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Page 2 of 5 Padh. J Cancer Metastasis Treat 2018;4:52 I http://dx.doi.org/10.20517/2394-4722.2018.51

(https://obamawhitehouse.archives.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-
medicine-initiative).

Earlier a very elaborate mix of population genetics, molecular genetics, and very complex statistical
[1]
approach was used to identify the gene(s) attributed to the development of cancer . BRCA1 and BRCA2
genes were localized on chromosomes 17 and 13 respectively, through this approach. The technique, known
as positional cloning, was very elaborate and yet proved evasive in the case of cancer and many other
polygenic diseases that are influenced by the environment as well. Subsequently, in the post-genomic era,
a whole genome scan from case-control studies revealed several “probable” genes likely to influence cancer
[2,3]
development, metastasis, and the treatment outcome . The genes and their variants associated with
cancer are found in all the major races and populations of the world, although their frequency occurrence
may slightly differ among various populations. Therefore, what really matters is more about one’s own
genetic background, than about which race or population one belongs to.

The human genome and its resultant tools and techniques have been tremendously useful in the cancer
management. Although the hope expressed by Bill Clinton is beyond the horizon at the moment, we have
learned many things about the origin of cancer cells, its spread and metastasis, and treatment. Perhaps the
most important lessons of the past two decades are: (1) cancer etiology is very complex and heterogeneous,
implying that the formation of cancer in two patients might have different molecular etiology. This is an
important consideration as the same treatment may not be equally effective for both the patients; and (2)
there is also heterogeneity of patient population implying that two patients, based on their genotypic and
[4]
phenotypic make-up may respond differently to the identical treatment protocol . The understanding that
there is tremendous variability in drug response which is emanating from the individual’s genetic and
metabolic variants gave rise to the science of pharmacogenetics.

Soon after the Human Genome Project, we saw a few individual genome analyses followed by massive
genome-wide exon scans that collectively have enormously enriched the data of the human genome. As
the scale of technologies expanded, the cost came down, and it became desirable as well as affordable to
use genetic testing for determining individual’s genetic susceptibility to develop cancer and thereby its
[5]
prevention, treatment regimen and its prognosis . In 2001, the cost of one genome sequence was about 100
million USD, which has now come down to about 1000 USD. With this price tag, a scan of one’s individual
[6]
genome has become a reality and may become a necessary tool in the health management .
Pharmacogenetics can play an important role in identifying responders and non-responders to medications,
[7]
avoiding adverse events, and optimizing drug dose. For example, Ciccolini et al. have summarized utility
of pharmacokinetic and pharmacogenetics in chemotherapy with gemcitabine. Realizing the importance
of genetic biomarkers, US FDA maintains the list of Pharmacogenomic Biomarkers for drug labeling
purpose (https://www.fda.gov/downloads/Drugs/ScienceResearch/UCM578588.pdf).Similarly, Genetic
Testing Registry from NCBI/NIH has 241 tests listed for cancer of which 64 are pharmacogenetic tests for
18 genetically influenced drug responses (e.g., tamoxifen, irinotecan, thioguanine, fluorouracil) (http://
www.ncbi.nlm.nih.gov/gtr/). As of now, there are dozens of companies which will test one’s DNA for the
susceptibility to a variety of cancers for about 200 USD. Their panel of genes may have from about 20
to 100 genes associated with a variety of cancers. Such pre-symptomatic testing which has tremendous
value in cancer prevention is slowly becoming acceptable and even desirable, especially if one of the
family members has been afflicted by cancer. One can debate about the number of gene variants on
the commercial tests, the fact is that the list can’t be exhaustive as it evolves with each new study, and
the complexity of “system biology” where gene products may exhibit compensatory functions in vivo. I
anticipate that for some genotyping tests, we may need it coupled with respective phenotying parameter in
the future.