Table 2.
Incidence of CRC, overall and by intraepithelial and stroma T-cell subset density, according to coffee intake in the combined cohorts of the NHS (1980-2012) and HPFS (1986-2012)
| Characteristics | Coffee intake, cups/d |
P trend a | P heterogeneity b | |||
|---|---|---|---|---|---|---|
| 0 | <1 | 1-3 | ≥3 | |||
| Overall | ||||||
| Person-years | 402 273 | 604 468 | 1 712 111 | 866 168 | ||
| Cases (n = 3161), No. | 269 | 579 | 1621 | 692 | ||
| HR (95% CI)c | 1 (Referent) | 1.08 (0.94 to 1.26) | 1.08 (0.94 to 1.23) | 0.99 (0.89 to 1.15) | .22 | |
| Intraepithelial | ||||||
| CD3+CD4+FOXP3+ cells | ||||||
| Low density (n = 625), No. | 48 | 110 | 328 | 139 | ||
| HR (95% CI)c | 1 (Referent) | 1.23 (0.87 to 1.73) | 1.26 (0.93 to 1.72) | 1.11 (0.79 to 1.55) | .68 | .39 |
| Intermediate density (n = 142), No. | 11 | 18 | 79 | 34 | ||
| HR (95% CI)c | 1 (Referent) | 0.79 (0.38 to 1.63) | 1.29 (0.70 to 2.36) | 1.05 (0.54 to 2.04) | .50 | |
| High density (n = 141), No. | 17 | 26 | 71 | 27 | ||
| HR (95% CI)c | 1 (Referent) | 0.68 (0.37 to 1.26) | 0.62 (0.36 to 1.07) | 0.53 (0.29 to 0.98) | .099 | |
| CD3+CD4+CD45RO+ cells | ||||||
| Low density (n = 302), No. | 28 | 48 | 161 | 65 | ||
| HR (95% CI)c | 1 (Referent) | 1.04 (0.65 to 1.67) | 1.11 (0.74 to 1.67) | 0.92 (0.58 to 1.44) | .94 | .71 |
| Intermediate density (n = 305), No. | 27 | 51 | 159 | 68 | ||
| HR (95% CI)c | 1 (Referent) | 0.92 (0.58 to 1.45) | 1.06 (0.71 to 1.60) | 0.91 (0.58 to 1.43) | .76 | |
| High density (n = 301), No. | 21 | 55 | 158 | 67 | ||
| HR (95% CI)c | 1 (Referent) | 1.16 (0.70 to 1.92) | 1.17 (0.74 to 1.86) | 1.07 (0.65 to 1.76) | .81 | |
| CD3+CD4+CD45RO− cells | ||||||
| Low density (n = 514), No. | 41 | 94 | 264 | 115 | ||
| HR (95% CI)c | 1 (Referent) | 1.22 (0.85 to 1.77) | 1.17 (0.84 to 1.63) | 1.05 (0.73 to 1.52) | .47 | .72 |
| Intermediate density (n = 197), No. | 16 | 21 | 115 | 45 | ||
| HR (95% CI)c | 1 (Referent) | 0.69 (0.36 to 1.30) | 1.38 (0.83 to 2.31) | 1.06 (0.60 to 1.87) | .31 | |
| High density (n = 197), No. | 19 | 39 | 99 | 40 | ||
| HR (95% CI)c | 1 (Referent) | 0.92 (0.53 to 1.60) | 0.80 (0.49 to 1.32) | 0.71 (0.41 to 1.23) | .17 | |
| CD3+CD8+CD45RO+ cells | ||||||
| Low density (n = 423), No. | 37 | 87 | 206 | 93 | ||
| HR (95% CI)c | 1 (Referent) | 1.26 (0.86 to 1.86) | 1.06 (0.74 to 1.51) | 0.96 (0.65 to 1.42) | .15 | .39 |
| Intermediate density (n = 242), No. | 20 | 25 | 144 | 53 | ||
| HR (95% CI)c | 1 (Referent) | 0.62 (0.35 to 1.12) | 1.26 (0.80 to 2.00) | 0.96 (0.57 to 1.59) | .39 | |
| High density (n = 243), No. | 19 | 42 | 128 | 54 | ||
| HR (95% CI)c | 1 (Referent) | 1.03 (0.59 to 1.77) | 1.06 (0.65 to 1.73) | 0.97 (0.57 to 1.66) | .77 | |
| CD3+CD8+CD45RO− cells | ||||||
| Low density (n = 571), No. | 43 | 107 | 295 | 126 | ||
| HR (95% CI)c | 1 (Referent) | 1.29 (0.90 to 1.84) | 1.29 (0.93 to 1.79) | 1.11 (0.78 to 1.58) | .55 | .51 |
| Intermediate density (n = 168), No. | 20 | 28 | 88 | 32 | ||
| HR (95% CI)c | 1 (Referent) | 0.71 (0.40 to 1.26) | 0.72 (0.44 to 1.16) | 0.59 (0.34 to 1.03) | .16 | |
| High density (n = 169), No. | 13 | 19 | 95 | 42 | ||
| HR (95% CI)c | 1 (Referent) | 0.72 (0.35 to 1.48) | 1.15 (0.63 to 2.09) | 1.04 (0.55 to 1.99) | .42 | |
| Stroma | ||||||
| CD3+CD4+FOXP3+ cells | ||||||
| Low density (n = 485), No. | 43 | 81 | 253 | 108 | ||
| HR (95% CI)c | 1 (Referent) | 1.00 (0.69 to 1.45) | 1.07 (0.77 to 1.49) | 0.91 (0.63 to 1.30) | .38 | .80 |
| Intermediate density (n = 211), No. | 14 | 34 | 111 | 52 | ||
| HR (95% CI)c | 1 (Referent) | 1.18 (0.63 to 2.19) | 1.40 (0.80 to 2.45) | 1.39 (0.77 to 2.53) | .29 | |
| High density (n = 211), No. | 19 | 39 | 113 | 40 | ||
| HR (95% CI)c | 1 (Referent) | 0.99 (0.57 to 1.72) | 0.98 (0.60 to 1.60) | 0.77 (0.44 to 1.33) | .19 | |
| CD3+CD4+CD45RO+ cells | ||||||
| Low density (n = 302), No. | 26 | 52 | 148 | 76 | ||
| HR (95% CI)c | 1 (Referent) | 1.10 (0.68 to 1.77) | 1.03 (0.68 to 1.57) | 1.08 (0.69 to 1.71) | .93 | .51 |
| Intermediate density (n = 304), No. | 28 | 47 | 167 | 62 | ||
| HR (95% CI)c | 1 (Referent) | 0.86 (0.54 to 1.37) | 1.10 (0.73 to 1.64) | 0.85 (0.54 to 1.34) | .62 | |
| High density (n=301), No. | 22 | 55 | 162 | 62 | ||
| HR (95% CI)c | 1 (Referent) | 1.17 (0.71 to 1.92) | 1.22 (0.77 to 1.91) | 0.97 (0.59 to 1.59) | .38 | |
| CD3+CD4+CD45RO- cells | ||||||
| Low density (n = 365), No. | 31 | 64 | 190 | 80 | ||
| HR (95% CI)c | 1 (Referent) | 1.04 (0.68 to 1.59) | 1.06 (0.73 to 1.55) | 0.92 (0.60 to 1.39) | .41 | .74 |
| Intermediate density (n = 270), No. | 22 | 37 | 146 | 65 | ||
| HR (95% CI)c | 1 (Referent) | 0.86 (0.50 to 1.46) | 1.21 (0.77 to 1.91) | 1.11 (0.68 to 1.83) | .33 | |
| High density (n = 272), No. | 23 | 53 | 141 | 55 | ||
| HR (95% CI)c | 1 (Referent) | 1.19 (0.73 to 1.95) | 1.09 (0.69 to 1.70) | 0.88 (0.54 to 1.45) | .18 | |
| CD3+CD8+CD45RO+ cells | ||||||
| Low density (n = 383), No. | 32 | 74 | 185 | 92 | ||
| HR (95% CI)c | 1 (Referent) | 1.30 (0.85 to 1.97) | 1.11 (0.76 to 1.63) | 1.06 (0.70 to 1.60) | .42 | .75 |
| Intermediate density (n = 262), No. | 18 | 40 | 147 | 57 | ||
| HR (95% CI)c | 1 (Referent) | 1.04 (0.59 to 1.82) | 1.45 (0.88 to 2.37) | 1.28 (0.75 to 2.18) | .28 | |
| High density (n = 262), No. | 26 | 40 | 145 | 51 | ||
| HR (95% CI)c | 1 (Referent) | 0.75 (0.46 to 1.21) | 0.90 (0.59 to 1.37) | 0.67 (0.42 to 1.08) | .19 | |
| CD3+CD8+CD45RO− cells | ||||||
| Low density (n = 503), No. | 37 | 94 | 254 | 118 | ||
| HR (95% CI)c | 1 (Referent) | 1.35 (0.92 to 1.99) | 1.29 (0.91 to 1.83) | 1.20 (0.82 to 1.76) | .83 | .94 |
| Intermediate density (n = 202), No. | 19 | 32 | 121 | 30 | ||
| HR (95% CI)c | 1 (Referent) | 0.80 (0.46 to 1.39) | 1.05 (0.65 to 1.70) | 0.58 (0.33 to 1.03) | .070 | |
| High density (n = 202), No. | 20 | 28 | 102 | 52 | ||
| HR (95% CI)c | 1 (Referent) | 0.70 (0.40 to 1.24) | 0.86 (0.53 to 1.41) | 0.89 (0.53 to 1.51) | .69 | |
Trend test was performed using the median intake of each category. CI = confidence interval; CRC = colorectal cancer; HPFS = Health Professionals Follow-up Study; HR = hazard ratio; METS = metabolic equivalent task score; NHS = Nurses’ Health Study.
The meta-regression method with a subtype-specific random effect term was used to evaluate the heterogeneity.
Cox proportional hazards model was used with stratification by age, sex (ie, cohort), and calendar year of current questionnaire cycle. We additionally adjusted for family history of CRC, history of diabetes, history of endoscopy, pack-years of smoking (0, 0 to <5, 5 to <20, 20 to <40, and ≥40), body mass index (quartiles), physical activity (METS, quartiles), multivitamin use, regular use of aspirin, regular use of nonsteroidal antiinflammatory drugs, alcohol consumption (0 to <5, 5 to <15, 15 to <30, ≥30 g/d), total calorie intake (quartiles), total red meat intake (quartiles), folate intake (quartiles), calcium intake (quartiles), and Alternative Healthy Eating Index (quartiles). For women, we further adjusted for menopause status and menopausal hormone therapy (premenopause vs postmenopause with never, past, or current use of menopausal hormone therapy).