Introduction
Methods
Study | Country |
n
| Mean | % | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Controls | Cases | Age at diagnosis (years) | PSA at diagnosis (ng/ml) | Screen detectedb (%) | Family history prostate cancer | Gleason score 8–10 | Advanced stage (T3 or T4) | Distant spread (SEER) | ||
CPCS1 | Denmark | 2,771 | 848 | 69.5 | 48.0 | 0.0 | 8.2 | 35.0 | – | – |
CPCS2 | Denmark | 1,009 | 265 | 64.9 | 36.0 | 0.0 | 14.7 | 10.6 | – | – |
EPIC | Europea
| 1,079 | 722 | 64.9 | 19.7 | 0.0 | – | 3.6 | 3.8 | 0.9 |
ESTHER | Germany | 318 | 313 | 65.5 | 58.7 | 61.9 | 8.9 | 9.1 | 26.4 | 3.4 |
FHCRC | USA | 730 | 761 | 59.7 | 16.1 | – | 21.7 | 10.4 | – | 2.6 |
IPO-Porto | Portugal | 66 | 183 | 59.3 | 8.3 | 82.8 | 20.0 | 15.8 | 64.5 | 0.0 |
MAYO | USA | 488 | 767 | 65.2 | 15.5 | 73.7 | 29.1 | 33.0 | 44.4 | 0.5 |
MCCS | Australia | 1,169 | 1,698 | 58.5 | 136.6 | – | 23.4 | 11.0 | 14.0 | 0.8 |
MEC | USA | 829 | 819 | 69.5 | – | – | 13.0 | 36.0 | – | 2.8 |
MOFFITT | USA | 100 | 412 | 64.9 | 7.3 | 0.0 | 22.9 | 11.2 | 3.5 | 0.5 |
PCMUS | Bulgaria | 140 | 151 | 69.3 | 32.5 | 21.2 | 5.3 | 29.8 | 42.4 | 18.5 |
PPF-UNIS | UK | 176 | 244 | 68.9 | 32.0 | – | 25.3 | 10.9 | 25.7 | 9.0 |
Poland | Poland | 359 | 438 | 67.7 | 40.2 | 0.0 | 10.6 | 14.0 | 36.8 | 2.8 |
ProMPT | UK | 1 | 166 | 66.3 | 33.0 | 0.0 | 34.6 | 18.9 | 32.7 | 7.8 |
ProtecT | UK | 1,474 | 1,542 | 62.8 | 9.6 | 100.0 | 7.9 | 5.7 | 11.3 | 0.4 |
QLD/ProsCan | Australia | 87 | 186 | 61.3 | 6.7 | – | 36.2 | 4.0 | 0.0 | 0.0 |
STHMI | Sweden | 2,224 | 2,002 | 66.2 | – | – | 20.2 | 10.2 | 14.2 | 1.6 |
TAMPERE | Finland | 2,413 | 2,753 | 68.2 | 69.1 | 46.8 | – | 15.4 | 21.0 | 7.3 |
UKGPCS | UK | 4,182 | 4,549 | 63.8 | 83.9 | 28.9 | 23.4 | 17.2 | 32.9 | 10.7 |
ULM | Germany | 354 | 601 | 63.8 | 19.1 | – | 44.9 | 15.5 | 39.9 | 1.1 |
UTAH | USA | 245 | 440 | 62.6 | – | – | 51.4 | 16.1 | – | 4.7 |
WUGS | USA | 0 | 988 | 60.8 | 6.2 | – | 42.3 | 7.9 | 24.2 | 0.1 |
Genotyping
Constructing genetic risk scores for BMI and height
Statistical analysis
Sensitivity analyses
Results
Associations of genetic risk scores with measured height and BMI in ProtecT
n
| Mean difference | 95 % CI |
r
2 (%) |
F-statistic | ||
---|---|---|---|---|---|---|
Lower limit | Upper limit | |||||
Height | 907 | 0.26 | 0.20 | 0.33 | 6.31 | 67.6 |
BMI | 901 | 0.12 | 0.06 | 0.19 | 1.46 | 13.6 |
Associations of genetic risk scores with potential confounders in ProtecT
n
| Observed phenotypea
| Genetic risk scoresa
| |||||||
---|---|---|---|---|---|---|---|---|---|
Effect estimate | Confidence intervalb
|
p value | Effect estimate | Confidence intervalb
|
p value | ||||
Lower | Upper | Lower | Upper | ||||||
Standardized height | Odds ratioc
| Odds ratioc
| |||||||
Binary variables | |||||||||
Diabetes | 726 | 0.91 | 0.64 | 1.30 | 0.62 | 0.94 | 0.70 | 1.25 | 0.66 |
Managerial occupation | 818 | 1.21 | 1.06 | 1.40 | 0.006 | 0.91 | 0.79 | 1.04 | 0.17 |
Strenuous exercise | 621 | 1.13 | 0.96 | 1.33 | 0.13 | 1.03 | 0.87 | 1.21 | 0.75 |
Moderate or strenuous exercise | 621 | 1.15 | 0.96 | 1.37 | 0.12 | 1.01 | 0.85 | 1.20 | 0.90 |
≥3 drinks in the last week | 820 | 1.13 | 0.98 | 1.30 | 0.09 | 1.05 | 0.91 | 1.22 | 0.47 |
Passive smoker | 752 | 1.03 | 0.89 | 1.19 | 0.72 | 1.00 | 0.86 | 1.16 | 0.99 |
Ever smoker | 780 | 1.10 | 0.95 | 1.27 | 0.21 | 1.08 | 0.93 | 1.25 | 0.33 |
Current smoker | 552 | 1.09 | 0.89 | 1.35 | 0.40 | 1.21 | 0.97 | 1.51 | 0.08 |
Benign hypertrophy of the prostate | 704 | 0.77 | 0.58 | 1.02 | 0.07 | 1.38 | 1.01 | 1.88 | 0.05 |
Regression coefficientc
| Regression coefficientc
| ||||||||
---|---|---|---|---|---|---|---|---|---|
Continuous variables | |||||||||
PSA (ng/ml) | 828 | −1.15 | −2.01 | −0.29 | 0.009 | −0.31 | −1.32 | 0.70 | 0.55 |
IGF-I (ng/ml) | 718 | 1.80 | −2.23 | 5.83 | 0.38 | −2.53 | −6.31 | 1.25 | 0.19 |
Age (years) | 1,109 | −0.53 | −0.83 | −0.24 | <0.001 | 0.07 | −0.23 | 0.38 | 0.64 |
Standardized BMI | Odds ratioc
| Odds ratioc
| |||||||
---|---|---|---|---|---|---|---|---|---|
Binary variables | |||||||||
Diabetes | 724 | 1.90 | 1.45 | 2.48 | <0.001 | 1.16 | 0.86 | 1.57 | 0.33 |
Managerial occupation | 813 | 0.96 | 0.83 | 1.10 | 0.54 | 0.91 | 0.79 | 1.05 | 0.20 |
Strenuous exercise | 617 | 0.91 | 0.77 | 1.08 | 0.28 | 1.05 | 0.89 | 1.23 | 0.57 |
Moderate or strenuous exercise | 617 | 0.80 | 0.66 | 0.96 | 0.02 | 1.01 | 0.85 | 1.20 | 0.94 |
≥3 drinks in the last week | 814 | 0.87 | 0.75 | 1.01 | 0.07 | 0.90 | 0.78 | 1.04 | 0.17 |
Passive smoker | 748 | 1.12 | 0.97 | 1.30 | 0.13 | 0.97 | 0.84 | 1.12 | 0.65 |
Ever smoker | 776 | 1.09 | 0.93 | 1.27 | 0.29 | 1.09 | 0.94 | 1.27 | 0.25 |
Current smoker | 548 | 0.71 | 0.54 | 0.94 | 0.02 | 1.18 | 0.95 | 1.48 | 0.13 |
Benign hypertrophy of the prostate | 700 | 0.92 | 0.69 | 1.23 | 0.56 | 0.94 | 0.71 | 1.25 | 0.66 |
Regression coefficientc
| Regression coefficientc
| ||||||||
---|---|---|---|---|---|---|---|---|---|
Continuous variables | |||||||||
PSA (ng/ml) | 822 | −0.25 | −1.55 | 1.05 | 0.70 | −0.21 | −0.96 | 0.54 | 0.58 |
IGF-I (ng/ml) | 714 | −5.38 | −9.12 | −1.64 | 0.005 | 1.77 | −1.97 | 5.51 | 0.35 |
Age (years) | 1,101 | −0.28 | −0.60 | 0.04 | 0.08 | −0.04 | −0.33 | 0.25 | 0.79 |
Association of the genetic risk scores and prostate cancer risk and mortality
n
| Unadjusted | Adjusteda
| ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Odds ratio
c
| Confidence intervalb
|
p value | Odds ratio
c
| Confidence intervalb
|
p value |
p heterogeneity
d
| ||||
Lower | Upper | Lower | Upper | |||||||
Height
| ||||||||||
Controls | 20,214 | 1.00 | – | – | – | 1.00 | – | – | – | – |
All prostate cancers | 20,848 | 0.96 | 0.91 | 1.01 | 0.12 | 0.99 | 0.97 | 1.01 | 0.23 | |
Localized prostate cancer | 12,975 | 0.96 | 0.88 | 1.03 | 0.27 | 1.00 | 0.98 | 1.02 | 0.72 | 0.05 |
Advanced prostate cancer | 4,325 | 0.90 | 0.83 | 0.98 | 0.02 | 0.96 | 0.93 | 0.99 | 0.01 | |
Low-grade prostate cancer | 8,784 | 0.96 | 0.90 | 1.02 | 0.20 | 0.99 | 0.96 | 1.01 | 0.30 | 0.55 |
High-grade prostate cancer | 8,230 | 0.97 | 0.92 | 1.02 | 0.26 | 1.00 | 0.98 | 1.02 | 0.85 | |
BMI
| ||||||||||
Controls | 20,214 | 1.00 | – | – | – | 1.00 | – | – | – | – |
All prostate cancers | 20,848 | 0.98 | 0.96 | 1.01 | 0.15 | 0.98 | 0.96 | 1.00 | 0.07 | |
Localized prostate cancer | 12,975 | 0.98 | 0.96 | 1.00 | 0.10 | 0.98 | 0.96 | 1.00 | 0.05 | 0.64 |
Advanced prostate cancer | 4,325 | 1.01 | 0.97 | 1.05 | 0.69 | 1.01 | 0.97 | 1.05 | 0.62 | |
Low-grade prostate cancer | 8,784 | 0.98 | 0.94 | 1.02 | 0.25 | 0.97 | 0.94 | 1.00 | 0.09 | 0.13 |
High-grade prostate cancer | 8,230 | 1.00 | 0.97 | 1.02 | 0.69 | 1.00 | 0.98 | 1.01 | 0.65 |
Number of participants | Number of failures | Years at risk (1000s) | Unadjusted | Adjusteda
| ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Hazard ratio
c
| Confidence interval
b
|
p value | Hazard ratio
c
| Confidence interval
b
|
p value |
p heterogeneity
d
| ||||||
Lower | Upper | Lower | Upper | |||||||||
All-cause mortality
| ||||||||||||
Height | ||||||||||||
All cases | 14,649 | 3,591 | 105 | 1.02 | 0.97 | 1.08 | 0.47 | 1.00 | 0.96 | 1.04 | 0.88 | |
Localized | 8,553 | 1,447 | 65 | 1.01 | 0.93 | 1.09 | 0.81 | 1.00 | 0.93 | 1.07 | 0.97 | 0.20 |
Advanced | 3,435 | 1,332 | 25 | 1.08 | 0.98 | 1.18 | 0.11 | 1.07 | 0.99 | 1.14 | 0.07 | |
Low grade | 5,684 | 905 | 43 | 1.04 | 0.97 | 1.11 | 0.32 | 1.02 | 0.95 | 1.09 | 0.57 | 0.80 |
High grade | 5,892 | 1,365 | 36 | 1.02 | 0.97 | 1.08 | 0.36 | 1.01 | 0.96 | 1.06 | 0.71 | |
BMI | ||||||||||||
All cases | 14,649 | 3,591 | 105 | 1.02 | 0.99 | 1.05 | 0.18 | 1.02 | 0.99 | 1.05 | 0.23 | |
Localized | 8,553 | 1,447 | 65 | 1.04 | 0.99 | 1.10 | 0.09 | 1.04 | 0.99 | 1.10 | 0.09 | 0.28 |
Advanced | 3,435 | 1,332 | 25 | 1.01 | 0.98 | 1.04 | 0.50 | 1.01 | 0.98 | 1.05 | 0.59 | |
Low grade | 5,684 | 905 | 43 | 1.09 | 1.04 | 1.15 | 0.001 | 1.08 | 1.03 | 1.14 | 0.002 | 0.03 |
High grade | 5,892 | 1,365 | 36 | 1.00 | 0.96 | 1.05 | 0.89 | 1.00 | 0.95 | 1.05 | 0.98 | |
Prostate cancer-specific mortality
| ||||||||||||
Height | ||||||||||||
All cases | 14,649 | 1,483 | 105 | 1.02 | 0.98 | 1.06 | 0.44 | 1.00 | 0.97 | 1.04 | 0.87 | |
Localized | 8,553 | 363 | 65 | 0.98 | 0.91 | 1.07 | 0.72 | 0.99 | 0.91 | 1.08 | 0.79 | 0.29 |
Advanced | 3,435 | 745 | 25 | 1.05 | 1.00 | 1.10 | 0.06 | 1.04 | 1.00 | 1.09 | 0.07 | |
Low grade | 5,684 | 188 | 43 | 1.13 | 1.06 | 1.21 | <0.001 | 1.13 | 1.08 | 1.20 | <0.001 | <0.001 |
High grade | 5,892 | 678 | 36 | 0.97 | 0.93 | 1.02 | 0.20 | 0.97 | 0.93 | 1.01 | 0.19 | |
BMI | ||||||||||||
All cases | 14,649 | 1,483 | 105 | 0.99 | 0.96 | 1.03 | 0.76 | 1.00 | 0.96 | 1.04 | 0.94 | |
Localized | 8,553 | 363 | 65 | 0.95 | 0.88 | 1.03 | 0.22 | 0.95 | 0.87 | 1.05 | 0.31 | 0.09 |
Advanced | 3,435 | 745 | 25 | 1.04 | 0.98 | 1.10 | 0.18 | 1.05 | 0.99 | 1.10 | 0.11 | |
Low grade | 5,684 | 188 | 43 | 0.95 | 0.89 | 1.01 | 0.08 | 0.95 | 0.88 | 1.01 | 0.12 | 0.03 |
High grade | 5,892 | 678 | 36 | 1.05 | 0.99 | 1.11 | 0.12 | 1.05 | 0.98 | 1.13 | 0.14 |