RESUMO
XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair cross-complementing group 2) codon 751 polymorphisms were studied in esophageal squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood samples of 120 cases and 160 age-and-gender matching controls were collected from North India and the two polymorphisms were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques. The data were analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12-0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and statistically nonsignificantly (OR = 1.5) associated with increased risk of this cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR = 0.06, 95% CI = 0.007-0.605, P = 0.03), whereas ERCC2 (Lys/Gln-Gln/Gln) was marginally associated with increased risk (OR = 2.1, 95% CI = 0.46-9.44). Upon analysis of gene-gene interaction, a relationship was observed, although statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln-Gln/Gln)-ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09-1.16) and XRCC1 (Gln/Gln)-ERCC2 (Lys/Gln) (OR = 0.36, 95% CI = 0.11-1.17) and reduced risk of ESQCC in the North Indian population. These observations suggest that the Gln/Gln genotype of XRCC1 might play an important role in DNA repair in ESQCC.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/genética , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Polimorfismo Genético , Fumar/efeitos adversos , Proteína Grupo D do Xeroderma Pigmentoso/genética , Consumo de Bebidas Alcoólicas/genética , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Códon/genética , Reparo do DNA/genética , Feminino , Predisposição Genética para Doença , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fumar/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
DNA repair forms the most effective defense system against DNA damage. The XRCC1 gene product is implicated in single-strand and base-excision repair mechanisms. Our main aim was to investigate the relationship between the XRCC1 gene with lung cancer on the north-Indian population. Blood samples from 225 North-Indian subjects including 103 newly diagnosed cases and 122 population-based healthy persons were collected. XRCC1 genotypes were detected using a PCR-RFLP technique. The data were analyzed by logistic regression analysis. XRCC1 polymorphisms at codon 399 were found to be protective in the development of lung cancer (OR--0.6, 95% CI--0.46-0.80, p-0.0008). The codon 194 Trp/Trp genotype was associated with a slightly increased risk of lung cancer. When assessed in nonsmokers, only the Arg/Trp genotype of XRCC1 codon 194 was positively associated with lung cancer (OR--2.3, 95% CI--0.77-7.20). Smoking also seemed to significantly interact with the combined genotypes of XRCC1 codon 399 Arg/Gln/Gln/Gln. In conclusion, the results have suggested that the XRCC1 gene might be the risk genotype for lung cancer in this population.
Assuntos
Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos , Arginina/química , Arginina/genética , Estudos de Casos e Controles , Códon/genética , Reparo do DNA/genética , Feminino , Genótipo , Glutamina/química , Glutamina/genética , Humanos , Índia , Masculino , Polimorfismo de Fragmento de Restrição , População/genética , Risco , Triptofano/química , Triptofano/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.