Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancer

Hiljadnikova-Bajro, Marija; Josifovski, Toni; Panovski, Milco; Јankulovski, Nikola; Nestorovska, Aleksandra Kapedanovska; Matevska, Nadica; Petrusevska, N; Dimovski, Aleksandar

doi:10.1016/j.cancergen.2012.01.015

Cited by 29 publications

(11 citation statements)

References 25 publications

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“…Contradictory results were published by the Macedonian authors Bajro et al [201], with a higher frequency of homozygous [(TA)7/7]+heterozygous [(TA)6/7] carriers compared with wild-type [(TA)6/6] in patients with CRC. The same effect was detected when only men were considered and no differences were found for women [201]. The same effect was detected when only men were considered and no differences were found for women [201].…”

Section: Bilirubin and Cancermentioning

confidence: 89%

“…The (TA)7/7 polymorphism status of individuals should be considered very carefully because a higher frequency of cancer-associated, kinetochore-positive MNi has been reported in homozygous carriers, but only in smokers [206]. In this context, the condition of reduced UGT1A1 activity in individuals with GS may reduce detoxification of phytochemicals, drugs and other toxic substances, and could be responsible for some of the positive associations between GS and cancer that have been reported [195,201,203].…”

Section: Bilirubin and Cancermentioning

confidence: 99%

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Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

et al. 2015

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Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.

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Section: Bilirubin and Cancermentioning

confidence: 89%

Section: Bilirubin and Cancermentioning

confidence: 99%

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

et al. 2015

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“…For the SULT1A1 (638G>A) polymorphism, approximately one-third of the population from the Republic of Macedonia carry the low-activity SULT1A1*2 allele and 17.0% are predicted to be homozygous for the SULT1A1*2 genetic variant [ 29 ] ( Table 3 ). The distributions of the UDP-glucuronosyltransferase (UGT)1A1*28 allele and genotype frequencies in our population are summarized in Table 3 [ 30 ]. Regarding the GSTT1 genotype distribution, 16 (0.13) out of 128 study subjects were predicted to carry the null genotype.…”

Section: Genetic Variants Associated With a Variable Drug Responsementioning

confidence: 99%

Distribution of the Most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia

Nestorovska

Jakovski

Naumovska

et al. 2014

Balkan Journal of Medical Genetics

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Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs) and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response.This study summarizes our current knowledge about the frequency distribution of the most common allelic variants in three broad gene categories: the Phase I oxidation-cytochrome P450 (CYP450) family (CYP2C9, CYP2C19, CYP3A5, CYP2D6); the Phase II conjugation (GSTT1, SULT1A1; UGT1A1) and drug target (TYMS-TSER, MTHFR and VKORC1) in the population of the Republic of Macedonia and compares the information obtained with data published for other indigenous European populations.Our findings define the population of the Republic of Macedonia as an ethnic group with a highly polymorphic genetic profile. These results add to the evidence regarding the distribution of clinically important variant alleles in DME and drug target genes in populations of European ancestry.

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“…[4–7] SN-38, irinotecan's active metabolite, is eliminated via UGT isoforms, among them, UGT1A1 pathway. [8] Also, higher risk for breast [9] and colorectal [10] cancers has been reported in GS, most probably as a result of carcinogens detoxification decrease [11,12] and estrogen-related disease. [13] …”

Section: Introductionmentioning

confidence: 99%

UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients

Souza

Vaisberg²,

Abreu³

et al. 2017

Medicine

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Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1∗28 (UGT1A1∗28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions’ to the liver disease scenario. Our aim was to assess UGT1A1 genotypes’ frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case–control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)–polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine–adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1∗28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1∗28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.

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Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancer

Cited by 29 publications

References 25 publications

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

Distribution of the Most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia

UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients

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