ABSTRACT
BACKGROUND: Genetic polymorphisms of DNA repair enzymes in the base excision repair (BER) pathway, may lead to genetic instability and lung cancer carcinogenesis. We investigated the interactions among the gene polymorphisms in DNA repair genes and lung cancer. METHODS: We analyzed associations among OGG1 Ser326Cys and MUTYH Gln324His gene polymorphisms in relation to lung cancer risk using PCR-RFLP. The study involved 108 lung cancer patients and 121 non-cancer controls divided into non-smokers, smokers according to pack-years smoked in Japanese. RESULTS: The results showed that the MUTYH His/His genotype compared with Gln/Gln genotype showed an increased risk for lung cancer (adjusted odds ratio [OR] 3.03, confidence interval [95%CI], 1.31-7.00, p = 0.010), whereas there was no significant increase for the Gln/His genotype (adjusted OR 1.35, 95%CI 0.70-2.61, p = 0.376). The MUTYH His/His genotype was at a borderline increased risk for both adenocarcinoma and squamous cell carcinoma (adjusted OR 2.50, 95%CI 0.95-6.62, p = 0.065 for adenocarcinoma; adjusted OR 3.20, 95%CI 0.89-11.49, p = 0.075 for squamous cell carcinoma, respectively). However, the OGG1 Ser/Cys or Cys/Cys genotypes compared with the Ser/Ser genotype did not have significantly increased risk for lung cancer, containing either adenocarcinoma or squamous cell carcinoma. The joint effect of tobacco exposure and the MUTYH His/His genotype compared with the Gln/Gln genotype showed a significant association with lung cancer risk in smokers, and there was not significantly increased in non-smokers (adjusted OR 3.82, 95%CI 1.22-12.00, p = 0.022 for smokers; adjusted OR 2.60, 95%CI 0.60-11.25, p = 0.200 for non-smokers, respectively). The effect of tobacco exposure and the OGG1 Ser326Cys showed also no significant risk for lung cancer. CONCLUSION: Our findings suggest that the MUTYH Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population.
Subject(s)
DNA Glycosylases/genetics , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Aged , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Japan/epidemiology , Male , Middle Aged , Polymorphism, Genetic , Risk Factors , Smoking/genetics , Smoking/metabolismABSTRACT
BACKGROUND: Genetic polymorphisms of DNA repair enzymes may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interactions between polymorphisms of repair genes and tobacco smoking in colorectal cancer. METHODS: The case-control study involved sixty-eight colorectal cancer patients and 121 non-cancer controls divided into non-smokers and smokers according to pack-years of smoking. The genetic polymorphisms of DNA repair enzymes,OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu and XRCC1 Arg399Gln, were examined using PCR-RFLP. RESULTS: The MUTYH Gln324His showed strong significant associations with a risk of colorectal cancer (crude odds ratio [OR] 3.30, 95% confidence interval [95%CI] 1.44-7.60, p = 0.005; adjusted OR3.53, 95%CI 1.44-8.70, p = 0.006). The ORs for the APEX1 Asp148Glu were statistically significant (crude OR 2.69, 95%CI 1.45-4.99, p = 0.002; adjusted OR 2.33, 95%CI 1.21-4.48, p = 0.011). The ORs for the MUTYH Gln324His and the APEX1 Asp148Glu were statistically significant for colon cancer (adjusted OR 3.95, 95%CI 1.28-12.20, p = 0.017 for MUTYH Gln324His ; adjusted OR 3.04, 95%CI 1.38-6.71, p = 0.006 for APEX1 Asp148Glu). The joint effect of tobacco exposure and the MUTYH Gln324His showed a significant association with colorectal cancer risk in non-smokers (adjusted OR 4.08, 95%CI 1.22-13.58, p = 0.022) and the APEX1 Asp148Glu was significantly increased in smokers (adjusted OR 5.02, 95%CI 1.80-13.99, p = 0.002). However, the distributions of OGG1 Ser326Cys and XRCC1 Arg399Gln were not associated with a colorectal cancer risk. CONCLUSION: Our findings suggest that the MUTYH Gln324His and the APEX1 Asp148Glu constitutes an increased risk of colorectal cancer, especially colon cancer. The MUTYH Gln324His is strongly associated with colorectal cancer susceptibility in never smoking history, whereas the APEX1 Asp148Glu genotype constitutes an increased risk of colorectal cancer when accompanied by smoking exposure.
Subject(s)
Colorectal Neoplasms/genetics , DNA Glycosylases/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Polymorphism, Genetic , Smoking/adverse effects , Aged , Asian People/genetics , Aspartic Acid/genetics , Case-Control Studies , Colorectal Neoplasms/epidemiology , Female , Genetic Predisposition to Disease , Genotype , Glutamic Acid/genetics , Glutamine/genetics , Histidine/genetics , Humans , Male , Middle Aged , Smoking/geneticsABSTRACT
We investigated the associations between lung cancer and the gene polymorphisms of the drug metabolizing enzymes, containing cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2), glutathione S-transferase class mu (GSTM1), and N-acetyltransferase 2 (NAT2). The study involved 113 lung cancer patients and 121 non-cancer controls divided into never, light and heavy smokers according to pack-years of smoking in Japanese by using PCR-RFLP. For light smokers, the lung cancer risk of NAT2 intermediate-slow was significantly increased [the adjusted odds ratio (OR): 10.9, 95% confidence intervals (95%CI): 1.75-67.5, P-value: 0.010]. Moreover, never smokers having joint genotypes of NAT2 intermediate-slow and CYP1A2*1F A/A was also associated with increased the lung cancer risk (OR: 4.95, 95% CI: 1.19-20.6, P-value: 0.028). We suggested that light smokers with intermediate-slow NAT2 activity were at highest risk for lung cancer and the gene-gene interaction based on intermediate-slow NAT2 activity and high CYP1A2 activity would be increased a lung cancer risk among never smokers.
Subject(s)
Arylamine N-Acetyltransferase/genetics , Cytochrome P-450 CYP1A2/genetics , Lung Neoplasms/genetics , Polymorphism, Genetic/genetics , Smoking/adverse effects , Adenocarcinoma/epidemiology , Adenocarcinoma/genetics , Aged , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/genetics , Case-Control Studies , Female , Genotype , Glutathione Transferase/genetics , Humans , Japan , Lung Neoplasms/epidemiology , Male , Middle Aged , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Factors , Surveys and Questionnaires , Time FactorsABSTRACT
BACKGROUND/AIMS: The effect of lymph node metastasis around the splenic artery on the prognosis of proximal gastric cancer patients is not confirmed. The aim of this study is to clarify the optimal procedure for lymph node dissection along the splenic artery in proximal gastric cancer. METHODOLOGY: Proximal gastric cancer patients who underwent total gastrectomy with pancreaticosplenectomy were examined. The anatomical location of lymph nodes and the metastases around the pancreas were also studied in pancreatic cancer patients who underwent total pancreatectomy. RESULTS: Multivariate analysis of lymph node metastasis around the splenic artery showed that No. 11 lymph node metastasis was affected by No.10 lymph node that was predicted by depth of invasion. Multivariate analysis of prognostic variables by Cox's proportional hazard regression revealed that No. 10 lymph node metastasis was the significant factor affecting prognosis. No lymph node metastasis infiltrating the pancreatic parenchyma was observed in the pancreatic body or the tail. CONCLUSIONS: Total gastrectomy preserving the pancreas and spleen is the optimal procedure in proximal T2 gastric cancer. Total gastrectomy with splenectomy is appropriate in T3 cases, and distal pancreatectomy should be additionally done only in cases of direct invasion by the lymph node and/or the tumor to the pancreas.
