Coffee Consumption and Prostate Cancer Risk and Progression in the Health Professionals Follow-up Study

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

Disclosures

J Natl Cancer Inst. 2011;103(11):876-884. 

In This Article

Discussion

In this large prospective study, coffee intake was weakly inversely associated with overall risk of prostate cancer, but it was associated with statistically significantly lower risk of lethal and advanced prostate cancers, with those who drank the most coffee having less than half the risk of these outcomes as nondrinkers. Coffee was not associated with nonadvanced or low-grade cancer and only weakly inversely associated with high-grade cancers. Inverse associations with lethal and advanced disease were similar for regular and decaffeinated coffee. The associations were stronger for more recent coffee exposure, suggesting possible effects later in the development of advanced prostate cancers.

The characteristics of heavy coffee drinkers make it unlikely that confounding is a major explanation for these findings because coffee drinkers were more likely to smoke and less likely to engage in vigorous exercise, behaviors which may increase advanced prostate cancer risk. Therefore, confounding by smoking and other lifestyle factors would bias the associations toward the null, rather than explaining the inverse associations for coffee that we observed. In addition, PSA testing was similar for high coffee consumers and nonconsumers, and results were similar in pre-PSA and PSA eras. Thus, PSA screening is an unlikely explanation for these associations.

Reverse causation is a possible explanation for these findings. Men with undiagnosed prostate cancer might decrease their consumption of coffee due to urinary symptoms. However prostate cancer often produces no urinary symptoms, because most tumors arise in the peripheral zone of the gland.[35] Indeed, we found no association between lower urinary tract symptoms and coffee intake. Moreover, in subanalyses to explore reverse causation, the association between coffee and risk of advanced or lethal prostate cancer remained statistically significant. Thus, reverse causation does not appear to explain the association.

Previous studies of coffee and prostate cancer have generally not reported the striking inverse associations that we observed.[16–32] However, all but two studies reported findings only for overall prostate cancer, potentially overlooking inverse associations with advanced disease. Several studies were limited by a narrow range in coffee intakes, small numbers of case subjects, and lack of adjustment for smoking; confounding by smoking could obscure an inverse association because smoking is associated with coffee consumption in many populations and is also associated with prostate cancer–specific mortality.[36]

Prostate cancer mortality, an outcome more comparable to our lethal disease, was examined in two cohorts.[31,32] Both adjusted only for age as a potential confounder. The Seventh-day Adventists cohort[31] found a relative risk of 0.70 for men drinking two or more cups per day compared with nondrinkers, based on 93 cancer deaths. Hsing et al.[32] found no association between coffee and prostate cancer death in the Lutheran Brotherhood cohort, based on 149 deaths (≥5 cups per day vs reference <3 cups daily: RR = 1.0, 95% CI = 0.6 to 1.6). The results from both studies are compatible with our findings for lethal prostate cancer, given the wide confidence intervals, differing categorizations of intake, and lack of control for smoking. Smoking is likely less of an issue in the Seventh-day Adventists cohort (a population with very low smoking rates), which observed results closer to ours. However, the range of exposures was low in this cohort, with only 5% of men consuming more than two cups of coffee daily.

Three prospective cohort studies found no statistically significant associations between coffee intake and prostate cancer incidence. Two reports from a cohort of 8000 Japanese men in Hawaii found no association, based on 174 incident cancers.[16,17] Another Hawaiian cohort[18] also found no association, though coffee intake was low, such that the highest category was greater than 2.5 cups per day. A Norwegian cohort[19] that included 260 men with prostate cancer found a statistically nonsignificant relative risk of 0.74 for men who consumed seven or more cups per day compared with men who consumed two or fewer cups. The Norwegian study[19] was the only prospective cohort to adjust for smoking.

Five population-based and two hospital-based case–control studies found no association of coffee intake and overall prostate cancer incidence,[20–24,29,30] whereas two hospital-based studies[25,26] found increased risks of prostate cancer with higher coffee intake. A small retrospective cohort study in Canada[27] and a prospective case–control study in Sweden[28] found positive associations between coffee and prostate cancer, but these were not statistically significant and the confidence intervals were wide in both studies. None of the studies that found positive associations were adjusted for smoking, thus confounding is a major concern in these studies. Case–control studies are also prone to selection and recall bias.

An association between coffee and lower risk of advanced prostate cancer is biologically plausible. Coffee improves glucose metabolism, has anti-inflammatory and antioxidant effects, and affects sex hormone levels, all of which play roles in prostate cancer progression.

Coffee contains chlorogenic acids (CGAs), which inhibit glucose absorption in the intestine and may favorably alter levels of gut hormones, which affect insulin response.[1] Quinides, the roasting products of CGAs, inhibit liver glucose production in experimental models.[1] Coffee also contains lignans, phytoestrogens with potent antioxidant activity, which may have positive effects on glucose handling.[37] In humans, coffee drinking has been cross-sectionally associated with lower glucose levels after oral glucose loads and better insulin sensitivity.[38–40] A cross-sectional study in women found a negative correlation between coffee consumption and circulating C-peptide, a marker of insulin secretion.[41]

Insulin may promote tumor progression through the insulin and insulin-like growth factor 1 (IGF-1) receptors in cancer cells. Insulin levels have been associated with a greater risk of cancer progression or mortality among men diagnosed with prostate cancer,[9–11] even though insulin has been unassociated[12,13] or inversely associated[14] with overall incidence.

Coffee is a major source of antioxidants and is estimated to provide half of total antioxidant intake in several populations.[2,3] Coffee has been associated with improved markers of inflammation in cross-sectional studies and in a recent trial.[4,42,43] Inflammation is hypothesized to play a role in the development of prostate cancer through the generation of proliferative inflammatory atrophy lesions.[15] Various dietary antioxidants may reduce inflammation and have been associated with lower risk of advanced prostate cancer.[44,45]

Coffee drinking may be associated with increased sex hormone–binding globulin (SHBG) and total testosterone levels.[5] One study in Greek men found a positive association with estradiol levels but not with SHBG or testosterone,[6] whereas another found no association between coffee and sex hormones in young Greek men.[7] Coffee has been consistently associated with higher SHBG levels in women.[46–49]

Sex hormones play a role in prostate cancer, though the relationships between circulating levels within normal ranges and risk have been difficult to elucidate. It has been hypothesized that although testosterone is necessary for the initial development of prostate cancer, it may limit progression of the disease.[50,51] A pooled analysis of 18 prospective studies found an inverse association between SHBG levels and prostate cancer risk.[51]

Strengths of our study include the prospective and updated assessment of coffee, long follow-up, and a large number of incident prostate cancers, which allowed us to study stage- and grade-based subtypes. The range of intakes in this cohort was wide, with 16% of men consuming no coffee and 19% of men consuming four or more cups per day. Coffee was accurately reported on FFQs,[33] and any misclassification in coffee intake due to differences in cup size or brewing strength would be expected to bias observed associations toward the null and thus would not explain the inverse associations that we observed. Our use of repeated measures of diet over time captured changes in diet and reduced measurement error;[52] however, we were not able to assess coffee intake in young adulthood or total lifetime coffee intake.

This study also has some limitations. First, we relied on self-reported diet, which will inevitably be imperfect. Although coffee is well reported, we assessed usual intake only every 4 years, thus missing shorter-term fluctuations in intakes. In addition, we do not have coffee intake information from earlier periods of life, limiting our ability to determine the most relevant time periods of exposure. Finally, although reverse causation does not appear to explain our findings, we cannot rule it out as a possible source of bias.

In conclusion, men who consumed coffee regularly had a reduced risk of lethal or advanced prostate cancer. It is premature to recommend that men increase coffee intake to reduce advanced prostate cancer risk based on this single study. In addition, the effects of coffee consumption on other aspects of health must be considered in making consumption recommendations. However, our findings are potentially important, given the lack of identified modifiable risk factors for advanced prostate cancer. The association between coffee and prostate cancer should be studied in other prospective cohorts with a wide range of coffee intakes, with control for smoking, and evaluation of lethal or advanced cancers.

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