Association of genetic polymorphism of glutathione S-transferases with colorectal cancer susceptibility in snuff (Naswar) addicts / Associação de polimorfismo genético de glutationa S-transferase com suscetibilidade ao câncer colorretal em viciados em rapé (Naswar)

The current study aimed to investigate the relationship between polymorphisms in detoxifying (GSTM1, GSTT1, and GSTP1) genes and their association with colorectal cancer (CRC) in tobacco addicts of Pashtun ethnicity. Polymorphisms in the selected genes were genotyped in a case-control study consisting of 100 histologically confirmed male CRC patients and 100 birth-year and gender-matched healthy controls using the PCR−RFLP method. The GSTM1 null, and GSTT1 null genotypes were significantly contributed to the risk of CRC in the cases (OR= 3.131, 95% CI: 1.451−6.758, P = 0.004, and OR= 3.541, 95% CI: 1.716−7.306, P = 0.001, respectively), whereas the association observed for GSTP1 Val/Val (1.139, 95% CI: 0.356−3.644, P = 0.826) did not show statistical significance. The combined GSTM1 null and GSTT1 null showed a 41-fold increased risk (95% CI: 4.945−351.950, P = 0.001), while, the combined GSTM1 null and GSTP1 Ile/Val or Val/Val variant genotypes exhibited about 3-fold (95% CI: 1.196−7.414, P = 0.019) increased risk to CRC. Similarly, the combined GSTT1 null and GSTP1 Ile/Val or Val/Val variant genotypes showed about a 3-fold (95% CI: 1.285−8.101, P = 0.013) increased risk of CRC. In the combination of three GST genotypes, the GSTM1 null, GSTT1 null, and GSTP1 Ile/Val or Val/Val variant genotypes demonstrated a more than a 22-fold (95% CI: 2.441−212.106, P = 0.006) increased risk of CRC. Our findings suggest that GSTM1 and GSTT1 polymorphism and its combination with GSTP1 may be associated with CRC susceptibility in the Naswar addicted Pashtun population of Khyber Pakhtunkhwa, Pakistan.

O presente estudo teve como objetivo investigar a relação entre polimorfismos em genes desintoxicantes (GSTM1, GSTT1 e GSTP1) e sua associação com câncer colorretal (CCR) em tabagistas da etnia pashtun. Os polimorfismos nos genes selecionados foram genotipados em um estudo de caso-controle composto por 100 pacientes do sexo masculino com CCR, confirmados histologicamente, e 100 controles saudáveis, ​​pareados por ano de nascimento e sexo usando o método PCR-RFLP. Os genótipos GSTM1 nulo e GSTT1 nulo contribuíram significativamente para o risco de CCR nos casos (OR = 3,131, IC 95%: 1,451-6,758, P = 0,004; OR = 3,541, IC 95%: 1,716-7,306, P = 0,001, respectivamente), enquanto a associação observada para GSTP1 Val/Val (1,139, IC 95%: 0,356-3,644, P = 0,826) não apresentou significância estatística. O GSTM1 nulo e o GSTT1 nulo combinados mostraram um risco 41 vezes maior (IC 95%: 4,945-351,950, P = 0,001) para CCR, enquanto os genótipos GSTM1 nulo e GSTP1 Ile/Val ou Val/Val combinados apresentaram risco cerca de 3 vezes maior (IC 95%: 1,196-7,414, P = 0,019) para CCR. Da mesma forma, os genótipos combinados GSTT1 nulo e GSTP1 Ile/Val ou Val/Val tiveram um risco para CRC cerca de 3 vezes maior (95% CI: 1,285-8,101, P = 0,013). Na combinação de três genótipos GST, os genótipos GSTM1 nulo, GSTT1 nulo e GSTP1 Ile/Val ou Val/Val apresentaram um risco 22 vezes maior (IC 95%: 2,441-212,106, P = 0,006) para CRC. Nossos achados sugerem que o polimorfismo GSTM1 e GSTT1 e sua combinação com GSTP1 podem estar associados à suscetibilidade ao CRC da população pashtun de Khyber Pakhtunkhwa, Paquistão, viciada em Naswar.

Association of genetic polymorphism of glutathione S-transferases with colorectal cancer susceptibility in snuff (Naswar) addicts.

The current study aimed to investigate the relationship between polymorphisms in detoxifying (GSTM1, GSTT1, and GSTP1) genes and their association with colorectal cancer (CRC) in tobacco addicts of Pashtun ethnicity. Polymorphisms in the selected genes were genotyped in a case-control study consisting of 100 histologically confirmed male CRC patients and 100 birth-year and gender-matched healthy controls using the PCR-RFLP method. The GSTM1 null, and GSTT1 null genotypes were significantly contributed to the risk of CRC in the cases (OR= 3.131, 95% CI: 1.451-6.758, P = 0.004, and OR= 3.541, 95% CI: 1.716-7.306, P = 0.001, respectively), whereas the association observed for GSTP1 Val/Val (1.139, 95% CI: 0.356-3.644, P = 0.826) did not show statistical significance. The combined GSTM1 null and GSTT1 null showed a 41-fold increased risk (95% CI: 4.945-351.950, P = 0.001), while, the combined GSTM1 null and GSTP1 Ile/Val or Val/Val variant genotypes exhibited about 3-fold (95% CI: 1.196-7.414, P = 0.019) increased risk to CRC. Similarly, the combined GSTT1 null and GSTP1 Ile/Val or Val/Val variant genotypes showed about a 3-fold (95% CI: 1.285-8.101, P = 0.013) increased risk of CRC. In the combination of three GST genotypes, the GSTM1 null, GSTT1 null, and GSTP1 Ile/Val or Val/Val variant genotypes demonstrated a more than a 22-fold (95% CI: 2.441-212.106, P = 0.006) increased risk of CRC. Our findings suggest that GSTM1 and GSTT1 polymorphism and its combination with GSTP1 may be associated with CRC susceptibility in the Naswar addicted Pashtun population of Khyber Pakhtunkhwa, Pakistan.