preventive colectomy in patients at high risk for developing colorectal cancer.^12
Genetic determinants of other gastrointestinal and associated malignancies are
being studied as well.^13
Pharmacogenomic testing of UDP glucuronyltransferase (UGT), an enzyme that
inactivates the active form of irinotecan and a first line chemotherapy agent for the
treatment of colorectal cancer, can be applied to modify the drug dosage and reduce
the incidence of toxic side effects (neutropenia, diarrhea) of irinotecan.^14 Similar
tests are conducted for the DPYD gene whose protein product (DPY) participates in
the inactivation of 5-fluorouracil, another important chemotherapeutic agent in
colorectal cancer treatment.^15 Focused pharmacogenetics testing can also serve in
assessing the effectiveness of chemotherapy, as is the case with variants of DNA
repair genes XRCC1, ERCC1, ERCC2, glutathione-S-transferase, and the response
to oxaloplatin therapy.^16
Polymorphisms of the interleukin-28B gene significantly influence the course of
the hepatitis C infection and the response to interferon and ribavirin therapy. The
presence of the protective form of the gene (allele C) leads to a twofold increase in
the efficiency of the therapy. Its more frequent occurrence in Europeans compared
to Africans partly explains the difference in the course of the disease and the
treatment response between the two races.^17 The protein product, interleukin 28B,
belongs both to the cytokine and the interferon family, while its receptor belongs to
the interleukin-10-like family. Still, the antiviral mechanism (the effect on hepatitis
C virus, enhanced effectiveness of vaccination against influenza virus when com-
bined) has not been clarified.^18 Clear impact on clinical practice has been confirmed
by recent guidelines of the European Association for the Study of the Liver (EASL),
but the obligatory determination of IL-28B polymorphism status prior to initiation
of therapy has not been issued, partly due to the limited availability of the method.^19
Long-standing chronic infection with hepatitis viruses (B and C) will in time
progress to liver cirrhosis and hepatocellular carcinoma (HCC) in predisposed
patients. Genome-wide association studies (GWAS) are employed in an attempt
to identify genes that increase or indicate an increased risk of HCC, so far with
modest results.^20
H. pyloriassociated diseases (gastritis, peptic ulcer disease, gastric adenocarci-
noma, gastric lymphoma) are another area of interest of personalized medicine.
Colonization, virulence, and the clinical manifestation are in connection to the
(^12) Patel and Babyatsky ( 2008 ).
(^13) Lynch et al. ( 2010 ) and Chao ( 2012 ).
(^14) Ramchandani et al. ( 2007 ).
(^15) Yen and McLeod ( 2007 ).
(^16) Saito and Camilleri ( 2006 ).
(^17) Ge et al. ( 2009 ).
(^18) Morrow et al. ( 2009 ).
(^19) European Association for the Study of the Liver ( 2014 ).
(^20) Miki et al. ( 2012 ).
260 D. Sˇtimac and N. Franjic ́