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CYP1A1 Ile462Val polymorphism and colorectal cancer risk in Polish patients.

ABSTRACT: Colorectal cancer (CRC) is an epidemiological problem of a great importance in Poland; each year approximately 14,600 new cases of the disease are diagnosed. Mortality associated with CRC reaches approximately 10,400 cases per year (according to the National Cancer Registry). The 5-year survival rate is approximately 25 %, which is one of the lowest rates in Europe. The etiology of sporadic colorectal cancer (CRC) is multifactorial and has been attributed to an interplay between both environmental and genetic risk factors. In addition, there is a general consensus that genetic factors may modulate the influence of environmental insults. Following these assumptions, we performed a study on widely described polymorphisms in xenobiotic-metabolizing enzymes and DNA repair genes which may influence individual susceptibility to cancer. We selected five candidate polymorphisms in following genes: ERCC1 Asp118Asn (rs11615), XPC i11C/A (rs2279017), XRCC3 Met241Thr (rs861539) CYP1A1 Ile462Val (rs1048943) and NAT2 A803G (rs1208) and assessed the importance of chosen SNPs on groups consisting of 478 CRC patients and 404 controls. Only CYP1A1 Ile462Val was statistically significant in CRC patients over 50 years old: OR 2.05 (1.29-3.28); p = 1.25E-02 and this association was more pronounced in the female group of CRC patients after the age of 50: OR 2.72 (1.43-5.14); p = 1.14E-02.

SUBMITTER: Gil J

PROVIDER: S-EPMC4079939 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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CYP1A1 Ile462Val polymorphism and colorectal cancer risk in Polish patients.

Gil Justyna J Gaj Paweł P Misiak Błażej B Ostrowski Jerzy J Karpinski Pawel P Jarczyńska Alicja A Kielan Wojciech W Sasiadek Maria Malgorzata MM

Medical oncology (Northwood, London, England) 20140618 7

Colorectal cancer (CRC) is an epidemiological problem of a great importance in Poland; each year approximately 14,600 new cases of the disease are diagnosed. Mortality associated with CRC reaches approximately 10,400 cases per year (according to the National Cancer Registry). The 5-year survival rate is approximately 25 %, which is one of the lowest rates in Europe. The etiology of sporadic colorectal cancer (CRC) is multifactorial and has been attributed to an interplay between both environment ...[more]

PMID: 24939416

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Project description:ObjectiveCytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association be- tween single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population.Materials and methodsIn this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genom- ic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters.ResultsWe observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001), AG (57 vs. 78%, P=0.0002) and GG (5 vs. 6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs AG in major (33 vs 67%) and poor (62 vs 31%) hematological responders, and AA vs AG in major (34 vs. 65%) and poor (78 vs. 22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome.ConclusionThe higher frequency of AG in controls indicates that AG may play a protec- tive role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating that this polymorphism could serve as a good therapeutic marker in predicting response to such therapy.

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CYP1A1 Ile462Val polymorphism and colorectal cancer risk in Polish patients.

Publications

CYP1A1 Ile462Val polymorphism and colorectal cancer risk in Polish patients.

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