medwireNews: Combining a single nucleotide polymorphism (SNP)-based genetic risk score (GRS) for prostate cancer with family history (FH) could improve the stratification of inherited risk and help personalize screening strategies, research suggests.
Many existing guidelines employ family history to determine inherited risk for prostate cancer, but the investigators say that this is “insufficient,” and instead argue: “Adding the GRS to FH creates a more complete genetic risk assessment.”
Jianfeng Xu (NorthShore University HealthSystem, Evanston, Illinois, USA) and colleagues assigned a GRS based on 110 SNPs associated with prostate cancer risk to 3225 men of European ancestry from the REDUCE trial, which assessed the chemopreventive effects of dutasteride in cancer-free men at increased risk. Twenty-one percent of the participants were classed as low risk on the basis of the GRS, while 60% had an average risk and 19% had a high risk.
There was a significant association between GRS risk groups and the diagnosis of prostate cancer over the 4-year follow-up period, such that detection rates rose from 14% for the low-risk group to 22% for the average-risk and 32% for the high-risk groups.
FH was similarly significantly associated with prostate cancer diagnosis, at rates of 21% for men with a negative FH and 27% for those with a positive FH.
And combining genetic risk and FH further improved the risk stratification. For instance, among men with a low-risk GRS, prostate cancer was detected in 13% of participants with a negative FH, but in 18% of those with a positive FH, while in the high-risk group, the rates were 31% and 37% for men with a negative and positive FH, respectively.
The findings were similar when Xu et al used the likelihood of prostate cancer disease-free survival as an outcome.
There was also a significant association between the GRS and age at prostate cancer diagnosis, whereby the average age at diagnosis was more than 80 years for men at low risk, 77 years for those at average risk, and 74 years for those at high risk.
By contrast, the average age at diagnosis for men with a negative and positive FH was 77 and 73 years, respectively.
Xu and colleagues summarize in JAMA Network Open that “[c]ombining family history and genetic risk score can better stratify inherited risk to develop personalized prostate cancer screening strategies.”
And they conclude: “Such an inherited risk stratification strategy will benefit not only men at high risk by recommending earlier and more frequent [prostate cancer] screening but also men at low risk by recommending decreased or delayed [prostate cancer] screening.”
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