Genetic Risk Score Associated with Patient Age at Prostate Cancer Diagnosis

A genetic risk score (GRS) is significantly associated with patient age at prostate cancer diagnosis, independent of family history, according to a study published in JAMA Network Open.¹

This research indicated that combining family history and GRS may better stratify inherited risk than family history alone for developing personalized prostate cancer screening strategies. 

“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 authors wrote. 

To calculate the GRS, researchers used an odds ratio (OR)-weighted and population-standardized score derived from well-established prostate cancer risk associated single-nucleotide polymorphisms (SNPs). In this cohort of 3,225 men, 683 (21%) were classified as low risk, 1,937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. Comparatively, 2,789 (86%) were classified as low or average risk and 436 (15$) as high risk based on family history alone. 

Men in higher GRS risk groups had a prostate cancer diagnosis-free survival rate that was worse than those in the lower GRS risk group (c² = 45.5; P < .001 for trend). Combining GRS and family history further stratified overall genetic risk, suggesting that 957 men (30% were at high genetic risk (either high GRS or positive family history), 1,667 men (52%) were at average genetic risk (average GRS and negative family history), and 601 men (19%) were at low genetic risk (low GRS and negative family history).

The median prostate cancer diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to >80 years) for men at average genetic risk, and more than 80 years (95% CI, >80 to >80 years) for men at low genetic risk. In contrast, the median prostate cancer diagnosis-free survival was 73 years (95% Ci, 71-76 years) for men with a positive family history and 77 years (95% CI, 76-79 years) for men with a negative family history. 

Additionally, the researchers noted that family history is an indirect measurement of risk based solely on family members sharing only limited genetic information. Moreover, a thorough family history can be challenging to obtain owing to age, family communication, and marital status of male relatives. Family history is also unsatisfactory to identify individuals with higher inherited risk and will miss more than 50% of high-risk men in the population. Therefore, adding the GRS to family history constructs a more complete genetic risk assessment. 

“Furthermore, as a germline marker, the GRS always precedes any phenotypes (regardless of the study design, retrospective or prospective) and therefore avoids temporal ambiguity,” the authors wrote. “However, caution should be exercised when interpreting the estimates of prostate cancer-free survival at the age of 75 years because a substantial proportion of censored patients (2,223 of 3,225 [69%]) were censored prior to the age of 75 years without a prostate cancer diagnosis.”

This research not only provides a critical piece of evidence for determining the association of age with prostate cancer risk according to the authors, but also aids in the determination of what the patient age should be for prostate-specific antigen (PSA) screening. 

According to the American Society of Clinical Oncology, prostate is the most common cancer among men outside of skin cancer. Last year, it was estimated that 174,650 men in the US would be diagnosed with prostate cancer.²

References:

1. Na R, Labbate C, Yu H, et al. Single-Nucleotide Polymorphism-Based Genetic Risk Score and Patient Age at Prostate Cancer Diagnosis. JAMA Network Open. doi:10.1001/jamanetworkopen.2019.18145.

2. ASCO. Prostate Cancer: Statistics. ASCO website. Published November 2019. cancer.net/cancer-types/prostate-cancer/statistics. Accessed January 20, 2020.