전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

- i -

- ii -

- iii -

- iv -

- v -

- vi -

- vii -

- viii -

- ix -

- x -

- 1 -

- 2 -

- 3 -

- 4 -

- 5 -

- 6 -

- 7 -

- 8 -

- 9 -

- 10 -

Table 1. Definitions and standard criteria of variables Definitions Standard criteria Dependent variables Prostate cancer Prevalence cases People already suffering from prostate cancer before the base line Incidence cases People suffering from prostate cancer after the base line Independent variables Common characteristics Age (yrs) <50, 50-59, 60-69, 70 Alcohol consumption No (Non-drinking), Yes (Past drinking and current drinking) Smoking status Non-smoker, Former smoker, Current smoker Exercise No, Yes Hypertension Received a diagnosis or medication or blood pressure 140/90mmHg Diabetes mellitus Received a diagnosis or medication or FBS * 126mg/dl Family history of prostate cancer No, Yes Clinical characteristics BMI (kg/m²) 18.5 SBP (mmhg) <120, 120-139, 140-159, 160 DBP (mmhg) <80, 80-89, 90-100, 100 FBS * (mg/dl) <100, 100-125, 126 Total cholesterol (mg/dl) <200, 200-239, 240 PSA (ng/dl) <3.0, 3.0 * FBS: Fasting blood sugar BMI: Body mass index SBP: Systolic blood pressure DBP: Diastolic blood pressure PSA: Prostate specific antigen - 11 -

- 12 -

- 13 -

- 14 -

Table 2. General characteristics of men in KCPS-II * KCPS-II * Variables (N=72,232) N mean±sd Age (yrs) 72,232 45.26±8.60 BMI (kg/m 2 ) 72,232 24.46±2.81 Weight (kg) 72,232 71.54±9.62 Height (cm) 72,232 170.90±5.83 SBP (mmhg) 70,879 121.75±13.52 DBP (mmhg) 70,880 76.88±9.96 FBS (mg/dl) 72,121 95.46±22.43 Total cholesterol (mg/dl) 72,066 194.29±33.77 PSA (ng/ml) 60,837 0.98±0.99 N % Smoking status Non smokers 19,454 28.16 Former smokers 20,420 29.55 Current smokers 29,219 42.29 Exercise No 21,914 32.16 Yes 46,237 67.84 Alcohol consumption No 9,296 13.43 Yes 59,927 86.57 Hypertension No 54,653 75.66 Yes 17,579 24.34 Diabetes mellitus No 66,528 92.10 Yes 5,704 7.90 Family history of prostate cancer No 71,946 99.60 Yes 286 0.40 * - 15 -

- 16 -

- 17 -

Table 2-1. General characteristics of men in KCPS-II * and KNHANES, 2007 Ageadjusted KCPS-II * KNHANES,2007 p (N=72,232) (N=1,124) p mean±sd Age (yrs) 45.26±8.60 54.76±13.28 <.001 - BMI (kg/m 2 ) 24.46±2.81 23.78±2.96 <.001 <.001 Weight (kg) 71.54±9.62 66.61±10.13 <.001 <.001 Height (cm) 170.90±5.83 167.15±6.63 <.001 <.001 SBP (mmhg) 121.75±13.52 122.57±16.60 0.120 0.001 DBP (mmhg) 76.88±9.96 79.14±10.28 <.001 <.001 FBS (mg/dl) 95.46±22.43 100.71±25.49 <.001 0.390 Total cholesterol (mg/dl) 194.29±33.77 188.65±34.50 <.001 <.001 % Smoking status Non smokers 28.16 15.52 Former smokers 29.55 44.15 Current smokers 42.29 40.32 Exercise No 32.16 57.38 Yes 67.84 42.62 Alcohol consumption No 13.43 31.55 Yes 86.57 68.45 * <.001 <.001 <.001 <.001 <.001 <.001-18 -

200 180 160 140 120 100 80 KCPS-II KNHANES,2007 60 40 20 0 Age(yrs) BMI(kg/m2) FBS (mg/dl) Total cholesterol (mg/dl) variables 100 90 80 70 60 50 40 KCPS-II KNHANES,2007 30 20 10 0 Smoking(Y) Exercise(Y) Alcohol(Y) variables - 19 -

- 20 -

Table 3. Prevalence and Incidence of prostate cancer in KCPS-II * (N,%) Observations Prevalence cases Incidence cases Total cases 72,232 45 (0.06) 160 (0.22) 205 (0.28) Table 4. Number of prostate cancer in KCPS-II *, 2004-2011 (N=72,232) Year Number of prostate cancer (N,%) ~2004 21 (10.24) 2005 17 (8.29) 2006 17 (8.29) 2007 30 (14.63) 2008 26 (12.68) 2009 27 (13.17) 2010 23 (11.22) 2011 44 (21.46) Total 205 (100.00) - 21 -

rostate cancer in KCPS-II, 2004-2011 Table 5. Number of prostate cancer by age groups in KCPS-II * (N,%) Number of Age (year) Observations prostate cancer <50 52,713 9 (0.02) 50-59 14,062 53 (0.38) 60-69 4,497 90 (2.00) 70 960 53 (5.52) Total 72,232 205 (0.28) - 22 -

Percentage of prostate cancer by age groups in KCPS-II Table 6. Number of prostate cancer by family history in KCPS-II * (N,%) Number of Family history Observations prostate cancer No 71,946 201 (0.28) Yes 286 4 (1.40) Total 72,232 205 (0.28) p-value 0.009-23 -

- 24 -

Table 7. Prevalence of prostate cancer in KCPS-II *, 2004-2011 (N=72,232) Year Prevalence of prostate cancer N % ~2000 6 13.33 2001 4 8.89 2002 3 6.67 2003 4 8.89 2004 1 2.22 2005 14 31.11 2006 8 17.78 2007 2 4.44 2008 2 4.44 2009 1 2.22 2010 0 0.00 2011 0 0.00 Total 45 100.00 Table 8. Prevalence of prostate cancer by age groups in KCPS-II * Age (year) Observations Number of (N) prostate cancer % <50 52,713 5 0.01 50-59 14,062 12 0.09 60-69 4,497 14 0.31 70 960 14 1.46 Total 72,232 45 0.06-25 -

- 26 -

Table 9. Incidence of prostate cancer in KCPS-II *, 2004-2011 (N=72,129) Year Number of prostate cancer % 2004 3 1.88 2005 3 1.88 2006 9 5.63 2007 28 17.50 2008 24 15.00 2009 26 16.25 2010 23 14.38 2011 44 27.50 Total 160 100.00 Table 10. Incidence of prostate cancer by age groups in KCPS-II * Number of Age (year) Observations (N) % prostate cancer <50 52,678 4 0.01 50-59 14,037 41 0.29 60-69 4,474 76 1.70 70 940 39 4.15 Total 72,129 160 0.22-27 -

- 28 -

Table 11. Prostate cancer incidence rates by age groups in KCPS-II * Age (year) Incidence Incidence Number of Observations Person per per prostate (N) year(py) 100,000 100,000 cancer(%) PY persons <50 72,678 231472.53 4 (0.01) 1.73 5.50 50-59 14,037 63282.35 41 (0.29) 64.79 292.09 60-69 4,474 21090.65 76 (1.70) 360.35 1698.70 70 940 4118.50 39 (4.15) 946.95 4148.94 Total 72,129 319964.03 160 (0.22) 50.01 221.82-29 -

- 30 -

- 31 -

Table 12. Age-standardized prostate cancer incidence rates in KCPS-II Age- Age- Observations (N) Prostate cancer incidence cases(%) Crude rate standardized incidence rates per 100,000 persons standardized incidence rates per 100,000PY 72,129 160 (0.22) 221.8 580.1 128.2 Table 13. Age-standardized prostate cancer incidence rates in KCPS-II and KCCR, 2011 Prostate cancer incidence cases(%) Crude rate Age-standardized prostate cancer incidence rates Year per 100,000 persons KCPS-II KCCR KCPS-II KCCR KCPS-II 1 2 KCCR 2011 44 (0.06) 8,952 (8.1) 61.0 35.7 98.0 134.5 27.5-32 -

Table 14. Age-standardized prostate cancer incidence rates in KCPS-II and KCCR, 2004-2011 Year Prostate cancer incidence cases(%) Agestandardized Crude rate prostate cancer incidence rates per 100,000 persons KCPS-II KCCR KCPS-II KCCR KCPS-II KCCR 2004 3 (0.08) 3,396 (4.6) 4.2 14.0 7.6 15.2 2005 3 (0.05) 3,727 (4.7) 4.2 15.3 11.0 15.9 2006 9 (0.06) 4,486 (5.4) 12.5 18.3 41.2 18.1 2007 28 (0.07) 5,516 (6.3) 38.8 22.4 98.6 21.0 2008 24 (0.03) 6,586 (7.0) 33.3 26.6 104.0 23.5 2009 26 (0.04) 7,455 (7.4) 36.0 30.0 98.5 25.2 2010 23 (0.03) 8,007 (7.6) 31.9 32.1 84.6 25.8 2011 44 (0.06) 8,952 (8.1) 61.0 35.7 134.5 27.5 2004-2011 160 36,516 221.8-580.1 - - 33 -

Figure 6. Age-standardized prostate cancer incidence rates in KCPS-II and KCCR, 2004-2011 - 34 -

- 35 -

Table 15. Age-specific prostate cancer incidence rate per 100,000 in KCPS-II and KCCR, 2011 Age in Number of Incidence per 100,000 persons Observations PSA 4.0 2011 prostate (N) (N) (year) cancer KCPS-II KCCR 35-39 5,989 11 0 0.0 0.2 40-44 20,777 114 0 0.0 0.9 45-49 15,555 100 2 12.9 3.2 50-54 12,083 75 4 33.1 12.6 55-59 8,085 99 12 148.4 40.4 60-64 4,601 77 8 173.9 114.7 65-69 2,606 81 12 460.5 227.2 70-74 1,559 71 4 256.6 315.2 75-79 664 43 2 301.2 386.7 80-84 166 12 0 0.0 383.3 85 44 4 0 0.0 282.8-36 -

- 37 -

- 38 -

Table 16. General characteristics of men with and without prostate cancer incidence in KCPS-II Prostate cancer Non-prostate incidence cancer (N=71,969) (N=160) p-value Mean±SD Age (year) 45.21±8.55 60.71±8.33 <.001 BMI (kg/m 2 ) 24.46±2.81 24.13±2.39 0.080 Weight (kg) 71.55±9.63 68.79±8.31 <.001 Height (cm) 170.91±5.83 168.73±5.35 <.001 SBP (mmhg) 121.73±13.51 128.66±15.70 <.001 DBP (mmhg) 76.87±9.96 78.90±10.44 0.010 FBS (mg/dl) 95.44±22.42 101.83±26.31 0.003 Total cholesterol (mg/dl) 194.31±33.76 191.01±31.60 0.220 PSA (ng/ml) 0.96±0.90 5.99±6.92 <.001 % Smoke Non smokers 28.14 35.10 Former smokers 29.51 41.72 Current smokers 42.35 23.18 Exercise No 32.18 24.32 Yes 67.82 75.68 Alcohol No 13.41 21.57 Yes 86.59 78.43 Hypertention No 75.73 55.63 Yes 24.27 44.38 Diabetes mellitus No 92.14 82.50 Yes 7.86 17.50 Family history No 99.61 98.75 Yes 0.39 1.25 <.001 0.050 0.005 <.001 <.001 0.130-39 -

- 40 -

- 41 -

Table 17. Hazard Ratios(HR) of prostate cancer in KCPS-II * (N=58,347) Observa tions(n) Person year (PY) Prostate cancer (N,%) Model 1 (N=124) HR (95%CI) Age (year) <50 43,940 188411.75 15 (12.10) 1.00 50-59 11,014 50215.35 47 (37.90) 7.91 (4.35-14.38) 60-69 2,909 14076.38 42 (33.87) 13.79 (7.32-25.96) 70 484 2180.80 20 (16.13) 25.61 (12.23-53.66) PSA (ng/ml) <3.0 57,007 248769.08 49 (0.09) 1.00 3.0 1,340 6115.20 75 (5.60) 26.44 (17.91-39.03) Hypertension Normal 18,413 82882.20 31 (25.00) 1.00 Pre 30,771 130482.80 54 (43.55) 1.04 (0.66-1.62) Stage1 7,239 32824.08 30 (24.19) 1.09 (0.65-1.82) Stage2 1,924 8695.20 9 (7.26) 1.26 (0.60-2.67) DM (Yes) 4,036 18069.60 20 (16.13) 1.21 (0.74-1.97) Dyslipidemia Normal 34,563 151248.22 70 (56.45) 1.00 Pre 18,729 81511.77 46 (37.10) 1.15 (0.79-1.67) Abnormal 5,055 22124.30 8 (6.45) 0.83 (0.40-1.73) Alcohol (Yes) 50,905 222635.98 99 (79.84) 1.23 (0.78-1.94) Smoke Non smokers 16,386 70008.63 41 (33.06) 1.00 Former smokers 17,297 77803.15 55 (44.35) 1.00 (0.66-1.52) Current smokers 24,664 107072.50 28 (22.58) 0.78 (0.47-1.29) Exercise (Yes) 40,377 174648.85 95 (76.61) 1.18 (0.78-1.80) Family history (Yes) 264 1072.85 2 (1.61) 13.17 (3.19-54.40) * - 42 -

- 43 -

- 44 -

Table 17-1. Hazard Ratios(HR) of prostate cancer stratified by age groups in KCPS-II * (N=58,347) Age<50 Age 50 N Prostate cancer Prostate cancer HR (95%CI) N cases(%) cases(%) HR (95%CI) Age (year) 43,940 15 (12.10) 1.35 (1.12-1.62) 14,407 109 (87.90) 1.07 (1.04-1.10) PSA (ng/ml) <3.0 43,295 8 (53.33) 1.00 13,712 41 (37.61) 1.00 3.0 645 7 (46.67) 48.31 (16.29-143.29) 695 68 (62.39) 23.00 (15.24-34.71) Hypertension Normal 14,559 2 (13.33) 1.00 3,854 29 (26.61) 1.00 Pre 23,465 7 (46.67) 4.85 (0.90-26.06) 7,306 47 (43.12) 0.91 (0.57-1.45) Stage1 4,659 4 (26.67) 6.38 (1.09-37.48) 2,580 26 (23.85) 0.91 (0.53-1.56) Stage2 1,257 2 (13.33) 7.65 (0.97-60.20) 667 7 (6.42) 0.98 (0.43-2.25) DM (Yes) 2,121 2 (13.33) 1.79 (0.37-8.59) 1,915 18 (16.51) 1.09 (0.65-1.82) * - 45 -

(continued) Age<50 Age 50 N Prostate cancer Prostate cancer HR (95%CI) N cases(%) cases(%) HR (95%CI) Dyslipidemia Normal 26,191 7 (46.67) 1.00 8,372 63 (57.80) 1.00 Pre 13,972 6 (40.00) 1.53 (0.51-4.63) 4,757 40 (36.70) 1.10 (0.74-1.64) Abnormal 3,777 2 (13.33) 2.22 (0.44-11.38) 1,278 6 (5.50) 0.71 (0.31-1.65) Alcohol (Yes) 39,274 13 (86.67) 0.55 (0.12-2.54) 11,631 86 (78.90) 1.35 (0.84-2.18) Smoke Non smokers 12,125 4 (26.67) 1.00 4,261 37 (33.94) 1.00 Former smokers 11,688 7 (46.67) 1.72 (0.47-6.23) 5,609 48 (44.04) 0.91 (0.59-1.41) Current smokers 20,127 4 (26.67) 0.77 (0.19-3.23) 4,537 24 (22.02) 0.81 (0.48-1.39) Exercise (Yes) 29,691 11 (73.33) 1.22 (0.38-3.96) 10,686 84 (77.06) 1.17 (0.75-1.83) Family history (Yes) 232 1 (6.67) 53.93 (6.33-459.79) 32 1 (0.92) 11.03 (1.51-80.64) * - 46 -

- 47 -

- 48 -

Table 17-2. Hazard Ratios(HR) of prostate cancer according to diagnosis of DM * in KCPS-II (N=58,347) Non-DM * DM * N Prostate cancer Prostate cancer HR (95%CI) N cases(%) cases(%) HR (95%CI) Age (year) <50 41,819 13 (12.50) 1.00 2,121 2 (10.00) 1.00 50-59 9,710 41 (39.42) 9.03 (4.75-17.17) 1,304 6 (60.00) 2.50 (0.48-12.91) 60-69 2,387 34 (32.69) 15.49 (7.79-30.81) 522 8 (40.00) 5.47 (1.08-27.81) 70 395 16 (15.38) 29.76 (13.28-66.69) 89 4 (20.00) 5.48 (0.83-36.16) PSA (ng/ml) <3.0 53,093 40 (38.46) 1.00 3,914 9 (45.00) 1.00 3.0 1,218 64 (61.54) 29.77 (19.39-45.72) 122 11 (55.00) 22.92 (8.47-62.01) Hypertension Normal 17,584 27 (25.96) 1.00 829 4 (20.00) 1.00 Pre 28,579 49 (47.12) 1.12 (0.70-1.80) 2,192 5 (25.00) 0.64 (0.17-2.42) Stage1 6,459 21 (20.19) 0.97 (0.54-1.74) 780 9 (45.00) 1.81 (0.54-6.06) Stage2 1,689 7 (6.73) 1.09 (0.47-2.53) 235 2 (10.00) 2.51 (0.43-14.65) * - 49 -

(continued) Non-DM * DM * N Prostate cancer Prostate cancer HR (95%CI) N cases(%) cases(%) HR (95%CI) Dyslipidemia Normal 32,339 55 (52.88) 1.00 2,224 15 (75.00) 1.00 Pre 17,409 42 (40.38) 1.34 (0.90-2.01) 1,320 4 (20.00) 0.69 (0.22-2.18) Abnormal 4,563 7 (6.73) 0.95 (0.43-2.08) 492 1 (5.00) 0.42 (0.05-3.56) Alcohol (Yes) 47,424 82 (78.85) 1.12 (0.68-1.84) 3,481 17 (85.00) 3.00 (0.77-11.68) Smoke Non smokers 15,432 30 (28.85) 1.00 954 11 (55.00) 1.00 Former smokers 15,945 48 (46.15) 1.32 (0.83-2.12) 1,352 7 (35.00) 0.27 (0.10-0.73) Current smokers 22,934 26 (25.00) 1.07 (0.62-1.85) 1,730 2 (10.00) 0.15 (0.03-0.74) Exercise (Yes) 37,371 77 (74.04) 1.03 (0.66-1.60) 3,006 18 (90.00) 3.12 (0.69-14.05) Family history (Yes) 255 2 (1.92) 18.71 (4.48-78.14) 9 0 - * - 50 -

- 51 -

Table 18. Concentrations of PSA * by age groups Age (year) Observations (N) Prostate cancer cases(%) Mean±SD PSA * (ng/ml) Min-Max 95 percentile 40-49 26,113 16(0.06) 0.9±0.7 0.1-19.9 1.9 50-59 11,551 47(0.41) 1.0±0.9 0.0-21.4 2.4 60-69 3,243 46(1.42) 1.5±2.7 0.0-104.3 4.0 70-79 523 22(4.21) 2.0±2.6 0.1-28 5.6 80-89 33 0 2.1±2.1 0.4-10.5 7.0 35-89 60,753 131(0.22) 1.0±1.0 0-104.3 2.1 * - 52 -

- 53 -

Table 18-1. Age-specific PSA * cut-off levels for prostate cancer Age (year) PSA * cutpoint (ng/ml) Sensitivity (%) Specificity (%) AUC-ROC (95% CI) 40-49 1.9 87.50 94.01 0.9418 (0.8838-0.9998) 50-59 1.9 82.98 90.79 0.9311 (0.9005-0.9618) 60-69 1.9 86.96 80.89 0.9009 (0.8500-0.9518) 70-79 2.1 86.36 74.85 0.8929 (0.8415-0.9443) 80-89 NA... 35-89 1.7 89.31 90.50 0.9476 (0.9287-0.9665) * Figure 7. ROC curve of age-specific PSA levels for prostate cancer - 54 -

- 55 -

- 56 -

- 57 -

- 58 -

- 59 -

- 60 -

- 61 -

- 62 -

- 63 -

- 64 -

- 65 -

- 66 -

- 67 -

- 68 -

Table 19. Comparison of age-specific PSA * cut-off levels among White, Chinese and Korean men PSA * (ng/ml) cut-off levels (95th percentile) Age (year) Korean Chinese White Present Study (Choi YD,2007) (Liu ZY,2009) (Oesterling,1993) 40-49 1.9 1.92 2.15 2.5 50-59 2.4 2.37 3.20 3.5 60-69 4.0 3.56 4.10 4.5 70-79 5.6 5.19 5.37 6.5 * - 69 -

- 70 -

- 71 -

- 72 -

- 73 -

- 74 -

- 75 -

- 76 -

fi - 77 -

fi fi - 78 -

- 79 -

- 80 -

- 81 -

- 82 -

- 83 -