The prostate-specific (anoctamin 7) ANO7 gene may be a key player in the development of aggressive prostate cancer, found a new European study published in the International Journal of Cancer. By elevating the expression of ANO7, a potential prostate cancer susceptibility gene, it may be possible to predict disease severity and outcome, according to the researchers.
“We have hypothesized for a long time that, at the molecular level, there's probably a continuum of diseases that we now call prostate cancer. Prostate cancer has a wide spectrum of clinical behavior that ranges from decades of indolence to rapid metastatic progression and lethality. The biggest treatment challenge is determination of aggressive cancers already in early phases of the disease,” said study investigator Johanna Schleutker, PhD, professor of medical genetics, Institute of Biomedicine, University of Turku/Division of Laboratory, Turku University Hospital, Turku, Finland.
Schleutker and her colleagues sequenced ANO7 in castration-resistant tumors together with samples from unselected prostate cancer patients and unaffected men. The team uncovered two pathogenic variants which were then genotyped in 1,769 men with prostate cancer and 1,711 men without prostate cancer. Different databases along with Swedish and Norwegian cohors were used to help validate the findings.
Variant rs77559646 was associated with increased risk (OR 1.40; 95% CI, 1.09-1.78; P = .009) and with aggressive prostate cancer (Genotype test, P = .04). In addition, rs148609049 was not associated with prostate cancer risk, but was related to shorter survival (HR, 1.56; 95% CI, 1.03-2.36). Overall, high ANO7 expression was independently linked to poor survival (HR, 18.4; 95% CI, 1.43-237).
Currently, there is no clear way to diagnose aggressive prostate cancer at an early stage. However, genetic mutations such as those revealed in this study could lead to the development of accurate diagnostic tests. “Obviously, more research is needed to understand the mechanisms behind our findings. However, it is very likely that genomics will become an important tool for decision-making in prostate cancer treatment,” Schleutker told Cancer Network. Genetic testing for ANO7 could provide new opportunities for precision oncology in prostate cancer, she added.
The researchers noted that although this study involved a large population, it is limited by the fact that it primarily consists of Caucasians from Northern Europe. Further research involving other demographics is warranted to validate the findings, they noted.
William Catalona, MD, a professor of urology at Northwestern Medicine Feinberg School of Medicine, Chicago, said this study and others are providing an increased understanding of the genomics of prostate cancer. For instance, germline variants associated with deficiencies of DNA repair have been shown to increase the susceptibility to prostate cancer and its aggressiveness.
“This information has helped define distinct genomic pathways with different clinical outcomes [that] respond to different treatments,” Catalona told Cancer Network. “This excellent study performed by a highly-respected, experienced research team has identified a relatively rare genetic variant that could be inexpensively genotyped as part of a biomarker panel that, along with other parameters, could help distinguish men with aggressive prostate cancer. The authors’ caveat about validation in non-northern European white populations is important,” he confirmed.