New gene links to mHSPC

[Derf4223]

Article from cancertherapyadvisor.com

Genes Linked to Aggressive Prostate Cancer

Researchers say they have identified genes that should be considered for gene panel testing in prostate cancer.

The researchers found evidence to suggest that variants in BRCA2, ATM, NBN, MSH2, XRCC2, and MRE11A are associated with aggressive prostate cancer. These findings were published in JAMA Oncology.

For this study, researchers performed 2-stage exome sequencing on 17,546 men of European ancestry from 18 international studies. The cohort included 8361 patients with nonaggressive prostate cancer and 9185 patients with aggressive prostate cancer (including 2397 with metastatic disease).

The researchers conducted exome-wide sequencing and focused sequencing on 29 DNA repair pathway and cancer susceptibility genes, many of which are included in gene panels.

The researchers found the strongest evidence to suggest that variants in BRCA2, ATM, and NBN are associated with an increased risk of aggressive prostate cancer.

The frequency of deleterious BRCA2 alleles was 0.7% in patients with nonaggressive disease, 2.4% in patients with aggressive disease (odds ratio [OR], 4.29; 95% CI, 3.15-5.86; P =4.0 × 10−20), and 3.0% in patients with metastatic disease (OR, 5.61; 95% CI, 3.73-8.44; P =1.3 × 10−16).

The frequency of deleterious ATM alleles was 0.7% in patients with nonaggressive disease, 1.6% in patients with aggressive disease (OR, 2.17; 95% CI, 1.58-2.99; P =1.6 × 10−6), and 1.9% in patients with metastatic disease (OR, 2.80; 95% CI, 1.83-4.29; P =1.9 × 10−6).

The frequency of deleterious NBN alleles was 0.2% in patients with nonaggressive disease and 0.5% in patients with metastatic disease (OR, 5.16; 95% CI, 2.19-12.12; P =1.7 × 10−4).

The researchers found nominal evidence to suggest associations between aggressive prostate cancer and variants in MSH2 (OR, 3.27; 95% CI, 1.29-8.31; P =.01) and XRCC2 (OR, 6.24; 95% CI, 1.24-31.4; P =.03). The team also found a nominal association between variants in MRE11A and metastatic prostate cancer (OR, 4.70; 95% CI, 1.39-15.90; P =.01).

There was evidence to suggest potential associations between aggressive disease and variants in 5 additional genes — TP53, RAD51D, BARD1, GEN1, and SLX4 — but these associations did not reach statistical significance.

“The findings of this genetic association study implicate genes to be considered for gene panel testing in PCa [prostate cancer] that would be beneficial to a broad group of men, including those diagnosed at any stage of the disease,” the researchers wrote. “Additional large-scale sequencing studies, particularly in diverse populations, are needed to confirm the involvement or lack thereof of the genes lacking strong statistical evidence reported here.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Darst BF, Saunders E, Dadaev T, et al. Germline sequencing analysis to inform clinical gene panel testing for aggressive prostate cancer. JAMA Oncol. Published online September 21, 2023. doi:10.1001/jamaoncol.2023.3482

[j-o-h-n]

From another member's post, dated 16 days ago.

Warriors,

Diagnosed w MHSPC May 2021. Gleason 5+4 . PSA 780.

Started ADT right away . Went through 2021 and 2022 H2 body adjusting to all the changes. 2023 H1 pretty solid , feeling pretty good. Recent PSA went from 0.32 to 0.64. CT unchanged but bone scan w contrast shows new uptake. RO recommending Xofigo.

Can you please share your experience on this treatment and whether you modified your ADT during the 20 weeks ? Did you have any side effects? What was the outcome +12 mos?Thanks gents and keep up the fight !!!💪

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 09/29/2023 3:23 PM DST

[j-o-h-n]

Reply to Derf4223

Metastatic hormone-sensitive prostate cancer (mHSPC) is when cancer has spread past the prostate into the body, but it can be treated with hormone therapy. This means that male sex hormones, including androgens like testosterone, can be blocked or stopped to slow cancer growth.

Abbreviations, Abbreviations They're killing me, like Prostate Cancer is.

Guy ends up at the Pearly Gates and has only one guess to enter, for eternity...

Gate 1 labeled ELS

Gate 2 labeled VLH

Here's a Hint: ____________

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 09/29/2023 4:01 PM DST