Increased risk of intestinal type of gastric adenocarcinoma in Japanese women associated with long forms of CCTTT pentanucleotide repeat in the inducible nitric oxide synthase promoter.
ABSTRACT Tandem repeat number polymorphism of a CCTTT pentanucleotide in the promoter region of the inducible nitric oxide synthase gene (iNOS) and a polymorphism of the interleukin-1beta (IL-1B) promoter at position -31 were analyzed in DNA samples from 181 Japanese control subjects and 158 gastric cancer patients, including 96 intestinal type and 62 diffuse type. An association between the intestinal type of gastric adenocarcinoma and higher promoter activity of the iNOS gene was found in women, especially those having higher promoter activity of the IL-1B gene and without a history of smoking. Our results imply that chronic inflammation caused by excess nitric oxide generated by iNOS contributes to Helicobacter pylori-induced gastric cancer.
- [Show abstract] [Hide abstract]
ABSTRACT: We analyzed the associations of the NOS2 (CCTTT)n promoter polymorphism to lung cancer risk and tumor histology in smokers and non-smokers. We also investigated lung cancer long-term survival in relation to the polymorphism, smoking data, histology, age at diagnosis, and gender. One hundred eighty-five lung-cancer patients and 164 matched controls, where non-smokers were enriched among the lung cancer cases, were genotyped by fragment analysis and sequencing. Genotypes were combined with information on histology, patient smoking status, and cancer-specific death, using a 20-year follow-up. We divided the (CCTTT)n alleles into short (n ≤ 10), intermediate (n = 11-12), and long (n ≥ 13). Patients homozygous for short repeats had significantly increased risk of lung cancer (p = 0.030) compared to carriers of two long alleles (LL). Lack of long allele was associated with a significantly increased lung cancer risk overall (p = 0.011), especially among non-smokers (p = 0.001). A significantly higher lung cancer survival was seen in non-smokers compared to smokers (p = 0.046) and in low-dose smokers compared to high-dose smokers at the time of diagnosis (p = 0.028). Moreover, non-smoking patients with squamous cell carcinoma (p = 0.015) or adenocarcinoma (p = 0.024) showed a significantly lower survival compared to other lung carcinomas. Nitric oxide can induce proliferation as well as apoptosis depending on cellular context. Our results suggest that the (CCTTT)n NOS2 microsatellite may influence the risk of developing lung cancer, especially in non-smokers, possibly by affecting intracellular nitric oxide levels. Our results also give additional information about the yet poorly understood etiological and prognostic differences between lung cancer in non-smokers and smokers.Tumor Biology 01/2014; DOI:10.1007/s13277-013-1582-5 · 2.84 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: NAD(P)H:quinine oxidoreductase (NQO1) plays an important role in the metabolism of several carcinogens contained in cigarettes. Inducible nitric oxide synthase (iNOS) expression had been detected in urinary bladder tumors. The aim of this study was to investigate the interaction of iNOS and NQO1 on bladder cancer (BC) risk stratified by cigarette smoking status. A total of 159 BC patients and 150 cancer-free controls were recruited from December 2003 to November 2004. Genotyping of NQO1 rs1800566 polymorphism and iNOS (CCTTT)n pentanucleotide repeat polymorphism was determined using the polymerase chain reaction-restricted fragment length polymorphism and sequencing method. The odds ratio and 95% confidence interval (CI) were calculated as a measure of the joint effect of NQO1 rs1800566 and iNOS (CCTTT)n polymorphisms on BC risk among cigarette smokers. Compared with study participants carrying the C/C genotype of NQO1 gene, those with C/T and T/T genotypes had a significantly increased BC risk of 1.8 (95% CI = 1.1-2.9). Among cigarette smokers, those who carried the 12-repeat allele of iNOS (CCTTT)n polymorphism had a significantly increased BC risk of 2.7 (95% CI = 1.0-6.7). Furthermore, a significant combined effect of the C/T and T/T genotypes of NQO1gene and the 12-repeat allele of iNOS (CCTTT)n repeat polymorphism on BC was found among cigarette smokers (odds ratio = 4.4, 95% CI = 1.3-14.9). Our findings suggest that a significant combined effect of NQO1 C/T and T/T genotypes and the 12-repeat allele of iNOS (CCTTT)n polymorphism on BC exists, especially in those with the habit of cigarette smoking.Journal of the Chinese Medical Association 12/2013; 77(2). DOI:10.1016/j.jcma.2013.10.005 · 0.75 Impact Factor