GSTT1 null and MPO -463G>A Polymorphisms and Carboplatin Toxicity in an Indian Population

Bag, Arundhati; Pant, Nirdosh Kumar; Jeena, Lalit Mohan; Bag, Niladri; Jyala, Narayan Singh

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저자정보: Bag, Arundhati (Institute of Allied Health [Paramedical] Services, Education and Training) Pant, Nirdosh Kumar (Swami Ram Cancer Hospital and Research Center) Jeena, Lalit Mohan (Institute of Allied Health [Paramedical] Services, Education and Training) Bag, Niladri (Department of Plantation Management and Studies, Sikkim University) Jyala, Narayan Singh (Department of Biochemistry, Govt. Medical College)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제14권 제8호

발행연도: 2013.1

수록면: 4,739 - 4,742 (4page)

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Carboplatin, a second generation platinum drug, is widely used to treat different types of cancers. However, myelosuppression remains a major consideration in its use. Genetic polymorphisms of enzymes involved in drug disposition can influence therapeutic outcome. The homozygous null deletion of phase II metabolic gene GSTT1 that abolishes its xenobiotic- detoxifying ability may be associated with carboplatin toxicity. Further, since carboplatin generates oxidative stress, polymorphisms of oxidative stress genes that regulate the cellular level of free radicals may have important roles in generating drug- related adverse effects. We here investigated the null polymorphism of GSTT1, and the -463G>A promoter polymorphism of oxidative stress gene myeloperoxidase (MPO) for carboplatin toxicity in a population of northern India. Cancer patients who were treated with carboplatin, and developed toxicity was considered. The study group comprised of 10 patients who developed therapy- related adverse effects. Peripheral blood was taken from patients for DNA isolation. GSTT1 null genotype was determined by conducting duplex PCR and MPO-463 G>A was determined by PCR followed by RFLP. Hematologic toxicity was experienced by 5 patients, 2 of them had grade 3 and 4 toxicity and 3 others had grade 2 toxicity. They also had gastrointestinal (GI) toxicity. Remaining 5 individuals developed GI toxicity but no hematological toxicity. While GG homozygous of MPO was present in majority of patients having hematologic toxicity (in 4 out of 5 individuals), one A allele (AG genotype) was present in 4 patients who did not have any hematological toxicity. Thus variant A allele of MPO -463G>A may be related to lower hematological toxicity. These preliminary data, however, are required to be confirmed in larger studies along with other relevant polymorphisms.

#Carboplatin #GSTT1 #kumaun region #MPO #polymorphism #toxicity

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