@article{ad40c79db3c74c1eb185b25dca1fe749,
title = "Genetic Susceptibility to Squamous Cell Carcinoma of the Lung in Relation to Cigarette Smoking Dose",
abstract = "Cytochrome P450IA1 is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke; an association of lung cancer with DNA polymorphisms of P450IA1 gene was shown in our previous study. In this paper, we investigated the interindividual difference of geneti cally determined susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. We tirsi compared the total amounts of cigarettes consumed over the lifetime of patients and showed that the patients with a “susceptible” P450IA1 gene genotype contracted carci noma after fewer cigarettes (mean ± SD, 31.3 ±12.8 x 10^4 cigarettes (n = 12)] than those with other genotypes [42.5 ±18.2 x 10^4(n = 33)], with a statistical significance of P < 0.05. Next, we carried out a casecontrol study to estimate the odds ratios of susceptible to nonsusceptible individuals in relation to the cumulated cigarette dose. We thus showed that the individuals with the susceptible genotype were at remarkably high risk with an odds ratio of 7.31 (95% confidence interval, 2.13 to 25.12) at a low dose level of cigarette smoking and that the difference in susceptibility between genotypes was reduced at high dose levels.",
author = "Kei Nakachi and Kazue Imai and Hayashi, {Shin ichi} and Junko Watanabe and Kaname Kawajiri and Hayashi, {Shin ichi} and Junko Watanabe and Kaname Kawajiri",
note = "Funding Information: Cardona C. Rabbitts PH. Spindel ER, Ghatei MA, Bleehen NM et al. Medical Research Council, Clinical Oncology and Radiotherapeulics Unir, MRC Cenrre, Hills Road, Cambridge CB2 2QH. Cancer Res 1991:51:5205-11. Gastrin-releasing peptide (GRP), a mammalian bombesin-like pep tide, has been shown to be an important autocrine growth factor for small cell lung cancer (SCLC). However, not all SCLC cell lines express the GRP gene or respond mitogenically to GRP stimulation, suggesting the existence of other autocrine pathways in this tumor. Neuromedin B (NMB), the mammalian counterpart of amphibian mnatensin, has been shown to be a mitogen for SCLC cell lines in vitro. TO determine whether NMB is a potential autcxrine growth factor for lung tumors, NMB gene expression, peptide synthesis, and secretion have been investigated in a panel of SCLC and non-SCLC (NSCLC) cell lines. Northern blot analysis and enzymatic amplification from mRNA by polymerase chain reaction showed that the NMB gene was expressed in all SCLC and NSCLC cell lines examined. In contrast, the GRP gene was expressed in four of six classic SCLC cell lines but not in variant SCLC or NSCLC cell lines. lmmunoreactive NMB was detected by radioimmunoassay in the majority of classic SCLC, in one of three variant SCLC and in one of three NSCLC cell lines, and secreted NMB was detected in medium conditioned by a SCLC and a NSCLC cell line. The present study also demonstrated the presence of lmmunoreactive GRP in the absence of detectable GRP gene expression. The antiserum used in the GRP radioimmunoassay failed to cross-react with NMB but showed some cross-reactivity with amphibian phyllolitorin raising the possibility that certain SCLC cell lines may produce a phyllolitorin-like peptide.",
year = "1991",
month = oct,
language = "English",
volume = "51",
pages = "5177--5180",
journal = "Cancer Research",
issn = "0008-5472",
number = "19",
}
