Genetic basis of inflammatory response in prostate cancer health disparity
Cancer Genetics and Therapeutics
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Primary Categories:
- Clinical-Adult
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Secondary Categories:
- Clinical-Adult & Pediatric
Introduction:
Extensive research has explored the link between inflammation and cancer, with recent emphasis on its role in tumor formation and progression. Inflammation can either promote or suppress cancer development. There's currently a shift towards utilizing inflammatory response genes (IRGs) for a more comprehensive understanding rather than the serum markers. This approach unveils deeper insights into inflammation's role in cancer and potential interventions. Prostate cancer (PCa), notably more aggressive and lethal in individuals of African ancestry, poses a significant burden on healthcare systems. Inflammation contributes to PCa progression through various mechanisms, yet there's limited analysis of IRGs' role in different malignancies, and research on somatic variants, particularly addressing health disparities, remains insufficient.
Methods:
PCa patients from South Africa and Australia (n=117 and 53 respectively) were enrolled and after sample collection, deep sequencing was conducted to generate whole-genome data. The GSEA (Gene set Enrichment Analysis) has compiled a list of 200 genes known as inflammatory genes which serves as a valuable resource for investigating the involvement of inflammation in diseases. We have annotated the somatic variants in IRGs including single nucleotide variants, insertion/deletions and copy number variants, and using several bioinformatic tools (i.e. SIFT, Polyphen, CGI, DrGap), the damaging potential of each variant was evaluated.
Results:
Our results showed the highest mutational recurrence in novel genes including KIF1B, C3AR1, CX2CL1, IFNGR2 suggesting them to be among the African-specific drivers for PCa. Other African deleterious somatic variants were found in LDLR, MET, OSMR and ATP2B1 genes.
Conclusion:
In conclusion, numerous somatic alterations in IRGs drive PCa tumorigenesis, however, the pattern of the altered genes involved in African patients seemed different from that of their European counterparts. Further studies are needed to evaluate the utility of IRGs as an index for measuring inflammation in cancer and to determine how effectively they can explain health disparities in PCa.
Extensive research has explored the link between inflammation and cancer, with recent emphasis on its role in tumor formation and progression. Inflammation can either promote or suppress cancer development. There's currently a shift towards utilizing inflammatory response genes (IRGs) for a more comprehensive understanding rather than the serum markers. This approach unveils deeper insights into inflammation's role in cancer and potential interventions. Prostate cancer (PCa), notably more aggressive and lethal in individuals of African ancestry, poses a significant burden on healthcare systems. Inflammation contributes to PCa progression through various mechanisms, yet there's limited analysis of IRGs' role in different malignancies, and research on somatic variants, particularly addressing health disparities, remains insufficient.
Methods:
PCa patients from South Africa and Australia (n=117 and 53 respectively) were enrolled and after sample collection, deep sequencing was conducted to generate whole-genome data. The GSEA (Gene set Enrichment Analysis) has compiled a list of 200 genes known as inflammatory genes which serves as a valuable resource for investigating the involvement of inflammation in diseases. We have annotated the somatic variants in IRGs including single nucleotide variants, insertion/deletions and copy number variants, and using several bioinformatic tools (i.e. SIFT, Polyphen, CGI, DrGap), the damaging potential of each variant was evaluated.
Results:
Our results showed the highest mutational recurrence in novel genes including KIF1B, C3AR1, CX2CL1, IFNGR2 suggesting them to be among the African-specific drivers for PCa. Other African deleterious somatic variants were found in LDLR, MET, OSMR and ATP2B1 genes.
Conclusion:
In conclusion, numerous somatic alterations in IRGs drive PCa tumorigenesis, however, the pattern of the altered genes involved in African patients seemed different from that of their European counterparts. Further studies are needed to evaluate the utility of IRGs as an index for measuring inflammation in cancer and to determine how effectively they can explain health disparities in PCa.