Researchers from the University of North Texas have identified a new genetic mutation in the ALKBH7 gene that is associated with prostate cancer, particularly in African-American men.
The findings suggest that this ALKBH7 mutation could not only be used as a biomarker to diagnose prostate cancer, but that therapies targeting this mutation may help such patients.
The study, “ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding,” recently appeared in PLOS Computational Biology.
When the control mechanisms that detect and repair DNA damages fail, irreversible genetic mutations that lead to cancer can rise may occur. Understanding which mutations are involved in the onset and progression of each patient’s tumor could bring about better personalized anti-cancer therapies.
Alice Walker and her colleagues at UNT focused on the occurrence of cancer-related mutations in the ALKBH family of genes in prostate cancer.
The nine genes in the ALKBH group code for enzymes responsible for correcting genetic mistakes that occur during DNA replication. Alterations in the levels of some of these family members are associated with different cancer types, including bladder, lung, rectal and prostate cancer.
Using the HyDn-SNP-S software program, Walker’s team examined the genetic material of a cohort (phs000207.v1.p1) of 1,172 men with prostate cancer and 1157 controls of European descent. This approach allowed them to specifically compare the DNA sequence of ALKBH gene family members in controls versus prostate cancer cases. They identified one genetic mutation in the ALKBH7 enzyme that was significantly associated with prostate cancer.
To further confirm this association, the authors used a second set of prostate cancer data (phs000306), which included 1423 black men and 1,373 controls. They observed the same link between the mutation and prostate cancer in this second data set.
Importantly, the team found that black men who had the mutant version of the ALKBH7 enzyme had a 45 percent increased risk of developing prostate cancer compared to African-American men with a functioning enzyme.
A careful examination by computer simulations and laboratory tests showed that the mutation led to a structural change in the enzyme that significantly decreased its ability to perform its normal DNA repair activity.
“Scanning the DNA of individuals in the target population for this mutation could help indicate those with a higher risk of developing prostate cancer before symptoms are evident,” Walker said in a press release, adding that further studies are still needed to learn the mechanisms through which this mutation leads to prostate cancer development.
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