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Caffeine genotype linked to better prostate cancer survival

29th September 2022

One specific caffeine genotype in men who drink more coffee is significantly associated with a longer prostate cancer specific survival time

A caffeine genotype is associated with a longer prostate cancer specific survival among men who drink higher amounts of coffee in comparison to other genotypes, according the findings of a study by an international team of researchers.

Prostate cancer the 2nd most common cancer in men worldwide and there were more than 1.4 million new cases in 2020. One possible lifestyle factor that may have a protective role against the development of prostate cancer is intake of coffee. In fact, a 2015 meta-analysis of 13 cohort studies including 539,577 participants concluded that coffee consumption may be associated with a reduced risk of prostate cancer and it that there was also has an inverse association with non-advanced prostate cancer.

Caffeine is metabolised by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme although single nucleotide polymorphisms (SNPs) have been identified which impact on the speed with which caffeine is metabolised giving rise to differences in caffeine genotype. For example, rs762551 (also known as -164A>C or -163C>A) is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene (which metabolises caffeine).

Furthermore, rs762551 SNP can affect CYP1A2 enzyme activity and has been used to categorise individuals as either ‘fast’ (AA genotype) or ‘slow’ (AC or CC genotype) caffeine metabolisers. Moreover, there is some data to suggest that individuals with a ‘fast’ caffeine genotype with localised prostate cancer and a low to moderate coffee intake, are less likely to experience grade progression than non-consumers.

Based on this earlier work, suggesting that a caffeine genotype may affect prostate cancer survival, for the present study, researchers examined the association between coffee intake, rs762551 genotype and survival among men with prostate cancer.

Using data from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium, researchers included individuals with the caffeine genotype of interest (i.e. -163C>A rs762551). Coffee consumption before their diagnosis of prostate cancer was categorised as none/very low (0 to 3 or more cups/week); low’ (3 or more cups/week) or high (2 or more cups/day). The low consumption level was used as the reference point for statistical analysis.

Caffeine genotype and prostate cancer survival

The whole cohort comprised 5,727 men with a median age of 63 years and who consumed a median of 2.5 cups of coffee/day. Individuals were followed for a median of 5.1 years. In the overall cohort there were 906 deaths including 481 due to prostate cancer.

A high intake of coffee was associated with a 15% lower (but non-significant) reduction in prostate cancer-specific survival in the overall cohort (Hazard ratio, HR = 0.86, 95% CI 0.68 – 1.08, p = 0.19). A similar, non-significant reduction was also observed for overall survival (HR = 0.90, 95% CI 0.77 – 1.07, p = 0.24).

For men in the group with localised disease, a higher intake of coffee was associated with a significantly longer prostate cancer-specific survival (HR = 0.66, 95% CI 0.44 – 0.98, p =0.04). However, among those with more advanced disease (e.g., node positive, distant metastases), higher coffee intake was not associated with better survival (HR = 0.92, 95% CI 0.69 – 1.27, p = 0.60).

When researchers considered survival among those with different caffeine genotypes, those with the AA genotype (i.e., the fast metabolisers), there was a significantly longer prostate cancer specific survival (HR = 0.67, 95% CI 0.49 – 0.93, p = 0.017) for the highest level of coffee intake. In contrast, this relationship was non-significant for the other genotype (AA/CC) examined (HR = 1.04, 95% CI 0.74 – 1.47, p = 0.8).

The authors concluded that coffee intake was associated with longer prostate cancer specific survival among men with a CYP1A2 -163AA genotype and suggested that this finding would require further replication.

Gregg JR et al. Coffee Intake, Caffeine Metabolism Genotype, and Survival Among Men with Prostate Cancer. Eur Urol Oncol 2022

Higher coffee intake associated with reduced risk of acute kidney injury

14th June 2022

A higher coffee intake appears linked to a lower risk of acute kidney injury offering the potential for cardio-renal protection through diet

A higher intake of coffee could represent a dietary intervention to protect against the development of incident acute kidney injury (AKI) according to the findings of a prospective cohort study by US researchers.

Coffee is a widely consumed drink and in a 2017 umbrella review of health benefits, it was concluded that there was a large reduction in risk for several health conditions after consumption of three to four cups a day. Furthermore, a 2019 study, found that a higher coffee intake (> 3 cups/day) was associated with a 21% lower risk of hospitalisation for liver-related hospitalisations.

A higher coffee intake has been shown to be associated with a lower risk of type 2 diabetes which is an important precursor to chronic kidney disease. In fact, a higher intake of coffee has actually been found to be associated with a reduced risk of incident chronic kidney disease which suggests that the drink might reduce the risk of progression of kidney disease.

Nevertheless, whether or not consumption of coffee is associated with a reduced risk of incident acute kidney injury is currently uncertain and was the subject of the present study.

The US team used data collected as part of the Atherosclerosis Risk in Communities (ARIC) study, which is designed to investigate the aetiology of atherosclerosis and its clinical sequelae and variation in cardiovascular risk factors, medical care, and disease by race, sex, place and time.

The study includes over 14,000 participants aged 45 to 64 years and as part of the study, consumption of coffee was self-reported and categorised as never; almost never (< 1 cup/day), 1 cup/day, 2 to 3 cups/day and > 3 cups/day. Incident cases of acute kidney injury (AKI) were defined as requiring hospitalisation during the follow-up period.

Other participant data collected included demographics, co-morbidities including diabetes, alcohol intake and smoking status. Hazard ratios were calculated based on a comparison with those who reported never consumed coffee and models fully adjusted for covariates such as co-morbidities, age, gender etc.

Higher coffee intake and acute kidney injury

A total of 14,207 individuals with a mean age of 54.2 years (54.9% female) were included in the analysis. Overall, 27% reported never drinking coffee, 23% drank 2 to 3 cups/day and 17% reported drinking more than 3 cups/day.

During a median follow-up period of 24 years, there were 1694 incident cases of AKI and in the fully-adjusted model, comparison of never to any level of coffee intake was associated with an 11% lower risk of AKI (hazard ratio, HR = 0.89, 95% CI 0.80 – 0.99, p = 0.03).

When the researchers compared the level of coffee drunk, compared to those who never drank the beverage, consuming 2 – 3 cups/day was associated with a 17% lower risk of developing AKI (HR = 0.83, 95% CI 0.72 – 0.95) and a 12% reduced risk for those drinking more than 3 cups/day (HR = 0.88).

The authors concluded that a higher coffee intake was associated with a lower risk of incident AKI and called for larger studies to investigate the effects of coffee consumption on kidney perfusion in those with impaired kidney function at high risk for AKI.

Tommerdahl KL et al. Coffee Consumption May Mitigate the Risk for Acute Kidney Injury: Results From the Atherosclerosis Risk in Communities Study Kidney Int Rep 2022