Table I.
Polymorphisms in selected polycyclic aromatic amine metabolizing genes and their effect on enzyme function
| Variant (alleles)a,b | Risk allele frequencyc | Amino acid change | Effect of risk allele on metabolizing enzymatic activity | |
|---|---|---|---|---|
| Phase I enzymes | ||||
| AHR | rs2066853(G/A) | 0.183 | R554K | Higher inducibility (12) |
| CYP1A2 | rs762551 (C/A) | 0.716 | NA | Increasing enzymatic activity (45) |
| CYP1B1 | rs1056836 (G/C) | 0.532 | V432L | Increasing mRNA expression (46) |
| rs1800440 (A/G) | 0.827 | N453S | Increasing enzymatic activity (47) | |
| CYP2C9 | rs28371674 (C/T) | 0.118 | R144C | Increasing enzymatic activity (48)d |
| rs1057910 (A/C) | 0.059 | I359L | Increasing enzymatic activity (49)d | |
| CYP2E1 | rs2031920 (C/T) | 0.022 | NA | Increasing enzymatic activity by enhancing the transcription (50,51) |
| Phase II enzymes | ||||
| NAT1 e | rs4986782 (G/A) | 0.017 | R187Q | Slow acetylation; Decreasing enzymatic activity (52) |
| rs5030839 (C/T) | 0.003 | R187X | Slow acetylation; Decreasing enzymatic activity (52) | |
| NAT2 e | rs1041983 (C/T) | 0.335 | Y94Y | The combined effect of all 7 SNPs were categorized to slow acetylation(reference), intermediate acetylation and rapid acetylation (Increasing enzymatic activity) (52,53) |
| rs1208 (G/A) | 0.426 | R268K | ||
| rs1799929 (C/T) | 0.409 | L161L | ||
| rs1799930 (G/A) | 0.711 | R197Q | ||
| rs1799931 (G/A) | 0.048 | G286E | ||
| rs1801279 (G/A) | 0.008 | R64Q | ||
| rs1801280 (T/C) | 0.570 | I114T | ||
| EPHX1 | rs1051740 (T/C) | 0.290 | T213H | Decreasing enzymatic activity (54) |
| SULT1A1 | rs9282861 (G/A) | 0.236 | R213H | Decreasing enzymatic activity (55,56) |
| UGT1A7 | rs61261057 (G/A) | 0.002 | G115S | Decreasing enzymatic activity (57) |
| GSTM1 | Homozygous deletion | 0.089 | Null | Depleted enzymatic activity (58,59) |
| GSTT1 | Homozygous deletion | 0.145 | Null | Depleted enzymatic activity (59) |
aDatabase of SNPs (http://www.ncbi.nlm.nih.gov/SNP/).
bRisk allele is highlighted in bold.
cFrequency of the minor allele among controls in the TCPS.
dDatabase of SNPs (http://www.cypalleles.ki.se/cyp2c9.htm).
eDatabase of SNPs (http://louisville.edu/medschool/pharmacology/nat/). Details for phenotype imputation shown in Supplementary Appendices 3 and 4, available at Carcinogenesis Online.