Coffee and Prostate Cancer – Get into it

Sep 14, 2011

Abstract and Introduction

Abstract

Background Coffee contains many biologically active compounds, including caffeine and phenolic acids, that have potent antioxidant activity and can affect glucose metabolism and sex hormone levels. Because of these biological activities, coffee may be associated with a reduced risk of prostate cancer.
Methods We conducted a prospective analysis of 47 911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter. From 1986 to 2006, 5035 patients with prostate cancer were identified, including 642 patients with lethal prostate cancers, defined as fatal or metastatic. We used Cox proportional hazards models to assess the association between coffee and prostate cancer, adjusting for potential confounding by smoking, obesity, and other variables. All P values were from two-sided tests.
Results The average intake of coffee in 1986 was 1.9 cups per day. Men who consumed six or more cups per day had a lower adjusted relative risk for overall prostate cancer compared with nondrinkers (RR = 0.82, 95% confidence interval [CI] = 0.68 to 0.98, P trend = .10). The association was stronger for lethal prostate cancer (consumers of more than six cups of coffee per day: RR = 0.40, 95% CI = 0.22 to 0.75, P trend = .03). Coffee consumption was not associated with the risk of nonadvanced or low-grade cancers and was only weakly inversely associated with high-grade cancer. The inverse association with lethal cancer was similar for regular and decaffeinated coffee (each one cup per day increment: RR = 0.94, 95% CI = 0.88 to 1.01, P = .08 for regular coffee and RR = 0.91, 95% CI = 0.83 to 1.00, P = .05 for decaffeinated coffee). The age-adjusted incidence rates for men who had the highest (≥6 cups per day) and lowest (no coffee) coffee consumption were 425 and 519 total prostate cancers, respectively, per 100 000 person-years and 34 and 79 lethal prostate cancers, respectively, per 100 000 person-years.
Conclusions We observed a strong inverse association between coffee consumption and risk of lethal prostate cancer. The association appears to be related to non-caffeine components of coffee.

Introduction

Coffee contains diverse biologically active compounds that include caffeine, minerals, and phytochemicals. Long-term coffee drinking has been associated with improved glucose metabolism and insulin secretion in observational and animal studies.[] Coffee is also a potent antioxidant[2–4] and may be associated with sex hormone levels.[5–7]

Coffee consumption has been consistently associated with a reduced risk of type 2 diabetes,[] and its effects on insulin, sex hormones, and antioxidants may also be relevant to prostate cancer. We hypothesized that coffee may be associated with lower risk of more advanced prostate cancers because the associations of insulin, antioxidants, and androgens with incidence of prostate cancer are stronger for advanced disease than for overall disease.[9–15]

Epidemiological studies of coffee consumption and prostate cancer have generally reported null results,[16–30] although most lacked a wide range of coffee intakes and a large number of case subjects and none specifically examined advanced disease. The two studies of coffee consumption and prostate cancer mortality[31,32] found no statistically significant associations, but these were limited by a narrow range of intake, small number of cancer deaths, and inadequate adjustment for potential confounding.

We investigated the relationship between coffee intake and risk of overall prostate cancer and of aggressive disease, defined as lethal, advanced, or high-grade cancer, in the Health Professionals Follow-up Study.

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Table 1. Age-adjusted characteristics of the Health Professionals Follow-up Study population at baseline in 1986, by coffee consumption*

Characteristic Category of total coffee intake
None (n = 7890) <1 cup per day (n = 9533) 1–3 cups per day (n = 21 261) 4–5 cups per day (n = 6735) ≥6 cups day (n = 2492)
Mean age, y 52 55 55 54 53
White race, % 95 94 96 98 98
Mean BMI, kg/m2 25 25 26 26 26
Mean BMI at age 21, kg/m2 23 23 23 23 23
Mean height, inches 70 70 70 70 70
Former smoker, quit >10 y ago, % 20 28 32 34 31
Former smoker, quit ≤10 y ago, % 6 10 14 17 17
Current smokers, % 4 6 10 16 25
Vigorous activity (% highest quintile) 17 17 15 15 11
Diabetes, % 3 3 3 3 3
Family history of prostate cancer, % 13 11 12 12 12
PSA test, 1994, % 35 39 38 38 33
PSA test, 2004, % 60 64 66 66 58
Mean dietary intakes
   Energy, kcal/d 1960 1895 1990 2069 2159
   Alcohol, g/d 6 9 13 14 15
   Calcium, mg/d 973 931 866 881 873
   Alpha-linolenic acid, g/d 1.1 1.1 1.1 1.1 1.1
   Supplemental vitamin E, mg/day 41.5 45.1 36.1 33.3 33.0
   Multivitamin use, % 42 44 41 40 38
   Processed meat, servings per week 2.1 2.1 2.6 2.9 3.4
   Tomato sauce, servings per week 0.9 0.9 0.9 0.9 0.9
   Total coffee, servings per day 0.0 0.5 1.9 4.2 6.3
   Regular coffee, servings per day 0.0 0.2 1.3 2.9 4.2
   Decaffeinated coffee, servings per day 0.0 0.2 0.6 1.3 2.0

* All variables (except age) are standardized to the age distribution of the cohort at baseline. BMI = body mass index; PSA = prostate-specific antigen.

Table 2. Relative risk (RR) with 95% confidence interval (95% CI) of prostate cancer by category of total coffee intake, 1986–2006*

Risk of prostate cancer Category of coffee intake P trend
None <1 cup/d 1–3 cups/d 4–5 cups/d ≥6 cups/d
All prostate cancers, No. 587 1139 2438 719 152
   Age-adjusted RR (95% CI) 1.00 0.96 (0.87 to 1.06) 0.97 (0.88 to 1.06) 0.95 (0.85 to 1.06) 0.81 (0.67 to 0.96) .08
   Fully adjusted RR (95% CI) 1.00 0.94 (0.85 to 1.05) 0.94 (0.86 to 1.04) 0.93 (0.83 to 1.04) 0.82 (0.68 to 0.98) .10
Lethal prostate cancers†, No. 89 150 298 93 12
   Age-adjusted RR (95% CI) 1.00 0.76 (0.58 to 0.99) 0.73 (0.58 to 0.93) 0.83 (0.62 to 1.11) 0.43 (0.24 to 0.80) .08
   Fully adjusted RR (95% CI) 1.00 0.76 (0.58 to 1.00) 0.71 (0.55 to 0.92) 0.76 (0.56 to 1.04) 0.40 (0.22 to 0.75) .03
Advanced prostate cancers†, No. 122 211 422 122 19
   Age-adjusted RR (95% CI) 1.00 0.81 (0.65 to 1.02) 0.78 (0.63 to 0.95) 0.79 (0.61 to 1.01) 0.49 (0.30 to 0.80) .01
   Fully adjusted RR (95% CI) 1.00 0.81 (0.64 to 1.02) 0.75 (0.60 to 0.93) 0.73 (0.56 to 0.95) 0.47 (0.28 to 0.77) .004
Nonadvanced prostate cancers†, No. 353 729 1554 483 102
   Age-adjusted RR (95% CI) 1.00 1.04 (0.91 to 1.18) 1.04 (0.92 to 1.16) 1.04 (0.91 to 1.20) 0.88 (0.71 to 1.10) .60
   Fully adjusted RR(95% CI) 1.00 1.01 (0.88 to 1.15) 0.99 (0.87 to 1.12) 1.02 (0.88 to 1.18) 0.93 (0.74 to 1.16) .77
Grade 8–10 cancers, No. 61 111 255 78 11
   Age-adjusted RR (95% CI) 1.00 0.86 (0.63 to 1.18) 0.93 (0.70 to 1.23) 0.96 (0.69 to 1.35) 0.57 (0.30 to 1.09) .58
   Fully adjusted RR (95% CI) 1.00 0.84 (0.61 to 1.16) 0.87 (0.65 to 1.18) 0.88 (0.61 to 1.26) 0.53 (0.27 to 1.02) .29
Grade 7 cancers, No. 174 295 641 226 41
   Age-adjusted RR (95% CI) 1.00 0.86 (0.72 to 1.04) 0.88 (0.74 to 1.04) 0.98 (0.80 to 1.20) 0.69 (0.49 to 0.97) .58
   Fully adjusted RR (95% CI) 1.00 0.85 (0.70 to 1.04) 0.85 (0.71 to 1.02) 0.94 (0.76 to 1.16) 0.69 (0.49 to 0.99) .50
Grade 2–6 cancers, No. 232 489 1045 298 70
   Age-adjusted RR (95% CI) 1.00 1.08 (0.92 to 1.26) 1.07 (0.93 to 1.24) 0.99 (0.83 to 1.18) 0.94 (0.72 to 1.23) .34
   Fully adjusted RR (95% CI) 1.00 1.02 (0.87 to 1.20) 1.01 (0.87 to 1.18) 0.96 (0.80 to 1.15) 1.00 (0.75 to 1.31) .53

* All relative risks are from an age-adjusted model adjusted for age in months and calendar time. The multivariable model was additionally adjusted for: race (White, African American, Asian American, Other), height (quartiles), BMI at age 21 (<20, 20 to <22.5, 22.5 to <25, ≥25), current BMI (<21, 21 to <23, 23 to <25, 25 to <27.5, 27.5 to <30, ≥30 kg/m2), vigorous physical activity (quintiles), smoking (never, former quit >10 years ago, former quit <10 years ago, current), diabetes (type I or II, yes/no), family history of prostate cancer in father or brother (yes/no), multivitamin use (yes/no), intakes of processed meat, tomato sauce, calcium, alpha linolenic acid, supplemental vitamin E, alcohol intake (all quintiles), and energy intake (continuous), and history of PSA testing (yes/no, lagged by one period to avoid counting diagnostic PSA tests as screening; collected frsom 1994 onwards). All P values were from two-sided tests. BMI = body mass index; PSA, prostate-specific antigen.
† Lethal prostate cancer: Prostate cancer death or bone metastases at diagnosis or during follow-up. Advanced: Lethal, or stage T3b, T4, N1, or M1 at diagnosis, or spread to lymph nodes or other metastases during follow-up. Nonadvanced: T1 or T2 and N0/M0 at diagnosis with no spread to lymph nodes or other metastases or death during follow-up.

Table 3. Relative risk (RR) and 95% confidence interval (95% CI) of prostate cancer by category of regular coffee intake*

Risk of prostate cancer No coffee at all† Category of regular (with caffeine) coffee intake P trend No regular, some decaf
<1 cup per day 1–3 cups per day 4–5 cups per day ≥6 cups per day
Lethal prostate cancers‡, No. 89 207 209 52 6 79
Fully adjusted RR (95% CI)* 1.00 0.81 (0.61 to 1.07) 0.71 (0.54 to 0.93) 0.77 (0.53 to 1.10) 0.46 (0.20 to 1.08) .07 0.72 (0.51 to 1.01)
Advanced prostate cancers‡, No. 122 298 293 65 12 106
Fully adjusted RR (95% CI)* 1.00 0.86 (0.69 to 1.09) 0.74 (0.59 to 0.93) 0.70 (0.51 to 0.95) 0.69 (0.38 to 1.27) .01 0.75 (0.56 to 1.00)
Nonadvanced prostate cancers‡, No. 353 1042 1164 270 43 349
Fully adjusted RR (95% CI)* 1.00 0.98 (0.86 to 1.12) 0.99 (0.87 to 1.12) 1.00 (0.84 to 1.18) 0.93 (0.67 to 1.29) .97 1.10 (0.93 to 1.29)

* All relative riskss are from a multivariable model adjusted for: age in months, calendar time, race (White, African American, Asian American, Other), height (quartiles), BMI at age 21 (four categories), current BMI (six categories), vigorous physical activity (quintiles), smoking (never, former quit >10 years ago, former quit <10 years ago, current), diabetes (type I or II, yes/no), family history of prostate cancer in father or brother (yes/no), multivitamin use (yes/no), intakes of processed meat, tomato sauce, calcium, alpha linolenic acid, supplemental vitamin E, alcohol intake (all quintiles), energy intake (continuous), and history of prostate-specific antigen testing. Models for regular coffee are also adjusted for decaffeinated coffee intake (continuous). All P values are from two-sided tests. BMI = body mass index.
† Reference group is men who drink no regular or decaffeinated coffee.
‡ Lethal prostate cancer: Prostate cancer death or bone metastases at diagnosis or during follow-up. Advanced: Lethal, or stage T3b, T4, N1, or M1 at diagnosis, or spread to lymph nodes or other metastases during follow-up. Nonadvanced: T1 or T2 and N0/M0 at diagnosis with no spread to lymph nodes or other metastases or death during follow-up.

Table 4. Relative risk (RR) and 95% confidence interval (CI) of prostate cancer by category of decaffeinated coffee intake*

No coffee at all† Category of decaffeinated coffee intake P trend No decaf, some regular
<1 cup/d 1–3 cups/d ≥4 cups/d
Lethal prostate cancers‡, No. 89 264 125 15 149
Fully adjusted RR* 1.00 0.81 (0.62 to 1.06) 0.68 (0.50 to 0.91) 0.53 (0.30 to 0.94) .01 0.71 (0.52 to 0.98)
Advanced prostate cancers‡, No 122 374 171 25 204
Fully adjusted RR* 1.00 0.85 (0.68 to 1.07) 0.70 (0.54 to 0.89) 0.67 (0.43 to 1.05) .02 0.77 (0.59 to 1.01)
Nonadvanced prostate cancers‡, No. 353 1455 688 86 639
Fully adjusted RR* 1.00 0.99 (0.87 to 1.13) 1.04 (0.90 to 1.19) 0.94 (0.74 to 1.20) .88 0.98 (0.85 to 1.14)

* All relative riskss are from a multivariable model adjusted for: age in months, calendar time, race (White, African American, Asian American, Other), height (quartiles), BMI at age 21 (four categories), current BMI (six categories), vigorous physical activity (quintiles), smoking (never, former quit >10 years ago, former quit <10 years ago, current), diabetes (type I or II, yes/no), family history of prostate cancer in father or brother (yes/no), multivitamin use (yes/no), intakes of processed meat, tomato sauce, calcium, alpha linolenic acid, supplemental vitamin E, alcohol intake (all quintiles), and energy intake (continuous), and history of prostate-specific antigen testing. Models for decaffeinated coffee are also adjusted for regular coffee intake (continuous). All P values are from two-sided tests. BMI = body mass index.
† Reference group is men who drink no regular or decaffeinated coffee. ‡ Lethal prostate cancer: Prostate cancer death or bone metastases at diagnosis or during follow-up. Advanced: Lethal, or stage T3b, T4, N1 or M1 at diagnosis, or spread to lymph nodes or other metastases during follow-up. Nonadvanced: T1 or T2 and N0/M0 at diagnosis with no spread to lymph nodes or other metastases or death during follow-up.

Table 5. Relative risk (RR) and 95% confidence interval (95% CI) of prostate cancer by category of total coffee intake for various latency periods between exposure and diagnosis*

Total prostate cancer Advanced cancer† Nonadvanced cancer†
N RR (95% CI) N RR (95% CI) N RR (95% CI)
0 to 4-year lag, cups per day
   None 810 1.00 (referent) 160 1.00 (referent) 493 1.00 (referent)
   <1 1003 .95 (.87 to 1.05) 180 .78 (.62 to.97) 655 1.05 (.93 to 1.18)
   1–3 2501 .96 (.89 to 1.05) 436 .77 (.63 to.93) 1592 1.01 (.91 to 1.13)
   4–5 587 .97 (.87 to 1.09) 100 .73 (.56 to.95) 389 1.08 (.93 to 1.24)
   ≥6 134 .81 (.67 to.98) 20 .52 (.33 to.84) 92 .96 (.76 to 1.21)
   P trend .20 .008 .91
4 to 8-year lag, cups per day
   None 745 1.00 (referent) 131 1.00 (referent) 468 1.00 (referent)
   <1 886 .92 (.83 to 1.02) 152 .84 (.66 to 1.07) 589 1.00 (.88 to 1.13)
   1–3 2267 .93 (.85 to 1.02) 329 .72 (.58 to.89) 1519 1.00 (.89 to 1.11)
   4–5 594 .92 (.82 to 1.03) 99 .81 (.61 to 1.07) 397 .97 (.85 to 1.12)
   ≥6 153 .80 (.67 to.96) 18 .47 (.28 to.78) 102 .88 (.71 to 1.10)
   P trend .06 .008 .34
8 to 12-year lag, cups per day
   None 551 1.00 (referent) 79 1.00 (referent) 360 1.00 (referent)
   <1 664 .98 (.87 to 1.10) 91 .85 (.62 to 1.17) 458 1.06 (.92 to 1.22)
   1–3 1687 .99 (.89 to 1.10) 181 .68 (.51 to.91) 1175 1.06 (.93 to 1.20)
   4–5 465 .91 (.80 to 1.03) 63 .82 (.58 to 1.17) 329 .98 (.83 to 1.14)
   ≥6 154 .93 (.77 to 1.12) 18 .71 (.42 to 1.21) 111 1.04 (.83 to 1.30)
   P trend .17 .18 .70
12 to 16-year lag, cups per day
None 389 1.00 (referent) 41 1.00 (referent) 268 1.00 (referent)
   <1 448 .97 (.84 to 1.11) 49 .90 (.58 to 1.39) 307 .96 (.81 to 1.14)
   1–3 1046 .93 (.82 to 1.06) 93 .72 (.48 to 1.07) 742 .94 (.81 to 1.10)
   4–5 353 .97 (.83 to 1.13) 41 .97 (.61 to 1.55) 260 1.02 (.85 to 1.23)
   ≥6 115 .93 (.75 to 1.16) 8 .59 (.27 to 1.29) 84 .98 (.76 to 1.26)
   P trend .61 .43 .78

* All relative riskss are from multivariable models adjusted for: age in months, calendar time, race (White, African American, Asian American, Other), height (quartiles), BMI at age 21 (<20, 20 to <22.5, 22.5 to <25, .25 kg/m2), current BMI (<21, 21 to <23, 23 to <25, 25 to <27.5, 27.5 to <30, .30 kg/m2), vigorous physical activity (quintiles), smoking (never, former quit >10 years ago, former quit <10 years ago, current), diabetes (type I or II, yes/no), family history of prostate cancer in father or brother (yes/no), multivitamin use (yes/no), intakes of processed meat, tomato sauce, calcium, alpha linolenic acid, supplemental vitamin E, alcohol intake (all quintiles), and energy intake (continuous), and history of PSA testing (yes/no, lagged by one period to avoid counting diagnostic PSA tests as screening; collected from 1994 onwards). All P values are from two-sided tests. BMI = body mass index; PSA = prostate-specific antigen.
† Advanced: Lethal, or stage T3b, T4, N1, or M1 at diagnosis, or spread to lymph nodes or other metastases during follow-up. Nonadvanced: T1 or T2 and N0/M0 at diagnosis with no spread to lymph nodes or other metastases or death during follow-up.

Authors and Disclosures

Kathryn M. Wilson, Julie L. Kasperzyk, Jennifer R. Rider, Stacey Kenfield, Rob M. van Dam, Meir J. Stampfer, Edward Giovannucci and Lorelei A. Mucci

Department of Epidemiology (KMW, JLK, SK, MJS, EG, LAM) and Department of Nutrition (RMvD, MJS, EG), Harvard School of Public Health, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (KMW, JLK, JRR, SK, MJS, EG, LAM); Department of Urology, Örebro University Hospital, Örebro, Sweden (JRR); Department of Epidemiology and Department of Public Health and Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (RMvD)

Correspondence to
Kathryn M. Wilson, ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115 (e-mail: kwilson@hsph.harvard.edu).

via medscape.com

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