There were 228 renal cell cancer cases diagnosed among 27,111 men with dietary information available, comprising 93% of the entire cohort of 29,133 participants. The mean and median follow-up times among the 27,111 men were both equal to 15.2 years. The response rate to enrollment in the primary intervention study was 79.3% (42,947/54,171) among smokers in the target population of southern Finland, among whom 67.8% (29,133/42,947) met the inclusion criteria. Drop-out rates (including from deaths) within the randomized groups did not differ significantly at the end of the intervention period (30.1%–31.3% range) (data not shown).
Vitamin D intake values were correlated with total fish (r
0.45), Baltic herring (r
0.28), rainbow trout (r
= 0.22), margarine (r
0.22), and egg dishes (r
0.12) (data not shown). Flavonoid intake values were correlated with tea (r
0.93), apples and pears (r
0.29), and berries (r
= 0.21), with lower correlations for peanuts (r
0.07) and wine (r
= 0.08). All correlations were statistically significant (P
There was no effect of the alpha-tocopherol or beta-carotene intervention on the incidence of renal cell cancer, and serum levels of alpha-tocopherol and beta-carotene were not associated with risk (data not shown). Body mass index, pack-years of smoking, systolic blood pressure, alcohol intake, leisure time physical activity, urban residence, and dietary intake of quercetin, vitamin D (dietary and total), and Baltic herring were significantly associated with renal cell cancer risk in models adjusting for age and randomization group (). There was no statistically significant association with total flavonoids, other flavonoids, other vitamin D-containing foods, total fish intake, or other types of fish (rainbow trout, frozen, fresh, and salted/canned). Ptrend
values were statistically significant for body mass index, systolic blood pressure, alcohol intake, and intakes of quercetin, vitamin D (dietary and total), and Baltic herring. In addition to the statistically significant variables above, variables with Ptrend
0.15 that were included in the stepwise selection and backward variable elimination models included catechin, total calcium, frozen fish, and liver dishes.
Hazard Ratio of Renal Cell Cancer Adjusted for Age and Randomization Group, Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, 1985–2002
In stepwise selection and backward variable elimination models, statistically significant variables (P
0.05) included body mass index, systolic blood pressure, physical activity, and intakes of alcohol, quercetin, and Baltic herring.
In the final model (), there was a 40% decreased risk among individuals consuming the highest amounts of quercetin (for individuals consuming >9.1 mg/day compared with individuals consuming ≤4.8 mg/day: hazard ratio (HR)
0.6, 95% confidence interval (CI): 0.4, 0.9), and the trend was statistically significant (Ptrend
0.015). These results were similar among individuals above (>26 kg/m2
) and below (<26 kg/m2
) the median body mass index (Pinteraction
0.613), although the trend was statistically significant only among those with values above the median body mass index (Ptrend
Final Model of the Hazard Ratioa of Renal Cell Cancer in Relation to Flavonoid and Fish Intake Stratified by Body Mass Index, Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, 1985–2002
Conversely, there was a 2-fold increased risk of renal cell cancer among individuals consuming, on average, 12.2 g or more per day of Baltic herring (HR
2.0, 95% CI: 1.4, 3.0), compared with individuals consuming 2.1 g or less, and the trend was statistically significant (Ptrend
0.001). Among individuals whose body mass index was below the median (<26 kg/m2
), intakes at the third and fourth quartiles were associated with a 2.0- and a 2.7-fold elevated risk (Ptrend
0.001), whereas the same intake levels among individuals whose body mass index was above the median (>26 kg/m2
) were associated with a 1.7- and a 1.6-fold elevated risk, respectively (Ptrend
0.090). The interaction was not statistically significant (Pinteraction
In other models classifying those individuals with both lowest body mass index (≤23.7 kg/m2) and lowest herring intake (≤2.1 g/day) as the reference group, the risk for renal cell cancer ranged from 2.3- to 4.3-fold higher among individuals with both higher body mass index (quartiles 2–4) and highest Baltic herring intake (>12.2 g/day) (). (Statistically significant hazard ratios are indicated by solid shapes in the figure.)
Figure 1. Hazard ratio of renal cell cancer in relation to Baltic herring intake and body mass index, Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, 1985–2002. The reference group was body mass index of ≤23.7 kg/m2 and Baltic herring intake (more ...)
There was no association between vitamin D intake (total or dietary) and renal cell cancer with adjustment for the effects of the other variables in the final model (for the highest vs. the lowest quartile of total vitamin D intake: HR
1.0, 95% CI: 0.7, 1.4) (data not shown).
Geographically stratified models of renal cell cancer and fish intake
There were no statistically significant interactions between place of residence (urban, coastal, or combinations thereof) and fish intake (data not shown), but there was a suggestion of increased risk with higher consumption of Baltic herring, rainbow trout, and total fish intake, especially in the urban Baltic coast ().
Hazard Ratioa of Renal Cell Cancer in Relation to Fish Intake Stratified by Geographic Location, Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, 1985–2002