Moore Lee E, Smith Allan H, Eng Clarence, DeVries Sandy, Kalman Dave, Bhargava Vivek, Chew Karen, Ferreccio Catterina, Rey Omar A, Hopenhayn Claudia, Biggs Mary Lou, Bates Michael N, Waldman Frederic M
Arsenic Health Effects Research Program, School of Public Health, University of California, 140 Warren Hall 7360, Berkeley, CA 7360, USA.
Carcinogenesis. 2003 Nov;24(11):1785-91. doi: 10.1093/carcin/bgg136. Epub 2003 Aug 14.
Previous studies demonstrated that tobacco and arsenic exposure are risk factors for bladder cancer. A case-case study was conducted to compare p53 mutations in 147 bladder tumors from South American patients by tobacco and arsenic exposure. Information on residential history and lifestyle factors was collected. The prevalence of p53 mutations and protein expression was examined in relation to tumor stage, grade, patient age, gender, tobacco and arsenic exposure. Smokers were grouped as ever/never smokers and by pack years of exposure (0, 1-20, >20). Patients were also grouped into four arsenic exposure categories based on the average of the five highest years arsenic concentration in their drinking water: group 1, non-detectable to <10 microg/l (n = 50); group 2, 10-99 microg/l (n = 31); group 3, 100-299 microg/l (n = 35); group 4, >300 microg/l (n = 30). The proportion of tumor samples with p53 mutations and P53 immunopositivity increased strongly with both stage and grade, but not with arsenic exposure or smoking. The prevalence of tumors containing mutational transitions increased markedly with tumor stage (from 14 to 52%, P(trend) = 0.005) and grade (from 11 to 48%, P(trend) = 0.004) and was higher in smokers than in non-smokers (34 versus 18%, respectively, P = 0.10). An increasing trend was observed with pack years of smoking (P = 0.09). The majority of mutations in tumors from both smokers and non-smokers were G-->A transitions, however, in smokers a preference for G-->A transitions at CpG sites was observed (P = 0.07, two-tailed) and a positive trend was observed with pack years of exposure (P = 0.04). A hotspot was found at codon 273 in 12% of the tumors from smokers but was not observed in never smokers (P = 0.05) and a positive trend was observed with pack years of tobacco exposure (P = 0.001). Neither stage nor grade demonstrated a preference for CpG site mutation, suggesting that these changes may be early exposure-related events in carcinogenesis and are not related to tumor progression. Arsenic exposure was not associated with an increased prevalence of p53 mutation or P53 immunopositivity and there was no evidence of interaction between arsenic and smoking with these outcome variables.
以往研究表明，接触烟草和砷是膀胱癌的风险因素。开展了一项病例对照研究，比较147例来自南美患者的膀胱肿瘤中因接触烟草和砷而导致的p53突变情况。收集了居住史和生活方式因素方面的信息。研究了p53突变和蛋白表达的患病率与肿瘤分期、分级、患者年龄、性别、烟草和砷接触之间的关系。吸烟者分为曾经吸烟/从不吸烟两组，并根据吸烟包年数（0、1 - 20、>20）进行分组。患者还根据其饮用水中五年最高砷浓度的平均值分为四类砷接触组：第1组，未检测到至<10微克/升（n = 50）；第2组，10 - 99微克/升（n = 31）；第3组，100 - 299微克/升（n = 35）；第4组，>300微克/升（n = 30）。p53突变和P53免疫阳性的肿瘤样本比例随分期和分级显著增加，但与砷接触或吸烟无关。含有突变转换的肿瘤患病率随肿瘤分期（从14%增至52%，P趋势 = 0.005）和分级（从11%增至48%，P趋势 = 0.004）显著增加，且吸烟者高于不吸烟者（分别为34%和18%，P = 0.10）。吸烟包年数呈上升趋势（P = 0.09）。吸烟者和不吸烟者肿瘤中的大多数突变都是G→A转换，然而，在吸烟者中观察到在CpG位点更倾向于G→A转换（P = 0.07，双侧），且与吸烟包年数呈正相关趋势（P = 0.04）。在12%的吸烟者肿瘤中发现密码子273处有一个热点，但在从不吸烟者中未观察到（P = 0.05），且与烟草暴露包年数呈正相关趋势（P = 0.001）。分期和分级均未显示出对CpG位点突变的偏好，这表明这些变化可能是致癌过程中早期暴露相关事件，与肿瘤进展无关。砷接触与p53突变或P53免疫阳性患病率增加无关，且没有证据表明砷与吸烟在这些结果变量上存在相互作用。
