Table 5.
Incidence of Colorectal Cancer by pks+ E. coli Status in Relation to Cumulative Average Western Diet Score in the Health Professionals Follow-up Study (1986–2014) and the Nurses’ Health Study (1980–2014)
| Western diet score | P for trend* | P for heterogeneity† | |||
|---|---|---|---|---|---|
| Tertile 1 | Tertile 2 | Tertile 3 | |||
| Health Professionals Follow-up Study (men) | |||||
| Person-Years | 365,506 | 365,602 | 365,680 | ||
| pks+ E. coli status | 0.71 | ||||
| pks+ E. coli negative | |||||
| Cases, No. (total n=476) | 156 | 158 | 162 | ||
| Age-adjusted HR (95% CI)§ | 1 (referent) | 1.19 (0.95–1.50) | 1.41 (1.09–1.82) | <0.001 | |
| Multivariable HR (95% CI)‖ | 1 (referent) | 1.12 (0.89–1.42) | 1.26 (0.96–1.65) | 0.015 | |
| pks+ E. coli positive | |||||
| Cases, No. (total n=43) | 10 | 15 | 18 | ||
| Age-adjusted HR (95% CI)§ | 1 (referent) | 1.77 (0.80–3.95) | 2.33 (1.05–5.14) | 0.042 | |
| Multivariable HR (95% CI)‖ | 1 (referent) | 1.62 (0.72–3.61) | 2.05 (0.93–4.50) | 0.10 | |
| Nurses’ Health Study (women) | |||||
| Person-years | 889,524 | 888,957 | 890,911 | ||
| pks+ E. coli status | 0.018 | ||||
| pks+ E. coli negative | |||||
| Cases, No. (total n=588) | 208 | 196 | 184 | ||
| Age-adjusted HR (95% CI)§ | 1 (referent) | 0.95 (0.75–1.20) | 1.18 (0.87–1.61) | 0.28 | |
| Multivariable HR (95% CI)‖ | 1 (referent) | 0.89 (0.70–1.13) | 1.03 (0.75–1.41) | 0.90 | |
| pks+ E. coli positive | |||||
| Cases, No. (total n=68) | 18 | 22 | 28 | ||
| Age-adjusted HR (95% CI)§ | 1 (referent) | 1.17 (0.59–2.31) | 2.09 (1.07–4.09) | 0.019 | |
| Multivariable HR (95% CI)‖ | 1 (referent) | 1.10 (0.55–2.18) | 1.81 (0.92–3.54) | 0.058 | |
The trend test was performed using the western diet score as a continuous variable with cohort-specific ceilings at 10th and 90th percentiles in the regression model. The 90th and 10th percentile values were used for scores above 90th percentile and those below the 10th percentile, respectively, to eliminate outlier effects.
The meta-regression method with a subtype-specific random effect term was used to test whether the association has a trend across the ordinal subtypes (negative vs. low vs. high) in the multivariable-adjusted model, where the western diet score was used as a continuous variable with cohort-specific ceilings at 10th and 90th percentiles.
Duplication-method Cox proportional hazards model weighted by inverse probabilities based on tissue bacterial data availability for competing risks data was used with total caloric intake adjusted and stratification by age (in months) and year of questionnaire return.
Additionally adjusted for body mass index (continuous with 35 kg/m2 ceiling), cumulative pack-years smoked (continuous with 50 pack-years ceiling), family history of colorectal cancer in any first-degree relative (yes vs. no), previous lower gastrointestinal endoscopy (yes vs. no), physical activity (continuous with a ceiling at 50 metabolic equivalent task score-hours per week), regular use of aspirin or nonsteroidal anti-inflammatory drugs (>2 tablets/week: yes vs. no), multivitamin use (yes vs. no), and alcohol consumption (continuous with 30 g/day ceiling). We additionally adjusted for postmenopausal hormone use (yes vs. no) for the Nurses’ Health Study analysis.
Abbreviations: CI, confidence interval; HR, hazard ratio.