Journal of the National Comprehensive Cancer Network : JNCCN · 2025
Association of HOXB13 G84E With Prostate Cancer Among 592,158 Men.
СтатьяResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Crawford Taylor B, Nelson Tyler, Karunamuni Roshan, Desai Heena, Hausler Ryan, Teerlink Craig, Carter Hannah, Pagadala Meghana S, Alba Patrick R, DuVall Scott L, Danowski Morgan E, Brunette Charles A, Ratner Dmitry, Garraway Isla P, Rose Brent S, Smith Jeffrey R, Cooney Kathleen A, Vassy Jason L, Hauger Richard L, Lynch Julie A, Seibert Tyler M, Maxwell Kara N
Аннотация
BACKGROUND: The HOXB13 c.G251G>A:p.G84E (rs138213197) variant is associated with an increased risk of prostate cancer (PrCa); however, its link to aggressive PrCa remains controversial. Limited data from large, population-based cohorts are available to inform genetic counseling and clarify the PrCa risk associated with this variant.
PATIENTS AND METHODS: We identified individuals heterozygous for HOXB13 p.G84E or homozygous wild-type among 592,158 male participants in single nucleotide polymorphism genotyping data from the Veterans Health Administration (VA) Million Veteran Program (MVP). Individuals with PrCa were identified, and Cox proportional hazards models were used to estimate age-specific risk of developing PrCa. In a subset of patients who underwent their first prostate biopsy within the VA health system, a multivariable logistic regression model-adjusting for known PrCa risk factors-was used to assess PrCa risk.
RESULTS: Of the MVP participants, 1,660 (0.3%) were heterozygous for HOXB13 p.G84E. Heterozygosity was significantly associated with risk of any PrCa (hazard ratio [HR], 3.17 [95% CI, 2.90-3.46]; P<2.0E-16), metastatic PrCa (HR, 2.99 [95% CI, 2.32-3.84]; P<2.0E-16), and PrCa-specific mortality (HR, 2.63 [95% CI, 1.66-4.19]; P=4.4E-05). In the subset of MVP participants who underwent prostate biopsy within the VA health system (n=36,321), a multivariable logistic regression model controlling for known PrCa risk factors showed that HOXB13 p.G84E heterozygotes had a higher risk of PrCa diagnosis (odds ratio, 2.60 [95% CI, 1.94-3.52]; P<.001). HOXB13 p.G84E heterozygotes were diagnosed with PrCa at a slightly younger age but had similar Gleason score distributions and comparable rates of de novo, any, and castration-resistant metastatic disease.
CONCLUSIONS: In the largest cohort of men with the HOXB13 p.G84E variant studied to date, we demonstrate a moderately increased lifetime risk of PrCa. However, the PrCa that develops is not more aggressive, although it may occur at younger ages. Further research is warranted to determine whether early PrCa screening in HOXB13 p.G84E heterozygotes improves outcomes.
PATIENTS AND METHODS: We identified individuals heterozygous for HOXB13 p.G84E or homozygous wild-type among 592,158 male participants in single nucleotide polymorphism genotyping data from the Veterans Health Administration (VA) Million Veteran Program (MVP). Individuals with PrCa were identified, and Cox proportional hazards models were used to estimate age-specific risk of developing PrCa. In a subset of patients who underwent their first prostate biopsy within the VA health system, a multivariable logistic regression model-adjusting for known PrCa risk factors-was used to assess PrCa risk.
RESULTS: Of the MVP participants, 1,660 (0.3%) were heterozygous for HOXB13 p.G84E. Heterozygosity was significantly associated with risk of any PrCa (hazard ratio [HR], 3.17 [95% CI, 2.90-3.46]; P<2.0E-16), metastatic PrCa (HR, 2.99 [95% CI, 2.32-3.84]; P<2.0E-16), and PrCa-specific mortality (HR, 2.63 [95% CI, 1.66-4.19]; P=4.4E-05). In the subset of MVP participants who underwent prostate biopsy within the VA health system (n=36,321), a multivariable logistic regression model controlling for known PrCa risk factors showed that HOXB13 p.G84E heterozygotes had a higher risk of PrCa diagnosis (odds ratio, 2.60 [95% CI, 1.94-3.52]; P<.001). HOXB13 p.G84E heterozygotes were diagnosed with PrCa at a slightly younger age but had similar Gleason score distributions and comparable rates of de novo, any, and castration-resistant metastatic disease.
CONCLUSIONS: In the largest cohort of men with the HOXB13 p.G84E variant studied to date, we demonstrate a moderately increased lifetime risk of PrCa. However, the PrCa that develops is not more aggressive, although it may occur at younger ages. Further research is warranted to determine whether early PrCa screening in HOXB13 p.G84E heterozygotes improves outcomes.