Cancer cells have the troublesome habit of rewriting their own genome. While in many cases this helps the cancers to grow and escape our immune system, sometimes these edits can be useful to researchers. Finnish cancer scientists say they have identified changes in the AN07 gene that are more likely to show up in prostate cancer cells than in regular prostate cells.
Researchers investigated the risk of prostate cancer associated with different forms of ANO7 – a gene linked to prostate cancer. The team hope to use known mutations in ANO7 as a quick and accurate prostate cancer test.
In a recent European study published in the International Journal of Cancer, researchers investigated the relationship between different forms of the ANO7 gene and prostate cancer risk. ANO7 was chosen for analysis as its location within the genome is associated with prostate cancer risk, it is specifically active in the prostate gland, and low activity of the ANO7 gene is associated with high-grade and metastatic prostate cancer.
For the study, they obtained DNA from blood and tissue samples from 1,769 prostate cancer patients from Finland, Sweden, and Ireland. DNA from blood samples from 1,711 men without prostate cancer (controls) were obtained for comparison.
Of the 215 forms of the ANO7 gene found among the samples, three were chosen for further analysis based on their rarity and significant effect on the production of the ANO7 protein:
- rs148609049 (Form 1)
- rs77559646 (Form 2)
- rs181722382 (Form 3)
Form 1 was found in 2% of patient blood samples. Form 2 was found in 8% of patient blood samples and 9% of castration-resistant tumour samples. Form 3 was found in 4% of patient blood samples and 18% of castration-resistant tumour samples. None of these three forms were found among controls.
Forms 1 and 2 were more common among those with a strong family history of prostate cancer. Those with Form 1 were 76% more likely to die from prostate cancer than patients with different forms. Form 2 was found more often in patients than in controls and in aggressive prostate cancer cases more than in non-aggressive cases. Form 2 was also associated with high ANO7activity in tumours. Patients with high ANO7 activity had lower overall survival rates than those without.
The findings suggest ANO7 is a gene signifying a person’s risk of prostate cancer, with different forms influencing the likelihood of developing prostate cancer as well as the nature of the disease. Moreover, screening for the first two forms may be useful in prostate cancer diagnosis and prognosis. That is, rs148609049 may be useful for assessing overall survivability and rs77559646 for assessing the aggressiveness of the disease.
In contrast to previous studies, high, not low, ANO7 activity was associated with more aggressive prostate cancer. Further research will be required to validate these results and determine whether this is a feature of ANO7-linked prostate cancer.
This study is not without its limitations. The study population consisted solely of Caucasian Northern Europeans among whom certain forms of ANO7 may be more or less prevalent than in other populations. In assessing survival, tumour ANO7 activity, but not ANO7 activity in non-cancerous tissue, was considered.
Overall, research into ANO7 seems a promising avenue for the development of new methods for prostate cancer diagnosis.
Written by Raishard Haynes, MBS
Reference: Kaikkonen, E. et al. (2018). ANO7 is associated with aggressive prostate cancer. Int J Cancer. doi: 10.1002/ijc.31746
