Analysis of the frequency of mutations in genes associated with prostate cancer

Keywords

prostate cancer - genetic mutations - variants impact

Introduction: Prostate cancer (PC) is the second most commonly diagnosed cancer in the male population worldwide, a disease with slow and silent progression that occurs most often in the middle or late stages of life. In addition, it is a disease linked to genetic factors, as studies show that 10 to 12% of cases are associated with hereditary genetic mutations and epigenetics, which favor the growth and survival of tumor cells.

Objective: To identify the genetic mutations most frequently associated with prostate cancer.

Methodology: The search was conducted using the National Cancer Institute Genomic Data Commons (GDC) database, analyzing information related to the frequency of genetic mutations in 555 cases of prostate cancer. The VEP impact variants were classified as High, Low, Moderate or Modified, according to the gene evaluated. Through PolyPhen Impact, the possible impact resulting from alterations in gene structure was classified as Benign, Possibly Damaging, or Probably Damaging. Subsequently, a more specific search was performed for the 3 genes with the highest number of variants with significant impact, identifying the cancer typology and its statistics regarding the age of diagnosis.

Results: 22 genes were evaluated, and of these 555 cases, there were 490 modifications. In this scenario, 3 genes had the highest number of variants with significant impact. The TP53 gene (n = 71, 12.9%) was associated with an average age at diagnosis of 60.75 years. In 25 cases, the variants, according to the VEP, had a high impact, 46 cases had moderate impact and only 14 cases were considered benign regarding the PolyPhen impact. The SPOP (n = 61, 11%) had an average age of onset of around 63 years. Thus, with 2 cases of high impact and 59 cases of moderate impact and 40 cases classified as benign. Finally, the FOXA1 gene (n = 39, 7%) was identified on average at 63.2 years of age, with 7 cases considered high impact and 29 cases as moderate.

Conclusion: The frequency of genetic alterations occurring among the cases evaluated was high, especially in the TP53, SPOP and FOXA1 genes. Therefore, it is important to track the presence of these mutations, so that the carriers can undergo individualized and preventive monitoring to minimize the risks of developing the disease.

Corresponding author: Giulia Di Credico Paranhos (e-mail: [e-mail]).