The Hype and Promise of the Polygenic Risk Score (PRS)

Persis, a friend, is of Parsi (Zoroastrian) origin, a community in India that has a higher risk of breast cancer than the general population [1]. Her mother had breast cancer and so did one aunt. She got herself tested for BRCA1 and BRCA2 gene mutations that carry a high risk (50-87%) of developing breast as well as ovarian cancer [2]. Ms. Angelina Jolie has a similar family history of breast cancer and BRCA1 and BRCA2 mutations, for which she had a double mastectomy done, followed 2 years later by oophorectomy (removal of the ovaries), to reduce her risk of breast and ovarian cancer. She explained these decisions of hers in a New York Times opinion piece.

Unlike the Mendelian inherited genetic diseases like thalassemia that I wrote about some time ago, where the presence of one copy (dominant) or two copies (recessive) of the abnormal gene, will always cause the disease to occur, in these “genomic” situations, there is a “risk”, which may either be absolute or relative and may in turn manifest with disease or not. It is likely that Persis would never have landed up with breast cancer, but with a greater than 50% absolute risk, she took an informed decision in conjunction with a geneticist and other experts in breast cancer and then opted to have a double mastectomy.

Genomics  therefore, as against “genetics” “is the study not just of single genes but the functions and interactions of all the genes in the genome.” [3]

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