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Letter to the Editor: “Association between metformin medication, genetic variation and prostate cancer risk”—genotyping and patient categorizations, do they matter?

Prostate Cancer and Prostatic Diseases volume 24, pages 278–279 (2021)Cite this article

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We read with interest the research article titled, “Association between metformin medication, genetic variation and prostate cancer risk” [1], published in your esteemed Prostate Cancer and Prostatic Diseases journal. We would like to put forth two burning queries, one about the single nucleotide polymorphisms (SNPs) included under study and other about the groupings of patient cohorts.

In the present study, the authors have analyzed 27 SNPs and also have executed a genome-wide association study (GWAS)—which are commendable jobs. However, the glaring deficiency is the non-inclusion of the SNPs related to the organic cation/ carnitine transporter 1 (OCTN1) [SLC22A4]. OCTN1 transporters are expressed on the apical (mucosal) membrane of the enterocytes, thereby, helping in the absorption of metformin. Multiple in vitro studies [2, 3] have delineated the significance of these transporters in the intestinal absorption of metformin. Further, a large meta-analysis [4], conducted under the auspices of the Metformin Genetics (MetGen) Consortium, comprising nearly 8000 individuals across 10 international cohorts on metformin therapy evaluated nine SNPs in the genes coding for five different transporter genes—including that of OCTN1. The SNPs rs272893 (T306I) and rs1050152 (L503F) of OCTN1 were studied in the patient populations of European (Caucasian) ancestry and in the present study [1], nearly 3/4th of the population were of the same origins. The thiamine transporter 2 (THTR-2; SLC19A3) and the serotonin reuptake transporter (SERT; SLC6A4) are also found to play definitive roles in the intestinal absorption of metformin [5]. More importantly, corroborative evidences are accumulating with regards to key involvement of the intestinal system in the pharmacodynamic effect of metformin [6]—the same can hold true with respect to plausible effects of metformin on prostate cancer [7]. Recently, through a semi-mechanistic model [8], it was divulged that the variability in metformin PK could be more explained by investigating the absorption processes than the elimination processes; this result and the other above discussions underpin the importance of studying the intestinal transporters of metformin particularly that of OCTN1.

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Authors and Affiliations

  1. Department of Pharmacology, Sri Venkateshwaraa Medical College Hospital and Research Centre (SVMCH & RC), Puducherry, India

    Gerard Marshall Raj

  2. Department of Urology, Velammal Medical College Hospital & Research Institute, Madurai, India

    Rama Krishnan

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Correspondence to Gerard Marshall Raj.

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Raj, G.M., Krishnan, R. Letter to the Editor: “Association between metformin medication, genetic variation and prostate cancer risk”—genotyping and patient categorizations, do they matter?. Prostate Cancer Prostatic Dis 24, 278–279 (2021). https://doi.org/10.1038/s41391-020-00269-1

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