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Genetic risk score could improve triage of men with suspected prostate cancer

19th August 2022

A higher genetic risk score in symptomatic men is significantly associated with the development of prostate cancer over the next 2 years

Use of a genetic risk score (GRS) in men with symptoms suggestive of prostate cancer could enable the identification of those at risk and fast track them for further investigation according to the results of a study by UK researchers using a cohort from the UK Biobank database.

Prostate cancer was responsible for 1.4 million global cases in 2020 and is the 2nd most commonly occurring cancer in men. Screening for the cancer may help to save lives and a European study which followed-up on men for 13 years found that one prostate cancer death was averted per 781 men invited for screening although the authors concluded that ‘despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening.’ Symptoms potentially suggestive of prostate cancer include lower urinary tract symptoms (LUTS) including nocturia, urinary frequency or poor stream but these are often present at the time of a prostate cancer diagnosis. The use of prostate-specific antigen (PSA) in men with LUTS is another means of screening though a 2022 systematic review concluded that the available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. Prostate cancer is a highly heritable disease and there are 269 known genetic risk variants such that the use of a genetic risk score offers an approach for personalised risk prediction. Moreover, it has been suggested that the use of a GRS provides additional information to improve upon current practices in prostate cancer screening by risk-stratifying patients before initial prostate-specific antigen testing. However, to date, GRS is not routinely used and for the present study, researchers set out to assess whether a GRS was able to predict a new diagnosis of prostate cancer in men with LUTS over the next 2 years.

The team used information held in the UK Biobank and included men with LUTS but no recorded diagnosis of prostate cancer and a GRS was calculated for each participant based on the known genetic variants. The association between the GRS and prostate cancer diagnosis within 2 years of symptom onset was calculated using logistic regression and GRS scores were split into quintiles for analysis.

Genetic risk score and prostate cancer

A total of 6777 men with prostate cancer symptoms were included and of whom, 247 men had a record of prostate cancer within 2 years. For the remaining 6530 men, 62 died during the 2-year follow-up period, leaving 6448 as control patients.

Among men with symptoms, the GRS was associated with the development of symptoms over the next 2-years (odds ratio, OR = 2.12, 95% CI 1.86 – 2.41). The risk of prostate cancer was also age dependent such that men in the highest GRS quintile had a 13% greater incidence than those in the lowest (2.3%).

When researchers added age to the GRS score, the predictive power of the model improved with an area under (AUC) the receiver operating characteristic curve of 0.77 (95% CI 0.74 – 0.80) which was higher than either the GRS (AUC = 0.70) or age (AUC = 0.68) alone.

The authors discussed how the results of the study could be used to enable identification of men at low risk of prostate cancer and therefore avoid further testing but also to fast track those with the highest risk. A recognised limitation of the study was that genetic sequencing is not currently available in the UK so that the GRS approach cannot be implemented at present.

Citation
Green HD et al. Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank Br J Cancer 2022