GA
| 0 | 0 | 0.03 | Intronic |
rs1155563 |
GC
| 4 | 72,643,488 | TC
| 0.074 | 0.264 | 0.07 | Ahn et al.; Wang et al. |
rs16847024 |
GC
| 4 | 72,650,679 | CA | 0.074 | 0 | 0.084 | Promoter |
rs17467825 |
GC
| 4 | 72,605,517 | AG
| 0.107 | 0.241 | 0.057 | DGV |
rs2282679 |
GC
| 4 | 72,608,383 | TG
| 0.107 | 0.241 | 0.056 | Wang et al. |
rs2298850 |
GC
| 4 | 72,614,267 | GC
| 0.066 | 0.23 | 0.075 | Wang et al. |
rs3733359 |
GC
| 4 | 72,649,774 | GA
| 0.221 | 0.057 | 0.115 | Intronic_S |
rs3755967 |
GC
| 4 | 72,609,398 | CT
| 0.107 | 0.241 | 0.051 | Wang et al. |
rs7041 |
GC
| 4 | 72,618,334 | AC
| 0.156 | 0.42 | 0.248 | Missense |
rs2740574 |
CYP3A4
| 7 | 99,382,096 | CT
| 0.344 | 0.017 | 0.601 | Promoter |
rs10741657 |
CYP2R1
| 11 | 14,914,878 | GA
| 0.328 | 0.414 | 0.035 | Promoter |
rs114050796 |
CYP2R1
| 11 | 14,914,653 | CT
| 0.066 | 0 | 0.032 | Promoter |
rs12794714 |
CYP2R1
| 11 | 14,913,575 | GA
| 0.164 | 0.431 | 0.118 | Synonymous |
rs1993116 |
CYP2R1
| 11 | 14,910,234 | GA
| 0.32 | 0.425 | 0.039 | Ahn et al.; Wang et al. |
rs2060793 |
CYP2R1
| 11 | 14,915,310 | GA
| 0.41 | 0.408 | 0.01 | Promoter |
rs11234027 |
DHCR7
| 11 | 71,234,107 | GA
| 0.254 | 0.195 | 0.051 | Promoter |
rs12785878 |
DHCR7
| 11 | 71,167,449 | GT
| 0.352 | 0.276 | 0.306 | Wang et al. |
rs12800438 |
DHCR7
| 11 | 71,171,003 | GA
| 0.484 | 0.276 | 0.172 | Wang et al. |
rs3794060 |
DHCR7
| 11 | 71,187,679 | CT
| 0.328 | 0.276 | 0.325 | 5′ UTR |
rs3829251 |
DHCR7
| 11 | 71,194,559 | GA
| 0.18 | 0.178 | 0.026 | Ahn et al. |
rs4944957 |
DHCR7
| 11 | 71,168,035 | GA
| 0.426 | 0.276 | 0.095 | Wang et al. |
rs4945008 |
DHCR7
| 11 | 71,221,248 | AG
| 0.336 | 0.282 | 0.322 | DGV |
rs7944926 |
DHCR7
| 11 | 71,165,625 | AG
| 0.352 | 0.276 | 0.306 | Wang et al. |
rs10877012 |
CYP27B1
| 12 | 58,162,085 | GT
| 0.085 | 0 | – | Promoter |
rs4646537 |
CYP27B1
| 12 | 58,157,281 | TG
| 0.082 | 0.034 | 0.011 | Intronic |
rs11568820 |
VDR
| 12 | 48,302,545 | TC
| 0.295 | 0.236 | 0.409 | Promoter |
rs11574038 |
VDR
| 12 | 48,277,153 | CT
| 0.025 | 0 | 0.024 | Intronic |
rs11574143 |
VDR
| 12 | 48,234,917 | CT
| 0.123 | 0.08 | 0.022 | DGV |
rs1544410 |
VDR
| 12 | 48,239,835 | CT
| 0.27 | 0.489 | 0.023 | Intronic |
rs1989969 |
VDR
| 12 | 48,278,010 | GA
| 0.459 | 0.356 | 0.01 | Intronic |
rs2228570 |
VDR
| 12 | 48,272,895 | GA
| 0.156 | 0.391 | 0.072 | Missense |
rs731236 |
VDR
| 12 | 48,238,757 | AG
| 0.279 | 0.489 | 0.023 | Synonymous |
rs2248359 |
CYP24A1
| 20 | 52,791,518 | TC
| 0.459 | 0.391 | 0.078 | Promoter |
rs2248461 |
CYP24A1
| 20 | 52,792,202 | AG
| 0.467 | 0.362 | 0.084 | Promoter |
rs6013897 |
CYP24A1
| 20 | 52,742,479 | TA
| 0.287 | 0.236 | 0.012 | Wang et al. |
rs6022990 |
CYP24A1
| 20 | 52,775,532 | AG
| 0.098 | 0 | 0.07 | Missense |
rs73913755 |
CYP24A1
| 20 | 52,790,194 | GA
| 0.167 | 0 | – | 5′ UTR |
rs73913757 |
CYP24A1
| 20 | 52,790,518 | CT
| 0.139 | 0 | 0.112 | Promoter |
Statistical analysis
Results
Analysis of all AA CRC cases
Cases | Controls | |
---|---|---|
NCCC study
| ||
Number of subjects | 371 | 380 |
Mean age and SD | 62 ± 10 | 65 ± 6 |
Mean %WAA and SD | 83 ± 13 | 82 ± 15 |
Gender (M/F) | 192/179 | 181/199 |
CCCC study
| ||
Number of subjects | 590 | 458 |
Mean age and SD | 64 ± 13 | 57 ± 13 |
Mean %WAA and SD | 83 ± 16 | 86 ± 16 |
Gender (M/F) | 331/259 | 169/289 |
Pooled study
| ||
Number of subjects | 961 | 838 |
Mean age and SD | 63 ± 12 | 61 ± 13 |
Mean %WAA and SD | 83 ± 14 | 84 ± 15 |
Gender (M/F) | 523/438 | 350/488 |
SNPs | Gene | MA | MAF | Genotype countsa
| OR (95 % CI) |
p value | Adj p
| |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
11 Case | 11 Cont | 12 Case | 12 Cont | 22 Case | 22 Cont | |||||||
rs12794714 |
CYP2R1
| A | 0.183 | 638 (71) | 501 (66) | 253 (28) | 239 (31) | 11 (1.2) | 20 (1.4) | 0.79 (0.65–0.96) | 0.019 | 0.048 |
rs7041 |
GC
| G | 0.196 | 585 (68) | 478 (64) | 234 (27) | 244 (33) | 39 (4.5) | 26 (2) | 0.84 (0.69–1.01) | 0.068 | 0.321 |
rs17467825 |
GC
| G | 0.106 | 774 (84) | 639 (80) | 137 (15) | 150 (19) | 12 (1.3) | 8 (0.5) | 0.81 (0.64–1.03) | 0.079 | 0.407 |
Analysis of AA CRC cases stratified by tumor location
SNPs | Gene | MA | MAF | L-CRC | R-CRC | ||||
---|---|---|---|---|---|---|---|---|---|
OR (95 % CI) |
p value | Adj p
| OR (95 % CI) |
p value | Adj p
| ||||
rs12794714 |
CYP2R1
| A | 0.183 | 0.83 (0.65–1.07) | 0.15 | 0.88 | 0.75 (0.56–1.01) | 0.056 | 0.14 |
rs7041 |
GC
| G | 0.196 | 0.90 (0.71–1.13) | 0.35 | 0.99 | 0.77 (0.58–1.01) | 0.059 | 0.26 |
rs16847024 |
GC
| T | 0.082 | 1.49 (1.08–2.06) | 0.015 | 0.091 | 0.92 (0.61–1.37) | 0.670 | 1 |
rs6022990 |
CYP24A1
| G | 0.093 | 1.40 (1.06–1.86) | 0.018 | 0.087 | 0.94 (0.64–1.37) | 0.730 | 1 |
rs73913757 |
CYP24A1
| T | 0.183 | 0.81 (0.65–1.01) | 0.055 | 0.238 | 0.97 (0.75–1.27) | 0.830 | 1 |
rs17467825 |
GC
| G | 0.106 | 0.77 (0.58–1.04) | 0.085 | 0.374 | 0.87 (0.61–1.22) | 0.420 | 1 |