Table 3.
Association between quintiles of plasma α-tocopherol and prostate cancer risk stratified by Gleason grade, smoking status, follow-up time, and by trial supplementation, SELECT case-cohort study
| Plasma α-tocopherol quintiles | Ptrend | |||||
|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | ||
| Histologic grade | ||||||
| Gleason 2–6 | ||||||
| Cases/sub-cohort, na | 171/681 | 201/656 | 209/629 | 209/616 | 203/624 | |
| Overall HRb (95% CI) | 1.00 | 1.14 (0.89–1.45) | 1.13 (0.88–1.44) | 1.12 (0.88–1.44) | 1.06 (0.82–1.36) | 0.80 |
| Placebo | 1.00 | 1.04 (0.64–1.69) | 1.16 (0.71–1.89) | 0.94 (0.57–1.53) | 1.04 (0.63–1.73) | 0.93 |
| α-Tocopherol only | 1.00 | 0.83 (0.52–1.32) | 0.95 (0.60–1.52) | 0.82 (0.51–1.32) | 0.56 (0.34–0.93) | 0.04 |
| Selenomethionine only | 1.00 | 1.12 (0.69–1.81) | 1.33 (0.82–2.16) | 1.22 (0.75–1.99) | 1.10 (0.67–1.79) | 0.65 |
| α-Tocopherol and selenomethionine | 1.00 | 1.72 (1.04–2.85) | 0.94 (0.56–1.58) | 1.62 (0.98–2.68) | 1.75 (1.06–2.91) | 0.08 |
| Any selenomethionine | 1.00 | 1.37 (0.96–1.94) | 1.15 (0.81–1.63) | 1.41 (0.99–2.00) | 1.39 (0.98–1.98) | 0.10 |
| Any α-tocopherol | 1.00 | 1.17 (0.83–1.64) | 0.96 (0.68–1.35) | 1.12 (0.80–1.59) | 0.98 (0.69–1.40) | 0.82 |
| Gleason 7–10 | ||||||
| Cases/sub-cohort, na | 72/681 | 89/656 | 103/629 | 117/616 | 117/624 | |
| Overall HRb (95% CI) | 1.00 | 1.15 (0.81–1.64) | 1.45 (1.03–2.04) | 1.58 (1.13–2.21) | 1.59 (1.13–2.24) | 0.001 |
| Placebo | 1.00 | 1.64 (0.75–3.60) | 2.50 (1.18–5.30) | 1.81 (0.85–3.86) | 1.73 (0.78–3.82) | 0.28 |
| α-Tocopherol only | 1.00 | 0.89 (0.47–1.69) | 0.89 (0.47–1.68) | 1.24 (0.67–2.32) | 0.93 (0.48–1.80) | 0.77 |
| Selenomethionine only | 1.00 | 1.13 (0.52–2.45) | 2.10 (1.01–4.36) | 2.41 (1.19–4.88) | 2.58 (1.27–5.26) | 0.001 |
| α-Tocopherol and selenomethionine | 1.00 | 1.27 (0.65–2.50) | 1.24 (0.64–2.41) | 1.51 (0.78–2.92) | 1.75 (0.92–3.32) | 0.08 |
| Any selenomethionine | 1.00 | 1.21 (0.73–2.01) | 1.62 (1.00–2.64) | 1.92 (1.18–3.10) | 2.12 (1.32–3.40) | 0.0002 |
| Any α-tocopherol | 1.00 | 1.08 (0.68–1.71) | 1.06 (0.67–1.68) | 1.35 (0.86–2.13) | 1.29 (0.81–2.04) | 0.17 |
| Smoking status | ||||||
| Never smokers | ||||||
| Cases/sub-cohort, na | 146/289 | 163/276 | 168/268 | 172/264 | 177/259 | |
| Overall HRb (95% CI) | 1.00 | 0.96 (0.72–1.30) | 1.05 (0.78–1.41) | 1.03 (0.76–1.40) | 1.10 (0.81–1.49) | 0.44 |
| Placebo | 1.00 | 1.00 (0.54–1.85) | 1.21 (0.65–2.24) | 0.81 (0.42–1.57) | 0.99 (0.51–1.92) | 0.78 |
| α-Tocopherol only | 1.00 | 0.66 (0.37–1.19) | 0.66 (0.37–1.19) | 0.67 (0.37–1.21) | 0.58 (0.32–1.05) | 0.11 |
| Selenomethionine only | 1.00 | 1.29 (0.71–2.35) | 1.64 (0.90–2.97) | 1.47 (0.80–2.69) | 1.84 (1.00–3.39) | 0.05 |
| α-Tocopherol and selenomethionine | 1.00 | 1.19 (0.65–2.18) | 0.89 (0.49–1.63) | 1.08 (0.58–2.01) | 1.66 (0.90–3.06) | 0.18 |
| Any selenomethionine | 1.00 | 1.19 (0.78–1.82) | 1.16 (0.76–1.77) | 1.35 (0.88–2.08) | 1.70 (1.11–2.61) | 0.01 |
| Any α-tocopherol | 1.00 | 0.90 (0.59–1.36) | 0.79 (0.52–1.20) | 0.84 (0.55–1.29) | 0.91 (0.59–1.39) | 0.62 |
| Current & former smokers | ||||||
| Cases/sub-cohort, na | 146/402 | 187/369 | 193/363 | 202/352 | 186/364 | |
| Overall HRb (95% CI) | 1.00 | 1.40 (1.06–1.84) | 1.35 (1.03–1.78) | 1.43 (1.09–1.88) | 1.26 (0.95–1.67) | 0.18 |
| Placebo | 1.00 | 1.18 (0.67–2.10) | 1.18 (0.67–2.06) | 1.14 (0.65–1.99) | 1.01 (0.57–1.80) | 0.93 |
| α-Tocopherol only | 1.00 | 1.05 (0.62–1.77) | 1.27 (0.75–2.16) | 0.99 (0.58–1.67) | 0.85 (0.48–1.50) | 0.51 |
| Selenomethionine only | 1.00 | 1.17 (0.63–2.16) | 1.48 (0.82–2.66) | 1.64 (0.91–2.93) | 1.52 (0.84–2.75) | 0.09 |
| α-Tocopherol and selenomethionine | 1.00 | 1.68 (0.98–2.89) | 1.11 (0.64–1.92) | 1.86 (1.09–3.16) | 1.53 (0.88–2.64) | 0.15 |
| Any selenomethionine | 1.00 | 1.33 (0.87–2.03) | 1.47 (0.98–2.21) | 1.60 (1.06–2.41) | 1.44 (0.95–2.20) | 0.06 |
| Any α-tocopherol | 1.00 | 1.33 (0.92–1.93) | 1.16 (0.80–1.70) | 1.32 (0.90–1.92) | 1.11 (0.75–1.63) | 0.72 |
| Follow-up time to diagnosis | ||||||
| < 3 years | ||||||
| Cases/sub-cohort, na | 113/681 | 124/656 | 158/629 | 149/616 | 154/624 | |
| Overall HRb (95% CI) | 1.00 | 1.08 (0.80–1.45) | 1.41 (1.06–1.87) | 1.29 (0.97–1.72) | 1.30 (0.98–1.74) | 0.03 |
| Placebo | 1.00 | 0.96 (0.55–1.69) | 1.27 (0.74–2.19) | 0.74 (0.41–1.34) | 0.88 (0.48–1.59) | 0.42 |
| α-Tocopherol only | 1.00 | 0.89 (0.51–1.55) | 1.05 (0.61–1.80) | 1.22 (0.71–2.08) | 0.73 (0.41–1.27) | 0.61 |
| Selenomethionine only | 1.00 | 1.14 (0.59–2.19) | 2.40 (1.31–4.37) | 1.94 (1.06–3.54) | 2.09 (1.15–3.79) | 0.003 |
| α-Tocopherol and selenomethionine | 1.00 | 1.31 (0.73–2.36) | 1.24 (0.69–2.25) | 1.67 (0.93–2.99) | 2.04 (1.16–3.61) | 0.01 |
| Any selenomethionine | 1.00 | 1.27 (0.82–1.96) | 1.78 (1.17–2.70) | 1.78 (1.17–2.71) | 2.08 (1.38–3.12) | 0.0001 |
| Any α-tocopherol | 1.00 | 1.09 (0.73–1.64) | 1.14 (0.76–1.70) | 1.39 (0.93–2.06) | 1.22 (0.81–1.83) | 0.17 |
| ≥ 3 years | ||||||
| Cases/sub-cohort, na | 186/631 | 219/614 | 203/594 | 226/575 | 208/577 | |
| Overall HRb (95% CI) | 1.00 | 1.10 (0.87–1.40) | 1.00 (0.79–1.28) | 1.08 (0.85–1.38) | 1.01 (0.78–1.29) | 0.94 |
| Placebo | 1.00 | 1.18 (0.70–1.98) | 1.33 (0.79–2.25) | 1.15 (0.69–1.91) | 1.04 (0.60–1.81) | 0.99 |
| α-Tocopherol only | 1.00 | 0.78 (0.49–1.23) | 0.79 (0.49–1.26) | 0.68 (0.42–1.10) | 0.58 (0.35–0.96) | 0.03 |
| Selenomethionine only | 1.00 | 1.05 (0.65–1.70) | 1.00 (0.61–1.65) | 1.29 (0.80–2.09) | 1.14 (0.69–1.86) | 0.40 |
| α-Tocopherol and selenomethionine | 1.00 | 1.56 (0.95–2.55) | 0.94 (0.57–1.53) | 1.37 (0.84–2.25) | 1.36 (0.82–2.24) | 0.44 |
| Any selenomethionine | 1.00 | 1.27 (0.90–1.79) | 0.99 (0.70–1.40) | 1.33 (0.94–1.88) | 1.28 (0.90–1.82) | 0.19 |
| Any α-tocopherol | 1.00 | 1.09 (0.78–1.52) | 0.87(0.62–1.21) | 0.95 (0.67–1.35) | 0.90 (0.63–1.27) | 0.36 |
a
The sub-cohort contains both cases and non-cases, with overlap between case and sub-cohort numbers.
b
Hazard ratios (HR) and 95% confidence intervals (CI) based on proportional hazard regression, mutually adjusted for γ-tocopherol or α-tocopherol (continuous), with PSA, family history of prostate cancer, BMI, diabetes, cholesterol, and smoking status included in the models. Results are also age- and race-adjusted as a result of all models being stratified by age/race groups before being weighted and combined to generate summary statistics. The first plasma tocopherol quintiles serve as Referent categories. Interaction P-values for plasma α-tocopherol x smoking status are 0.95, 0.75, and 0.94 for the four intervention arm, any selenium, and any vitamin E strata (respectively). Interaction P-values for plasma α-tocopherol x follow-up time to diagnosis are 0.21, 0.35, and 0.30 for the four intervention arm, any selenium, and any vitamin E strata (respectively).