Table 4.
Phase I/II metabolic activation/detoxification and DNA repair genes in NPC
| Author/Yr | Country | Sample Size (#Cases/#Ctrls) |
Genes Targeted | Methods/Approach | Polymorphic Site(s) Evaluated (Significant Association Reported – Yes/No) |
|---|---|---|---|---|---|
| Phase I/II Metabolic Activation/Detoxification Genes | |||||
| Cheng69 (2003) | Taiwan | 337/317 | CYP1A1 | PCR-RFLP/Candidate | m1/m2 (No) |
| Guo19 (2010) | China | Discovery: 358/629 Validation: 213/230 |
CYP2E1 | TaqMan PCR & SBT/Candidate | rs2031920 (No) rs6413432 (No) |
| Jia20 (2009) | China | Discovery: 2,499 individuals (w/in 546 families) Validation: 755/755 |
CYP2E1 | TaqMan PCR/Tag-SNPs | rs915906 (No)* rs915908 (No) rs1536826 (No)* rs2249695 (No)* rs3813865 (No)* rs3827688 (No)* rs8192780 (No)* rs9418990 (No)* |
| Yang70 (2005) | Taiwan | 103/553 | CYP2E1 | PCR-RFLP/Candidate | c2 (No) |
|
Kongruttanachok71 (2001) |
Thailand | 217/297 | CYP2E1 | PCR-RFLP/Candidate | rs2031920 (Yes) |
| He72 (2009) | China | 225/273 100/100 |
GSTM1 | PCR-ARMS/Candidate Sequencing/Candidate |
1270533T/G (No) C1256088C (No) |
| Guo73 (2008) | China | 350/622 | GSTM1 | PCR-electrophoresis/Candidate | Non-null/null (No) |
| Cheng69 (2003) | Taiwan | 337/317 | GSTM1 | PCR-RFLP/Candidate | Non-null/null (No) |
| Cheng69 (2003) | Taiwan | 337/317 | GSTP1 | PCR-RFLP/Candidate | 1a/1b (No) |
| Guo19 (2010) | China | Discovery: 358/629 Validation: 213/230 |
GSTP1 | TaqMan PCR/Candidate | rs947894 (No) |
| Guo73 (2008) | China | 350/622 | GSTT1 | PCR-electrophoresis/Candidate | Non-null/null (No) |
| Cheng69 (2003) | Taiwan | 337/317 | GSTT1 | PCR-RFLP/Candidate | Non-null/null (No) |
| Guo19 (2010) | China | Discovery: 358/629 Validation: 213/230 |
MPO | TaqMan PCR /Candidate | rs2333227 (No) |
| Cheng69 (2003) | Taiwan | 337/317 | NAT2 | PCR-RFLP/Candidate | Slow/fast (No) |
| Guo19 (2010) | China | Discovery: 358/629 Validation: 213/230 |
NQO1 | PCR-RFLP/Candidate | rs1800566 (No) |
| DNA Repair Genes | |||||
| Qin21 (2011) | China | Discovery stage: 755/755 Validation stage: 1568/1297 |
88 genes** | Illumina GoldenGate/ Tag-SNPs |
RAD51L1*: rs927220 (Yes) rs11158728 (Yes) |
| Yang74 (2009) | China | 267/304 | ERCC1 | PCR-RFLP/Candidate | rs11615 (No) rs3212986 (Yes) |
| Zheng75 (2011) | China | 1052/1168 | NBS1 | PCR-RFLP/Candidate | rs1805794 (Yes) rs2735383 (No) |
| Cho76 (2003) | Taiwan | 334/283 | hOGG1 | PCR-RFLP/Candidate | Ser326Cys (Yes) |
| Laantri77 (2011) | Morocco Algeria Tunisia |
598/545 | hOGG1 | TaqMan PCR/Candidate | Ser326Cys (No) |
| Yang78 (2008) | China | 153/168 | XPC | PCR-RFLP/Candidate | Val499 Ala (Yes) Lys939Gln (No) Poly-AT (No) |
| Yang79 (2007) | China | 153/168 | XPD | PCR-RFLP/Candidate | Lys751Gln (Yes) |
| Laantri77 (2011) | Morocco Algeria Tunisia |
598/545 | XRCC1 | TaqMan PCR/Candidate | Arg194Trp (No) Arg280His (No) Arg399Gln (No) |
| Yang79 (2007) | China | 153/168 | XRCC1 | PCR-RFLP/Candidate | Arg194Trp (Yes)*** Arg280His (No) Arg399Gln (No) |
| Cao80 (2006) | China | 462/511 | XRCC1 | PCR-RFLP/Candidate | Arg194Trp (Yes)*** Arg399Gln (No) |
| Cho76 (2003) | Taiwan | 334/283 | XRCC1 | PCR-RFLP/Candidate | Arg280His (Yes) Arg399Gln(No) |
| Yang79 (2007) | China | 153/168 | XRCC3 | PCR-RFLP/Candidate | Thr241Met (No) |
PCR-ARMS (amplification refractory mutation system), CYP (Cytochrome), GST (Glutathione S-transferase), MPO (Myeloperoxidase), NAT2 (N-acetyltransferase gene 2), NQO1 (NAD(P)H dehydrogenase, quinone 1), RFLP (Restriction fragment length polymorphism), ERCC1 (excision repair cross complementing group 1), hOGG1 (human 8-oxoguanine DNA glycosylase 1), NBS1 (Nijmegen breakage syndrome 1), XPD (xeroderma pigmentosum group D), XPC (xeroderma pigmentosum group C), XRCC1 and XRCC3 (X-ray repair cross-complementing groups 1 and 3).
Significant effects were noted in sub-analyses restricted to young smokers.
For complete list of 676 Tag-SNPs within 88 DNA repair genes evaluated in the discovery stage and 11 SNPs within 7 DNA repair genes that were significant in the discovery stage and evaluated in the replication stage, refer to reference #21.
While the studies by Yang and Cao both reported evidence for a significant association between XRCC1 codon 194 polymorphism and NPC risk, the reported associations were in opposite directions.