International Journal of Clinical Case Reports 2024, Vol.14, No.4, 202-209 http://medscipublisher.com/index.php/ijccr 205 Population-based studies have established that G84E can stratify high-risk individuals for earlier screening and more intensive monitoring (Kote-Jarai et al., 2015). This variant's role in early diagnosis is especially significant in populations of European descent, where it has been linked to a greater likelihood of hereditary prostate cancer. 4.2 Significance of HOXB13 gene variants in prostate cancer risk assessment HOXB13 gene mutations, particularly G84E, are associated with a marked increase in prostate cancer risk. The G84Emutation contributes to a 3-fold higher risk of developing the disease compared to non-carriers (Maia et al., 2015). Studies show that this variant is particularly valuable for assessing risk in individuals with a family history of prostate cancer, where the odds ratio can be even higher (Figure 2) (Dupont et al., 2021). Moreover, risk assessment models incorporating HOXB13 variants alongside other genetic markers such as BRCA2 and ATM have proven effective in identifying individuals at higher risk for aggressive prostate cancer (Sipeky et al., 2018). Figure 2 Association of genetic variants of the HOXB locus with prostate cancer in combined ICPCG, NFPCS and PLCO subjects (Adopted from Dupont et al., 2021). 4.3 Potential application of HOXB13 gene variants in personalized treatment HOXB13 mutations have potential applications in guiding personalized treatment strategies for prostate cancer. As HOXB13 interacts with androgen receptor (AR) signaling, the presence of specific variants may indicate susceptibility to certain therapies, such as androgen deprivation therapy (ADT) or AR-targeted treatments (Park et al., 2019). Recent studies have highlighted that the expression of HOXB13 may modulate the efficacy of therapies targeting AR, thus influencing treatment outcomes in advanced and castration-resistant prostate cancer (Patel et al., 2023). Understanding these variants' role in treatment response allows for the development of more tailored therapies that address the molecular mechanisms driving individual tumors (Johng et al., 2016). 4.4 Role in predicting prostate cancer recurrence and prognosis HOXB13 overexpression has been shown to predict early prostate-specific antigen (PSA) recurrence following radical prostatectomy. Patients exhibiting high levels of HOXB13 expression have poorer outcomes, as this variant is linked to more aggressive disease and higher Gleason scores. HOXB13 variants, in combination with AR and PSA levels, provide strong prognostic information about recurrence and overall survival after treatment (Zabalza et al., 2015). Further studies have demonstrated that HOXB13 can be used as a marker for identifying patients at higher risk of biochemical recurrence, particularly when combined with other genetic markers like CIP2A(Sipeky et al., 2018). 5HOXB13 Gene Variants as Therapeutic Targets 5.1 Targeted therapy strategies based onHOXB13 variants HOXB13 is a critical player in androgen receptor (AR) signaling, and therapies targeting HOXB13's interaction with AR and its variants are showing promise. HOXB13 is essential for the regulation of AR splice variant-7
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