Chan Andrew T, Tranah Gregory J, Giovannucci Edward L, Hunter David J, Fuchs Charles S
Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Clin Gastroenterol Hepatol. 2004 Aug;2(8):704-12. doi: 10.1016/s1542-3565(04)00294-0.
BACKGROUND & AIMS: Regular aspirin use is associated with a reduced risk for colorectal adenoma, whereas smoking increases risk. The cytochrome P-450 (CYP) 2C9 (CYP2C9) enzyme is involved in the metabolism of several drugs, including possibly aspirin, and such carcinogens as smoking-related polycyclic aromatic hydrocarbons. Genetic variation in this enzyme may modulate the influence of aspirin and smoking on adenoma risk.
We examined the risk for incident distal colorectal adenoma according to CYP2C9 genotype, aspirin use, and smoking in a prospective nested case-control study of women.
Among 394 cases and 396 controls, women with at least 1 variant CYP2C9 allele had a significantly greater risk for adenoma (multivariate odds ratio [OR], 1.56; 95% confidence interval [CI], 1.13-2.15; P = 0.007). Although women who used aspirin regularly (>/=2 standard tablets/wk) experienced a lower risk for adenoma compared with non-regular users, the effect was similar irrespective of genotype. Women who smoked >20 pack-years had an OR of adenoma of 1.50 (95% CI, 1.07-2.12; P = 0.02) compared with those who smoked </=20 pack-years. Among women with at least 1 variant allele who smoked >20 pack-years, the OR of adenoma was 2.50 (95% CI, 1.44-4.38; P = 0.001) compared with women with no variant alleles who smoked </=20 pack-years.
Polymorphisms in the CYP2C9 enzyme are associated with elevated risk for colorectal adenoma. This observation does not appear to be related to modification of the effect of aspirin on adenoma risk, but may be associated with differential metabolism of environmental carcinogens.
长期服用阿司匹林与结直肠腺瘤风险降低相关，而吸烟会增加风险。细胞色素P-450（CYP）2C9（CYP2C9）酶参与多种药物的代谢，可能包括阿司匹林，以及诸如与吸烟相关的多环芳烃等致癌物。该酶的基因变异可能会调节阿司匹林和吸烟对腺瘤风险的影响。
在一项针对女性的前瞻性巢式病例对照研究中，我们根据CYP2C9基因型、阿司匹林使用情况和吸烟情况，研究了发生远端结直肠腺瘤的风险。
在394例病例和396例对照中，至少有1个CYP2C9变异等位基因的女性患腺瘤的风险显著更高（多变量优势比[OR]，1.56；95%置信区间[CI]，1.13 - 2.15；P = 0.007）。尽管与不经常服用阿司匹林的女性相比，经常服用阿司匹林（≥2标准片/周）的女性患腺瘤的风险较低，但无论基因型如何，这种效果相似。与吸烟≤20包年的女性相比，吸烟>20包年的女性患腺瘤的OR为1.50（95%CI，1.07 - 2.12；P = 0.02）。在至少有1个变异等位基因且吸烟>20包年的女性中，与吸烟≤20包年且无变异等位基因的女性相比，患腺瘤的OR为2.50（95%CI，1.44 - 4.38；P = 0.001）。
CYP2C9酶的多态性与结直肠腺瘤风险升高相关。这一观察结果似乎与阿司匹林对腺瘤风险的影响的改变无关，但可能与环境致癌物的差异代谢有关。
