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Caffeine genotype linked to better prostate cancer survival

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