Family History, Genetic Risk Score Combined Improves Prostate Cancer Screening

January 5, 2020

Researchers found that combining family history and genetic risk scores to determine inherited risk for prostate cancer could personalize screening strategies for men.

A recent study found that combining family history and genetic risk score in men can better stratify their inherited risk for prostate cancer to determine a more personalized screening strategy.

“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,” the researchers wrote in the study, published in JAMA Network Open.

Single nucleotide polymorphisms, the most common type of genetic variation among people, that are associated with prostate cancer risk have been identified over the years. With polygenic risk score methods, researchers have been able to demonstrate a correlation between single nucleotide polymorphisms and prostate cancer risk using genetic risk scores.

However, the researchers pointed out there is little known about how age at prostate cancer diagnosis can be associated with these genetic scores. “(Age at prostate cancer diagnosis is) a critical piece of evidence that will not only strengthen (researchers’) association with (prostate cancer) risk but, more importantly, provide direct evidence for their use in determining patient age for PSA screening.”

Therefore, the researchers aimed to evaluate the association between genetic risk score and patient age at diagnosis, as well as to compare the genetic risk score with family history risk stratification. To do so, they performed a secondary analysis of the four-year, randomized, double-blind, placebo-controlled, multicenter Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial.

The researchers performed a well-established, population-standardized genetic risk score for each participant based on 110 known prostate cancer risk-associated single nucleotide polymorphisms. Men were then stratified into low-, average- or high-risk groups.

Of the 3,225 men who were a median age of 63 years, 683 (21%) were classified as low risk, 1,937 (60%) as average risk and 605 (19%) as high risk based on genetic risk score alone, compared with 2,789 (86%) classified as low or average risk and 436 (14%) as high risk based on family history alone.

When the researchers combined genetic risk score and family history for overall genetic risk, 957 men (30%) were at high genetic risk, 1,667 men (52%) were at average genetic risk and 601 men (19%) were at low genetic risk.

The median diagnosis-free survival was 74 years for men at high genetic risk, 77 years for men at average genetic risk, and more than 80 years for men at low genetic risk.

“We found that higher (genetic risk scores) were significantly associated with an earlier age at (prostate cancer) diagnosis,” researchers wrote. “Furthermore, the association of (genetic risk score) with patient age at (prostate cancer) diagnosis was independent of (family history). As a result, a combination of (genetic risk score) and (family history) offers a more informative tool for risk stratification than does (family history) alone, the current standard of care in the assessment of inherited risk.”


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