Sarebø Mona, Skjelbred Camilla F, Breistein Rebecca, Lothe Inger Marie B, Hagen Per Chr, Bock Gunter, Hansteen Inger-Lise, Kure Elin H
Telemark University College, Faculty of Arts and Sciences, Hallvard Eikas plass, 3800 Bø i Telemark, Norway.
BMC Cancer. 2006 Mar 17;6:71. doi: 10.1186/1471-2407-6-71.
The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (APC) gene has been reported to have a "gatekeeper" function in the colonic mucosa.
To evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in the APC gene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of the APC gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin.
The mutational spectra of the APC gene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and "ever smoking" OR = 1.73 (95% CI 0.83-3.58). For CRC cases several smoking parameters for dose and duration were used. We detected an association for all smoking parameters and "duration of smoking > 30 years", yielded a statistically significant OR = 2.86 (1.06-7.7). When cases were divided based on APC truncation mutation status, an association was detected in adenomas without APC mutation in relation to "ever smoking", with an OR = 3.97 (1.26-12.51). For CRC cases without APC mutation "duration of smoking > 30 years", yielded a statistically significant OR = 4.06 (1.20-13.7). The smoking parameter "starting smoking > or = 40 years ago" was only associated with CRC cases with APC mutations, OR = 2.0 (0.34-11.95). A case-case comparison revealed similar findings for this parameter, OR = 2.24 (0.73-6.86).
Our data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without APC truncation mutation. This may implicate other factors in development of these tumors. The association detected between smoking and CRC cases with APC mutation was in relationship to the smoking parameter "starting smoking > or = 40 years ago", a time period long enough to proceed CRC initiation.
结直肠癌（CRC）与吸烟之间的关联并不一致。有人提出吸烟史不完整以及与特定类型的CRC肿瘤的关联可作为解释。据报道，腺瘤性息肉病（APC）基因在结肠黏膜中具有“守门人”功能。
为了评估吸烟与腺瘤和癌发生相关的假设，并进一步研究这种关联是否归因于APC基因的突变，我们使用了一个由133例患者（45例腺瘤和88例癌）和334例对照组成的研究人群。对所有肿瘤的APC基因的突变簇区域（MCR）进行测序。病例和对照均来自挪威血统的同质队列。
APC基因的突变谱显示，根据曾经吸烟和从不吸烟状态，病例中的突变频率没有差异。腺瘤的总体病例对照关联被检测到，“曾经吸烟”的比值比（OR）=1.73（95%可信区间0.83 - 3.58）。对于CRC病例，使用了几个关于吸烟剂量和持续时间的参数。我们检测到所有吸烟参数与“吸烟持续时间>30年”之间的关联，得出具有统计学意义的OR = 2.86（1.06 - 7.7）。当根据APC截短突变状态对病例进行划分时，在无APC突变的腺瘤中检测到与“曾经吸烟”相关的关联，OR = 3.97（1.26 - 12.51）。对于无APC突变的CRC病例，“吸烟持续时间>30年”得出具有统计学意义的OR = 4.06（1.20 - 13.7）。吸烟参数“40年前及更早开始吸烟”仅与具有APC突变的CRC病例相关，OR = 2.0（0.34 - 11.95）。病例 - 病例比较显示该参数有类似结果，OR = 2.24（0.73 - 6.86）。
我们的数据表明吸烟与腺瘤和CRC发生之间存在关联。这种关联在无APC截短突变的病例中最为强烈。这可能意味着这些肿瘤的发生涉及其他因素。在具有APC突变的CRC病例中检测到的吸烟与CRC之间的关联与吸烟参数“40年前及更早开始吸烟”有关，这是一个足够长的时间段，足以启动CRC的发生。
