We found that increased coffee intake was associated with reduced risk of aggressive PC but no significant relationship with either low grade (Gleason
7), intermediate grade (Gleason
7) and overall risk of developing PC in this population-based prospective cohort study. The men who drank 3 or more cups of coffee had 55% lower risk of developing aggressive disease (Gleason
7). The overall null association between coffee consumption and PC incidence was consistent with many epidemiological studies [17
]. Furthermore, inverse association between coffee and aggressive PC was fairly consistent with recently reported findings from Health Professional Follow-up Study, where a risk reduction of 47% was observed among high coffee consumers [20
]. We are unaware of any other studies reporting the grade-specific PC risk in relation to coffee consumption.
The demographic and lifestyle characteristics of high coffee drinkers i.e. higher social class, desirable BMIs and current smoking, make it unlikely that confounding is a major explanation for these findings. Confounding by smoking and other lifestyle factors would bias the results towards null rather than an inverse association, which we report. It might be hypothesised that reverse causality might explain the protective effect of coffee on PC reported elsewhere. That is, men with undiagnosed PC may reduce their fluid intake, including coffee, to reduce symptoms of polyuria. Thus, PC would be less frequent among men who drank more coffee. However, PC often produces no urinary symptoms because most of the tumours arise in the peripheral zone of the prostate gland [26
]. In addition, we conducted analyses to assess possible reverse causation by excluding individuals who were diagnosed in the first 10
years of screening, interestingly the association between coffee and overall risk of PC, exaggerated after excluding men who were diagnosed in first 10
years of follow-up, although remained non-significant.
Several biological mechanisms have been proposed which may explain the inverse association between high coffee consumption and aggressive PC. Coffee consumption can lower the insulin-like growth factor-1 (IGF-1) [5
] which is associated with increased incidence of PC particularly high grade and advance stage disease [10
]. Additionally, coffee is considered as a major source of antioxidants and many observational studies suggested that coffee consumption lower the inflammation [28
]. There is growing evidence which suggests that inflammation play a vital role in the development of PC through the generation of proliferative inflammatory lesions [30
]. Therefore, higher consumption of coffee may have a protective role in aggressive PC by reducing the inflammatory activity in tumour.
Our findings are based on a prospective cohort study in the United Kingdom, with long follow up (median: 28
years, max. 37
years), lower losses to follow up (0.01%), adjustment for other lifestyle habits and information on Gleason grades of the diagnosed cases. Our study has some limitations. First, the Collaborative study questionnaire did not have information on family history of PC and other dietary intake history including lycopene, multivitamins, processed meat and calcium which have been linked with the risk of PC in many studies [31
]. Second, we relied on self reported coffee consumption at the time of screening which may suffer from information bias. Third, although reverse causation did not appear to explain our results, we can not rule it out as a possible source of bias. Fourth, PSA testing has remarkably influenced the incidence of PC in most Western countries including the United Kingdom, so any differences in low grade and high grade PC incidence may be because of screening differences between coffee drinkers and non-drinkers. Unfortunately, current cancer registry does not hold the information on PSA and we could not assess the screening differences between groups, which may explain the observed association. Sixth, the number of cases was small in this study, however this study had a fairly large sample compared to earlier prospective studies on coffee consumption and PC. Although grade-specific analysis was based on a smaller sub-group of cases, only one earlier study has investigated the coffee intake in relation to grade-specific PC incidence [20
]. Given that the coffee consumption was assessed at baseline and the study had a fairly long follow-up, coffee intake among participants of this cohort may have changed considerably over time during the follow-up. This may have led to measurement error however; measurement error in this study is more likely to be non-differential and may have attenuated our results rather than exaggerated the association. Finally, any misclassification in coffee intake due to differences in cup size or type of coffee might bias our results. However, such misclassification would be expected to bias our results toward the null rather than the preventive association which we observed.