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. Author manuscript; available in PMC: 2018 Sep 18.
Published in final edited form as: Annu Rev Nutr. 2017 Aug 21;37:293–320. doi: 10.1146/annurev-nutr-071715-051004

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

a

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.

b

Based on nutrient evidence and genetic evidence scores.

c

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.

d

The overall plausibility of interaction was examined by comparing the prior score and the score based on the strength of the observed evidence.

e

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.