RESUMEN

BACKGROUND: Null genetic polymorphism of Glutathione S-transferase T1 (GSTT1) and -463 G>A promoter polymorphism of myeloperoxidase (MPO) were studied for association with lung cancer. MATERIALS AND METHODS: In a case- control study 26 lung cancer patients and 33 healthy individuals from hilly Kumaun region of northern India were investigated. DNA was extracted from peripheral blood. GSTT1 null polymorphism was detected by duplex PCR, and MPO polymorphism was detected by performing PCR-RFLP. RESULTS: An increased but statistically non- significant risk for lung cancer was found for GSTT1 null genotype. No association for MPO -463G>A genotype was evident. CONCLUSION: Further study with large sample size may reveal such association in this population.

RESUMEN

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.

Asunto(s)

Antineoplásicos/efectos adversos , Carboplatino/efectos adversos , Glutatión Transferasa/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Peroxidasa/genética , Polimorfismo Genético/genética , Estudios de Seguimiento , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/genética , Genotipo , Enfermedades Hematológicas/inducido químicamente , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/epidemiología , Enfermedades Hematológicas/genética , Humanos , India/epidemiología , Neoplasias/epidemiología , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/epidemiología , Síndrome Nefrótico/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico

RESUMEN

A survey was conducted to determine the cancer profile in Nainital and adjoining districts of Uttarakhand. Epidemiological information was collected from the records of patients with confirmed cancer cases. A total of 354 cases were studied for the year 2010. Lung cancer was found to be leading cancer type (17.23%) overall. Breast cancer was most prevalent in females (22.29%) followed by cervical (14.86%) and ovarian cancers (13.51%). Men were mainly suffering from tobacco- and alcohol-related cancers, e.g., lungs (26.21%), larynx (11.16%), oropharynx (9.7%), oral cavity (6.79%), and esophagus (6.79%). Cancers of unknown primary site (1.41%) were also detected.