Genetic Clues Link Lipoprotein A to Prostate Cancer Risk

Some factors associated with higher risk of prostate cancer (PCa) cannot be modified, such as older age and being of African descent. Meanwhile, other risk factors for the aggressive form of the disease, such as smoking and obesity, can potentially be modified.

Lipid-lowering therapies are cheap and well established for lowering cardiovascular risk. Yet, there is no conclusive evidence that repurposed lipid-lowering drugs are effective for the prevention of PCa. It is therefore important to determine whether blood lipids increase PCa risk, especially lethal disease,

Image: Histopathology of adenocarcinoma of the prostate on needle biopsy consisting of small glands with amphophilic cytoplasm (Photo courtesy of Professor Jonathan I. Epstein, MD)

An international team that included Cancer Epidemiologists and led by those at the Imperial College London (London, UK) analyzed links between prostate cancer risk and several blood lipids: namely, lipoprotein A (Lp(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoproteins A and B.

The study employed a method known as Mendelian randomization, which harnesses the inherent randomness of the genetic process of meiosis to boost the validity of an analysis. So, instead of considering direct measurements of lipids in the bloodstream, the team evaluated variations in individuals’ DNA sequences that are associated with different blood levels of the lipids. Then, they analyzed if these genetic variants were statistically linked to prostate cancer risk.

The investigators reported that their analysis showed that genetic variants that predict higher blood levels of lipoprotein A were associated with a higher overall risk of prostate cancer, and also a higher risk of advanced or early-age-onset prostate cancer. They did not find any significant associations for any of the other blood lipids. These findings suggest the possibility that lipoprotein A-lowering drugs could be developed or repurposed to lower risk of prostate cancer for some individuals.

The authors concluded that their findings from this study point towards a positive association between genetically predicted Lp(a) concentrations and risk of total, advanced, and early age onset PCa. Screening for high Lp(a) concentrations could possibly be investigated in the future to identify high-risk groups for PCa. Given that Lp(a) concentrations depend significantly on genetics, modification of Lp(a) levels may be achieved by developing Lp(a)-lowering drugs that might be on the horizon. The study was published on January 27, 2022 in the journal PLOS Medicine.

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Imperial College London