Glutathione S-Transferase Gene Polymorphism and Its Susceptibility to Gastrointestinal Cancer: A CaseControl Study from South-Western Maharashtra
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Author:
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MADHAVI N PATIL, PARIXIT BHANDURGE, RASHMI GUDUR, ANAND GUDUR, SANDEEP KADAM, SURAJ PAWAR, SATISH KAKADE, KAILAS D DATKHILE
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Abstract:
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Environmental and man made carcinogens has become one of the major health concerns worldwide which is
responsible for various disorders in humans. Human body metabolize these carcinogens by phase I and II
metabolic enzymes. Genetic polymorphism in the phase II metabolic enzymes i.e Glutathione Stransferase(GST), have been found to be responsible for increasesd susceptibility to carcinogenesis. In the
present case-control study, 200 confirmed gastrointestinal (GI) cancer patients and equally disease free, age
and gender-matched controls were analyzed to study the polymorphism in GST genes using polymerase chain
reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. We assessed the independent and
combined effects of GSTM1, GSTT1 and GSTP1 on the risk of GI cancer and their interaction with
environmental factors. The independent effect of GSTM1 null genotype (OR: 1.87; CI: 1.25-2.80; P=0.002) &
GSTT1 null genotype (OR: 3.48; CI: 2.19-5.25; P<0.0001) were found to be significantly associated with the
increased risk of GI cancer. Similarly, combined analysis of GSTM1 null and GSTT1 null also showed risk of
developing GI cancer. GSTP1 exon 5 and exon 6 variant genotypes in combination with GSTM1 & GSTT1
conferred a risk of developing GI cancer among the patients. When the analysis was performed on the basis of
age and tobacco history, the risk of GI cancer was observed in the subjects above the age of 50 years, while no
gene- tobacco interaction was found to be associated with altered GI cancer risk. These findings indicate that
GSTM1 and GSTT1 but not GSTP1 ex 5 and ex 6, modulate the risk of GI cancer among the study population.
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Keyword:
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Gastrointestinal Cancer, Genetic polymorphism, GSTM1, GSTT1, GSTP1, PCR-RFLP
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EOI:
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DOI:
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https://doi.org/10.31838/ijpr/2021.13.02.489
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