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. 2019 Jan 16;145(9):2315–2329. doi: 10.1002/ijc.32057

Table 2.

Evaluation of environmental main effects for the environmental exposures identified in the selected G×E interactions

Environmental exposure Reference Unit of comparison Number of cases Number of studies Relative risk (95% CI) p Value Prediction interval Heterogeneity (I 2 and/or p value) Evidence class1
Processed meat WCRF, CUP 2017 Per 50 g/day 10,738 10 1.16 (1.08, 1.26) 0.0002 NA I 2 = 20.1%;
p = 0.258
III
Red meat WCRF, CUP 2017 Per 100 g/day 6,662 8 1.12 (1.00, 1.25) 0.05 NA I 2 = 23.6%;
p = 0.241
IV
Light‐to‐moderate alcohol intake WCRF, CUP 2017 1 drink/day 36,942 8 1.06 (1.00, 1.11) 0.03 NA I 2 = 60.4%;
p = 0.013
IV
Vegetables WCRF, CUP 2017 100 g/day 14,136 11 0.98 (0.96, 0.99) 0.01 NA I 2 = 0.0%;
p = 0.48
IV
Total folate WCRF, CUP 2017 100 mcg/day 4,633 8 0.99 (0.98, 1.00) 0.05 NA I 2 = 0.0%;
p = 0.92
IV
Aspirin use Qiao Y, 2018 Users vs. non‐users 151,367 39 0.79 (0.74, 0.85) 7.8×10−11 NA I 2 = 91.1%;
p = 0.000
II2
Aspirin and/or NSAID use Nan H, 2015 Regular users of aspirin, NSAIDs or both vs. non‐regular users 8,634 10 0.69 (0.64, 0.74) 6.20×10−28 NA p = 0.02 II2
Use of estrogen plus progestogen therapy Lin KJ, 2012 Ever users vs. non‐users NR 17 0.74 (0.68, 0.81) <0.001 NA I 2 = 0%;
p = 0.88
III
Overweight WCRF, CUP 2017 Per 5 kg/m2 increase in BMI 71,089 (total number) 38 (20 for men and 24 for women) Men: 1.08 (1.04, 1.11);
women: 1.05 (1.02, 1.08)
Men: p < 0.001
Women: p < 0.001
NA Men: I 2 = 83.3%,
p < 0.001;
women:
I 2 = 82.5%,
p < 0.001
Men: III;
Women: III

Abbreviations: BMI, body mass index; CI, confidence interval; CUP, Continuous Update Project; G×E, gene–environment; NA, not applicable; NR, not reported; NSAID, nonsteroidal anti‐inflammatory drug; vs., versus; WCRF, World Cancer Research Fund.

1

Evidence class was decided using the after criteria: Convincing evidence (class I) required >1,000 cases, highly significant summary associations (p < 10−6 by random effects), a 95% prediction interval not including the null, no evidence of small‐study effects, no evidence of excess significance bias, and low heterogeneity values (I 2 < 50%). Highly suggestive evidence (class II) required >1,000 cases, highly significant summary associations (p < 10−6 by random effects), and the largest study to have a 95% confidence interval that excluded 1. Suggestive evidence (class III) required only >1,000 cases and p < 0.001 by random effects. Evidence was considered weak (class IV) when p < 0.05. No association indicates evidence for the main environmental effects with p > 0.05.

2

The evidence was classified as highly suggestive (class II) due to the high heterogeneity between the studies.