Alguacil Juan, Porta Miquel, Kauppinen Timo, Malats Núria, Kogevinas Manolis, Carrato Alfredo
Clinical and Molecular Epidemiology of Cancer Unit, Institut Municipal d'Investigació Mèdica (IMIM), Barcelona, Spain.
Int J Cancer. 2003 Nov 20;107(4):635-41. doi: 10.1002/ijc.11431.
ras genes are known critical DNA targets for chemical carcinogens. Exocrine pancreatic cancer (EPC) is the human tumor with the highest prevalence of K-ras mutations at diagnosis. We analyzed the relationship between past occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons (PAHs) and other agents and mutations in codon 12 of the K-ras gene in 107 incident cases of EPC. Information on occupational and life-style factors was obtained from personal interviews conducted during hospital stay. Occupational exposures were examined using industrial hygienists (IH) assessment and the Finnish job-exposure matrix (Finjem). Specific occupational exposures among K-ras mutated EPC cases (n = 83) were compared to those of K-ras wild-type EPC cases (n = 24) (case-case analysis). Multivariate-adjusted odds ratios (OR) and their corresponding 95% confidence limits were estimated by unconditional logistic regression. Cases with K-ras mutations were significantly more likely than wild-type cases to have been exposed to dyes and organic pigments (OR 4.8; p<0.05). There was some indication of weaker associations between K-ras mutations and occupational exposure to lead, PAHs, benzo[a]pyrene, gasoline, nickel, inhalatory exposure to chromium and sedentary work. The association with chromium compounds was stronger for G to T transversions, a finding compatible with experimental studies on mutation spectra for chromium. Results lend moderate support to the hypothesis of indirect relationships between occupational exposure to dyes and organic pigments and the activation of the K-ras gene in the etiopathogenesis of human exocrine pancreatic cancer.
ras基因是化学致癌物已知的关键DNA靶点。外分泌性胰腺癌（EPC）是诊断时K-ras突变发生率最高的人类肿瘤。我们分析了107例EPC新发病例中既往职业性接触染料、金属、多环芳烃（PAHs）及其他物质与K-ras基因第12密码子突变之间的关系。职业和生活方式因素信息通过住院期间的个人访谈获得。职业暴露采用工业卫生学家（IH）评估和芬兰工作暴露矩阵（Finjem）进行检查。将K-ras突变的EPC病例（n = 83）中的特定职业暴露与K-ras野生型EPC病例（n = 24）的职业暴露进行比较（病例对照分析）。通过无条件逻辑回归估计多变量调整后的优势比（OR）及其相应的95%置信区间。K-ras突变的病例比野生型病例更有可能接触过染料和有机颜料（OR 4.8；p<0.05）。有迹象表明K-ras突变与职业性接触铅、PAHs、苯并[a]芘、汽油、镍、吸入性接触铬和久坐工作之间的关联较弱。与铬化合物的关联在G到T颠换方面更强，这一发现与铬突变谱的实验研究结果相符。研究结果为职业性接触染料和有机颜料与人类外分泌性胰腺癌发病机制中K-ras基因激活之间存在间接关系这一假说提供了适度支持。
