Genetic clues link lipoprotein A to the prostate

picture: Prostate cancer
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Credit: Darryl Leja, National Human Genome Research Institute, Flickr, CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/)

A new analysis has discovered a potential link between a higher risk of prostate cancer and genetic variants associated with higher blood levels of lipoprotein A, the cholesterol transport molecule. Anna Ioannidou of Imperial College London, UK, and her colleagues present these findings in the open-access journal. OLP Medicine.

Some factors associated with a higher risk of prostate cancer cannot be changed, 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 changed. Previous research suggests that higher blood lipid levels may also be associated with increased risk. If so, lipid-lowering drugs could theoretically reduce the risk of prostate cancer. However, the existing evidence for associations between blood lipids and prostate cancer is inconclusive.

To better understand these possible associations, Ioannidou and his colleagues analyzed the links between prostate cancer risk and several blood lipids: namely lipoprotein A, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and apolipoproteins A and B. They relied on two major research initiatives, UK Biobank and the PRACTICAL consortium, to analyze prostate cancer risk and genomic data for hundreds of thousands of people.

The study used a method known as Mendelian randomization, which exploits the randomness inherent in the genetic process of meiosis to bolster the validity of an analysis. So, instead of considering direct measurements of lipids in the bloodstream, the researchers assessed variations in individuals’ DNA sequences that are associated with different blood lipid levels. Next, they analyzed whether these genetic variants were statistically linked to prostate cancer risk.

The analysis showed that genetic variants that predict higher blood levels of lipoprotein A were associated with a higher overall risk of prostate cancer, as well as a higher risk of advanced or early prostate cancer. The researchers found no significant association for any of the other blood lipids.

These results suggest the possibility that drugs that lower lipoprotein A could be developed or repurposed to reduce the risk of prostate cancer in some people. Further research will be needed to confirm the associations observed in this study and to clarify the underlying biological mechanisms.

The authors add: “Our study suggests that people with higher blood levels of lipoprotein A, which is a protein that carries cholesterol in the blood, may have a greater risk of developing prostate cancer.”

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In your coverage, please use this URL to provide access to the article available for free in OLP Medicine:

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003859

Quote: Ioannidou A, Watts EL, Perez-Cornago A, Platz EA, Mills IG, Key TJ, et al. (2022) The relationship between lipoprotein A and other lipids with prostate cancer risk: a multivariable Mendelian randomization study. PLoS Med 19(1): e1003859. https://doi.org/10.1371/journal.pmed.1003859

Author countries: United Kingdom, United States, Norway

Funding: KKT was supported by Cancer Research UK (C18281/A29019). ELW was supported by the NDPH Early Career Fellowship. APC is supported by a Population Research Fellowship from Cancer Research UK (C60192/A28516) and the World Cancer Research Fund (WCRF UK), under the Word Cancer Research Fund International Grants Program (2019 /1953). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


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