Table 2. Evaluation of evidence of gene-environment interactions for the five major cancers.
Nutrient/food | Genetic variant | Gene (or near gene) | Score for nutrient evidence | Score for genetic evidence/Venice criteria | Prior score b | Score based on observed evidence c | Combined Score d |
---|---|---|---|---|---|---|---|
BREAST CANCER | |||||||
Alcohol | rs4880 | MnSOD | Class II | NS | Weak - 3 | CCC | No evidence |
rs17468277/rs1045485 a | CASP8 | Class II | NS | Weak - 3 | CBC/CCC | No evidence | |
rs2853826 (A10398G) | ND3 | Class II | NS | Weak - 3 | C-C | No evidence | |
rs698 | ADH1C | Class II | NS | Weak - 3 | --C | Not possible to evaluate | |
Carotenoids | rs2333227 (G463A) | MPO | Class III | NS | Weak - 3 | BBC | No evidence |
COLORECTAL CANCER | |||||||
Alcohol | rs1805087 (A2756G) | MTR | Class I | NS | Weak - 3 | -BB | Weak evidence |
rs1042522 (Pro72Arg) | p53 | Class I | NS | Weak - 3 | --C | No evidence | |
Vegetables | rs16892766 | 8q23.3 | Class III | Strong/AAA | Moderate - 2 | CBB | Weak evidence |
Cruciferous vegetables | Present/null | GSTM1 and GSTT1 | NA; class III for vegetables | NSe | Weak - 3 | -CB | No evidence |
Present/null | GSTM1 | NSe | Weak - 3 | -CB | No evidence | ||
Present/null | GSTT1 | NSe | Weak - 3 | -CB | Weak evidence | ||
Processed meat | rs4143094 | 10p14 | Class III | NS | Weak - 3 | BBB | Moderate evidence |
NS – non significant (p value <10-5) evidence for the main genetic effects
rs17468277 and rs1045485 variants are in linkage disequilibrium and have r2=1 and D’=1 in HapMap European populations. Both variants are often used interchangeable in genetic association studies and meta-analyses. rs17468277 – alcohol interaction was classified as week evidence in the combined score, however a later and bigger meta-analysis by Barrdahl M et al. (2014) did not observed any interaction with the correlated rs1045485 variant. Therefore, combined score for CASP8 – alcohol interaction was set to no evidence.
Based on nutrient evidence and genetic evidence scores.
The strength of the observed evidence for interaction between the dietary exposure and the genetic variants was based on an extension of the HuGENet Venice criteria used for assessing cumulative evidence for genetic associations. Each gene-diet association was graded based on the amount of evidence, the extent of replication and protection of bias.
The overall plausibility of interaction was examined by comparing the prior score and the score based on the strength of the observed evidence.
The effect of GSTM1 and GSTT1 deletion polymorphisms reached nominal significance (p<0.05), but did not reach p<10-5 which was used to declare significant association in the present review.