Table 3.
Intake of dietary calcium, dairy calcium and calcium supplement and risk of colorectal cancer according to tumor CASR expression in the Nurses’ Health Study (1980–2012) and Health Professionals Follow-up Study (1986–2012)
| Dietary calcium intake (mg/day)
|
||||||
|---|---|---|---|---|---|---|
| <600 | 600–749 | 750–899 | ≥900 | Ptrend* | Pheterogeneity¶ | |
| Total colorectal cancer | ||||||
| Person-years(n=3,662,980) | 1,006,102 | 1,018,371 | 769,798 | 868,709 | ||
| No. cases (n=779) | 211 | 230 | 168 | 170 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.96 (0.80 to 1.16) | 0.90 (0.73 to 1.10) | 0.78 (0.64 to 0.96) | 0.01 | |
| Multivariable HR (95%CI) § | 1 (ref) | 0.97 (0.80 to 1.18) | 0.92 (0.74 to 1.14) | 0.83 (0.66 to 1.04) | 0.07 | |
|
| ||||||
| CASR | ||||||
| No/weak | ||||||
| No. cases (n=150) | 42 | 31 | 31 | 46 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.63 (0.40 to 1.01) | 0.81 (0.50 to 1.30) | 1.02 (0.66 to 1.56) | 0.58 | 0.06 |
| Multivariable HR (95% CI)§ | 1 (ref) | 0.64 (0.40 to 1.02) | 0.82 (0.51 to 1.33) | 1.07 (0.69 to 1.66) | 0.46 | 0.07 |
| Moderate/intense | ||||||
| No. cases (n=629) | 169 | 199 | 137 | 124 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.05 (0.85 to 1.29) | 0.92 (0.73 to 1.15) | 0.72 (0.57 to 0.91) | 0.002 | |
| Multivariable HR (95% CI)§ | 1 (ref) | 1.05 (0.85 to 1.30) | 0.94 (0.74 to 1.20) | 0.76 (0.59 to 0.98) | 0.02 | |
|
| ||||||
|
Dairy calcium intake (mg/day)
|
||||||
| <300 | 300–499 | 500–699 | ≥700 | |||
|
| ||||||
| Total colorectal cancer | ||||||
| Person-years(n=3,662,980) | 1,045,048 | 1,372,023 | 749,943 | 495,965 | ||
| No. cases (n=779) | 232 | 296 | 151 | 100 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.93 (0.78 to 1.11) | 0.86 (0.70 to 1.05) | 0.84 (0.66 to 1.06) | 0.08 | |
| Multivariable HR (95%CI) § | 1 (ref) | 0.94 (0.78 to 1.12) | 0.88 (0.71 to 1.09) | 0.89 (0.68 to 1.15) | 0.26 | |
|
| ||||||
| CASR | ||||||
| No/weak | ||||||
| No. cases (n=150) | 42 | 53 | 23 | 32 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.89 (0.59 to 1.34) | 0.70 (0.42 to 1.16) | 1.41 (0.88 to 2.24) | 0.27 | 0.04 |
| Multivariable HR (95% CI)§ | 1 (ref) | 0.89 (0.59 to 1.34) | 0.71 (0.42 to 1.19) | 1.50 (0.93 to 2.43) | 0.19 | 0.03 |
| Moderate/intense | ||||||
| No. cases (n=629) | 190 | 243 | 128 | 68 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.94 (0.78 to 1.14) | 0.89 (0.71 to 1.12) | 0.70 (0.53 to 0.93) | 0.01 | |
| Multivariable HR (95% CI)§ | 1 (ref) | 0.95 (0.78 to 1.15) | 0.92 (0.73 to 1.16) | 0.74 (0.55 to 1.00) | 0.06 | |
|
| ||||||
|
Calcium supplement (mg/day)
|
||||||
| <200 | 200–299 | 300–499 | ≥500 | |||
|
| ||||||
| Total colorectal cancer | ||||||
| Person-years(n=3,662,980) | 2,505,419 | 321,401 | 428,882 | 407,278 | ||
| No. cases (n=779) | 529 | 85 | 101 | 64 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.11 (0.88 to 1.41) | 1.01 (0.81 to 1.26) | 0.63 (0.48 to 0.82) | 0.006 | |
| Multivariable HR (95%CI)§ | 1 (ref) | 1.20 (0.94 to 1.52) | 1.14 (0.90 to 1.43) | 0.76 (0.58 to 1.01) | 0.31 | |
|
| ||||||
| CASR | ||||||
| No/weak | ||||||
| No. cases (n=150) | 100 | 14 | 22 | 14 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 0.87 (0.49 to 1.56) | 1.12 (0.69 to 1.82) | 0.70 (0.39 to 1.25) | 0.36 | 0.73 |
| Multivariable HR (95% CI)§ | 1 (ref) | 0.94 (0.52 to 1.68) | 1.27 (0.78 to 2.08) | 0.86 (0.48 to 1.54) | 0.89 | 0.71 |
| Moderate/intense | ||||||
| No. cases (n=629) | 429 | 71 | 79 | 50 | ||
| Age-adjusted HR (95% CI) | 1 (ref) | 1.17 (0.91 to 1.52) | 0.98 (0.76 to 1.25) | 0.61 (0.45 to 0.83) | 0.01 | |
| Multivariable HR (95% CI)§ | 1 (ref) | 1.27 (0.98 to 1.65) | 1.10 (0.86 to 1.42) | 0.74 (0.54 to 1.01) | 0.28 | |
CI, confidence interval; HR, hazard ratio.
Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute HRs and 95% CIs.
All analyses were stratified by age (in month), year of questionnaire return and sex, as well as restricted to cases with CASR data.
Linear trend test using the median intake of each category.
The likelihood ratio test was used to test for the heterogeneity of the association between calcium intake and colorectal cancer risk by expression of CASR.
Multivariable hazard ratios were adjusted for age (in month), race (Caucasian vs. non-Caucasian), adult BMI (< 25, 25 – < 27.5, 27.5 – < 30, or ≥ 30 kg/m2), smoking (0, 1–10, or > 10 pack-years), history of colorectal cancer in a parent or sibling (yes or no), history of sigmoidoscopy/colonoscopy (yes or no), physical activity (< 3, 3 – < 27, ≥ 27 MET-hours/week), regular aspirin use (yes, no), alcohol consumption (0 – < 5, 5 – < 15, or ≥ 15 g/day), total intake of vitamin D, folate, red meat and processed meat (all in tertiles).