Appendix 1 (as supplied by the authors): Supplementary Material 1: Methods for Population Attributable Cancer Risks for Excess Salt and Insufficient Calcium and Vitamin D To estimate the population attributable cancer risk associated with excess salt and insufficient calcium and vitamin D intake in Alberta, similar methods to those used by Parkin for analyses related to salt consumption (1) were used and are described below. The relative risks (RRs) used in these analyses are summarized in Table 1 and the prevalence of each of these exposures was estimated from data obtained from Alberta s Tomorrow Project. Prevalence of Exposure Data on salt, calcium and vitamin D consumption were available from Alberta s Tomorrow Project cohort (2). The Tomorrow Project cohort is a geographically-based cohort study conducted in Alberta, Canada that included a diet history questionnaire as part of baseline data collection. The main population attributable risk analyses used Alberta s Tomorrow Project cohort data collected between 2000 and 2009. Data from Alberta s Tomorrow Project diet history questionnaire were used to estimate total and mean sodium intake in milligrams per day, dietary calcium intake in milligrams per day and vitamin D intake from diet and supplements combined in International Units (IU) per day (Table 2). While serum vitamin D measures are the most representative in terms of characterizing all potential sources of vitamin D (sun exposure, diet, supplements), no Alberta-specific data on serum measures of vitamin D were available. Although serum vitamin D levels are available on a national level from the Canadian Health Measures Survey, the large geographic variation across Canada and influence of latitude on vitamin D measures (3) means that serum vitamin D measures from a national sample are unlikely to be fully representative of similar measures focused on Alberta. As such, data from Alberta s Tomorrow Project were used to estimate population attributable risks associated with dietary and supplemental vitamin D intake as these
are likely to produce the most accurate estimates for Alberta, understanding that true vitamin D levels may be underestimated in the absence of serum measures. Statistical Analyses - Salt To estimate population attributable risks for salt consumption, mean sodium (Na) values were first converted to grams of salt per day according to equation 1 (4): ( ) 1: ( ) = 2.5 1000 Based on an excess risk of 0.08 per gram of salt per day, the relative risk of stomach cancer associated with x grams of salt intake was estimated using equation 2: 2: = exp(0.08 ) exp(0.08 5.75) where represents the mean salt intake in grams per day and 5.75 represents the level of salt intake in grams per day recommended in public health guidelines produced by Health Canada. The excess number of stomach cancer cases attributable to salt consumption was then estimated by subtracting (# observed # expected), where the number of expected cases in each age-sex group were estimated as: 3: # = # The number of observed stomach cancer cases was obtained from cancer incidence data from the Alberta Cancer Registry for 2012. Population attributable risks were then estimated by expressing the number of excess cases as a proportion of the total number observed in each age group. Statistical Analyses Calcium and Vitamin D To estimate population attributable risks for both insufficient dietary calcium and vitamin D consumption, methods similar to those for salt were employed. For adults over 19 years of age,
the recommended dietary allowance per day by Health Canada for calcium consumption is 1000 1200 mg (5) and as such, the midpoint of this range (1100 mg/day) was used as the cutoff for this analysis. Similarly, as the Health Canada recommendation for intake of vitamin D is 600 IU per day for the majority of the population (5), this cutoff was used for our analyses. We used the inverse of the formula for salt consumption (1) to estimate relative risk at a specific level of intake for both dietary calcium and vitamin D, as shown in Equations 4 and 5, respectively: 4: = exp( 200 ) exp( 200 200 ) 5: = exp( 100 100 ) exp( 100 100 ) As for salt consumption, the excess number of cases for both insufficient dietary calcium and vitamin D consumption was estimated by subtracting (# observed # expected), where the number of expected cases in each age-sex group was estimated as shown in Equation 3. The observed number of colorectal and breast cancer cases for these analyses was obtained from cancer incidence data from the Alberta Cancer Registry for 2012. As with salt, the population attributable risks were estimated by expressing the number of excess cases as a proportion of the observed cases for each cancer site. REFERENCES 1. Parkin DM. 7. Cancers attributable to dietary factors in the UK in 2010. IV. Salt. Br J Cancer 2011;S31-3. 2. Bryant H, Robson PJ, Ullman R, Friedenreich CM, Dawe U. Population-based cohort development in Alberta, Canada: a feasiblity study. Chronic Dis Can 2006;27(2):51 9. 3. Holick MF. Environmental factors that influence the cutaneous production of vitamin D.
Am J Clin Nutr 1995;61(3 Suppl):638S 645S. 4. Institute of Medicine. Dietary Reference Intakes: Water, Potassium, Sodium, Chloride, and Sulfate. Washingtion, DC: Institute of Medicine, 2004. 5. Canada H. Vitamin D and Calcium: Updated Dietery Reference Intakes 2012 [Internet]. Available from: http://www.hc-sc.gc.ca/fn-an/nutrition/vitamin/vita-d-eng.php
Table 1 Relative risks linking dietary calcium intake with colorectal, colon and rectal cancer Cancer Exposure Units Gender Risk Estimate Source Site Excess Risk Salt Stomach gram/day All 1.08 WCRF, 2007 0.08 Dietary Calcium Colorectal 200mg/day All 0.94 WCRF, 2011 0.06 Colon 200mg/day All 0.93 WCRF, 2011 0.07 Rectal 200mg/day All 0.94 WCRF, 2011 0.06 Vitamin D Breast 100 IU/day Women 0.99 Kim& Je, 2014 0.01 Colon 100 IU/day All 0.95 WCRF, 2011 0.05 Colorectal 100 IU/day All 1.00 WCRF, 2011 0 Rectal 100 IU/day All 0.96 WCRF, 2011 0.04
Table 2 Mean levels of sodium, calcium and vitamin D consumption from Alberta Tomorrow Project data Sodium/Salt Consumption Gender Age Group Mean Sodium Consumption - mg/day (Standard Error) Mean Salt Consumption - g/day (Standard Error) Alberta s Tomorrow Project Men 35 44 3740.11 (30.14) 9.35 (0.08) Men 45 54 3479.32 (26.20) 8.70 (0.06) Men 55 64 3180.38 (27.78) 7.95 (0.07) Men 65 3038.07 (43.76) 7.60 (0.11) Men All 3438.22 (15.46) 8.60 (0.04) Women 35 44 2723.77 (15.91) 6.81 (0.04) Women 45 54 2574.79 (13.98) 6.44 (0.04) Women 55 64 2480.76 (16.31) 6.20 (0.04) Women 65 2347.76 (24.35) 5.87 (0.06) Women All 2574.62 (8.38) 6.44 (0.02) Dietary Calcium Consumption Gender Age Group Mean Dietary Calcium Intake mg/day Standard Error Alberta s Tomorrow Project Men 35 44 1102.06 11.4 Men 45 54 966.71 8.9 Men 55 64 864.37 9.7 Men 65 828.45 15.2 Men All 967.32 5.5 Women 35 44 879.40 6.8 Women 45 54 824.46 5.6 Women 55 64 786.55 6.7
Women 65 751.41 9.9 Women All 824.45 3.5 Vitamin D (Diet and Supplements) Gender Age Group Mean Vitamin D Intake IU/day Standard Error Men 35 44 259 4.6 Men 45 54 340 3.9 Men 55 64 366 4.9 Men 65 397 8.7 Men All 358 2.5 Women 35 44 346 3.3 Women 45 54 372 3.3 Women 55 64 437 4.2 Women 65 458 6.9 Women All 388 2.0