Table 1. Gene-gene interactions in gastrointestinal cancer susceptibility.
| Gene 1 | Gene 2 | Cancer | n (case/control) | ||||
|---|---|---|---|---|---|---|---|
| Gene name (variation)a | ORb | Gene name (variation)a | ORb | ORcombinedb | ORinteractionc | typed | ethnicity [reference]e |
| Interaction between cancer-associated gene variations | |||||||
| PARP1 (p.Val762Ala) | 2.17 | XRCC1 (p.Arg399Gln) | 1.61 | 6.43 | 1.84 | GC | 500/1000 Chinese [17] |
| ADH1B (p.Arg47His) | (3.34) | ALDH2 (p.Glu504Lys) | (2.51) | 13.46 (8.08) | 1.60' (0.96) | EC | 4220/8946 Asian [30] |
| ADH1B (p.Arg47His) | 1.85 | ALDH2 (p.Glu504Lys) | 1.66 | 6.79 | 2.21 | EC | 1070/2836 Japanese [29] |
| MDM2 (rs2279744 T>G) | 1.94 | TP53 (p.Arg72Pro) | 1.72 | 5.05 | 1.51 | GC | 500/1000 Chinese [59] |
| MUTYH (p.Gln324His) | 3.35 | OGG1 (p.Ser326Cys) | 1.83 | 8.31 | 1.36 | CRC | 182/200 Polish [9] |
| XRCC1 (p.Arg399Gln) | 2.03 | OGG1 (p.Ser326Cys) | 1.83 | 4.97 | 1.34 | CRC | 182/200 Polish [9] |
| TP53 (p.Arg72Pro) | (1.78) | MDM2 (rs2279744 T>G) | (1.46) | 3.10 | 1.19' | EC | 758/1420 Chinese [58] |
| CHEK2 (quadruple)f | (1.38) | CDKN1B (p.Val109Gly) | (1.34) | (2.14) | (1.16) | CC | 872/3812 Polish [72] |
| TPH2 (rs10879357 G>A) | (1.22) | CASC20 (rs1571218 G>T) | (1.20) | 1.63 (1.55) | 1.11' (1.06) | CRC | 10907/13216 mixed [81] |
| SMAD7 (rs11874392 T>A) | 1.47 | TGFBR1 (rs6478972 A>G) | 1.38 | 1.44 (1.50) | 0.71 (0.74) | CRC | 794/842 Chinese [69] |
| Interaction between cancer-associated and non-associated gene variations | |||||||
| CYP1A1 (p.Ile462Val) | (2.87) | CYP2E1 (rs2031920 C>T)g | (1.62) | (11.25) | (1.85) | EC | 526/526 Kashmir [48] |
| PRKAG2 (rs1104897 G>A) | (1.30) | RPS6KB1 (rs180515 A>G) | (1.05) | (1.63) | (1.19) | RC | 791/999 mixedh[73] |
| NQO1 (p.Pro187Ser) | 6.65 | NQO2 (rs2070999 G>A) | 1.48 | 11.41 | 1.16 | EC | 135/195 Kashmiri [37] |
| MUTYH (p.Gln324His) | (4.05) | XRCC1 (p.Arg194Trp) | (1.24) | (5.65) | (1.13) | CRC | 182/200 Polish [9] |
| GSTT1 (Δ) | (1.81) | APEX1 (p.Asp148Glu) | (1.21) | 1.84 | 0.84' | GC | 314/548 Italian [23] |
| PIK3CA (rs7640662 C>G) | (1.31) | RPS6KB1 (rs180519 G>A) | (1.13) | (1.19) | (0.80) | RC | 791/999 mixedh [73] |
| GSTM1 (Δ) and GSTT1 (Δ) | (2.50) | APEX1 (p.Asp148Glu) | (1.21) | 2.32 | 0.77' | GC | 314/548 Italian [23] |
| GSTM1 (Δ) | (2.24) | NAT2 (p.Arg197Gln) | (1.81) | (2.82) | (0.70) | CRC | 150/162 Romanian [45] |
| PARP1 (p.Val762Ala) | (2.19) | MMP2 (rs243865 C>T) | (1.05) | (1.38) | (0.60) | GC | 59/320 Korean [79] |
| OGG1 (p.Ser326Cys) | (1.71) | XRCC1 (p.Arg194Trp) | (1.22) | (0.92) | (0.44) | CRC | 182/200 Polish [9] |
| Interaction between non-associated gene variations | |||||||
| XPC (PAT S>L) | (1.20) | XPA (rs1800975 G>A) | (1.02) | 2.15 (1.55) | 1.76' (1.27) | GC | 314/548 Italian [23] |
| MDM2 (rs2279744 T>G) | (1.11) | TP53 (p.Arg72Pro) | (1.06) | 1.78 (1.76) | 1.52' (1.50) | CRC | 444/569 Han Chinese [57] |
The interacting gene variant pairs are listed in descending order of ORinteraction value, shown in the sixth column. Nonsynonymous SNPs are denoted by the encoded amino acid changes, while the other variations are denoted by the reference SNP (rs) numbers. Risk-associated alleles that are more frequent in cancer cases than in healthy controls are shown in bold.
Odds ratios (ORs) of the risk-associated alleles for cancer susceptibility are shown. ORs of non-significant associations are italicized. If the publication presented OR of non-risk allele rather than risk allele, crude OR of risk allele was calculated using the χ2 test and is shown here in parenthesis.
ORinteraction = ORcombined ÷ (OR1 × OR2). When an adjusted ORinteraction value was not reported in the publication, OR'interaction (marked with a prime) was calculated using the reported adjusted ORcombined and the crude OR1 and OR2 that were calculated using the reported genotype data. Alternatively, crude ORinteraction values were calculated using crude ORcombined, OR1 and OR2 values and are parenthesized here.
CC = colon cancer, CRC = colorectal cancer, EC = esophageal cancer, GC = gastric cancer, RC = rectal cancer.
Criteria for publication search and study selection. This review included only studies where ORinteraction shown in the sixth column is >1.10 or <0.91. A search for articles in PubMed, Google Scholar and Web of Science, published through July 8, 2015, was conducted using the following keywords: ‘epistasis’ or ‘gene-gene interaction’ or ‘epistatic interaction’; and ‘esophageal cancer’ or ‘gastric cancer’ or ‘colorectal cancer’ or 'colon cancer' or 'rectal cancer' or ‘intestine cancer’.
The quadruple variation of CHEK2 includes del5395, 1100delC, c.444+1G>A and I157T [72].
Only rs2031920 (C>T) of CYP2E1, perfectly correlated (r2 = 1) with rs3813867 (G>C), is shown here [48].
The mixed population includes non-Hispanic Caucasians, Hispanics, American Indians, African Americans and Asians [73].