Gene variant associated with increased risk of BPH

A genetic polymorphism in the PTGS2 gene was found to be associated with an increased risk of benign prostatic hyperplasia (BPH), according to recent data published in Oncotarget.^1,2

The investigators found no link between the PTSG1 gene and either prostatic disease.

Specifically, the investigators found a significant association between the C allele of the single nucleotide polymorphism (SNP)-765G>C of the PTGS2 gene and an increased risk of BPH in Lebanese men (OR, 2.30; P = .01). The C allele was also significantly more common among patients who had both BPH and prostate cancer compared with patients who had no prostatic disease (OR. 1.59; P = .07).

Data also showed a potential association between the C allele and prostate cancer (P < .1).

“To our knowledge, this is the first study to report a strong association between the C allele of the SNP -765 G>C of the PTGS2 gene and an increased risk of BPH among Lebanese men,” the authors wrote. “Our data also suggest that the C allele of this SNP is likely associated with an increased risk of [prostate cancer]. This finding supports and extends previously reported findings on the association of this polymorphic allele with an increased risk of [prostate cancer] in other ethnic groups and various other cancers.”

For the study, the investigators collected blood leucocyte DNA from 168 individuals, including 61 participants with confirmed prostate cancer, 51 participants with confirmed BPH, and 56 participants with no prostatic disease. Prostate health was determined by serum total prostate-specific antigen (PSA) levels followed by a digital rectal exam as necessary. Patients with a serum total PSA level between 4 ng/mL and 10 ng/mL also received a free PSA test. The ratio between free and total PSA was then used to differentiate BPH and prostate cancer.

Patients’ DNA samples were genotyped using the PCR-RFLP method. The investigators specifically focused on 2 common gene variants: SNP-842A>G (rs10306114) of the PTGS1 gene and SNP-765G>C (rs20417) of the PTGS2 gene.

The investigators found no link between the PTSG1 gene and either prostatic disease.

Specifically, they wrote, “No significant association was observed between the A or G alleles or the AA, AG, or GG genotypes of the SNP-842A>G of the PTGS1 gene and prostatic diseases.”

However, according to the authors, the findings on the link between certain genotypes of the SNP -765 G>C of the PTGS2 geneand BPH is significant, and may indicate a potential benefit of COX-2 inhibitors in certain patients.

“Based on these observations, it is plausible to suggest the prophylactic use of COX-2 inhibitors for elderly individuals with PTGS2 genotypes associated with an increased risk of proliferative prostatic diseases,” they wrote.

However, they also acknowledge several limitations of their current analysis.

“It is an association study rather than a functional one, which means it does not explore the underlying mechanisms,” they explained. “In addition, the study’s small sample size of a single ethnic group presents challenges. These limitations were difficult to address due to the lack of clinical samples beyond leftover blood DNA, Lebanon’s small population, and the limited pool of older men willing to participate in genetic studies.”

REFERENCES

1. Sheehan BJ, Edwards B, Soto Medrano I, et al. Association between two single nucleotide polymorphisms of the Prostaglandin-Endoperoxide Synthase 1 and 2 genes and cell proliferative prostatic diseases in Lebanon. Oncotarget. 2025 Apr 4:16:262-272. doi:10.18632/oncotarget.28710

2. Gene variant linked to benign prostate hyperplasia risk in Lebanese men. News release. Impact Journals LLC. April 15, 2025. Accessed April 16, 2025. https://www.eurekalert.org/news-releases/1080506