Wrensch Margaret R, Miike Rei, Sison Jennette D, Kelsey Karl T, Liu Mei, McMillan Alex, Quesenberry Charles, Wiencke John K
Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
Int J Cancer. 2005 Jan 1;113(1):141-7. doi: 10.1002/ijc.20537.
We examined CYP1A1 T6235C (M1) and A4889G (M2) polymorphisms in San Francisco Bay Area African Americans and Latinos who were newly diagnosed with primary lung cancer from September 1998 to November 2002 and in age-gender-ethnicity frequency-matched controls. Owing mainly to rapid mortality of cases, overall percentages of cases genotyped were 26% and 32% for Latinos and African Americans, respectively. CYP1A1 variants were genotyped for Latinos (104 cases, 278 controls) and African Americans (226 cases, 551 controls). M1 and M2 frequencies in controls were 0.23 and 0.02 for African Americans and 0.38 and 0.29 for Latinos. In Latinos, the overall inverse odds ratio (OR) of 0.51 (95% CI = 0.32-0.81) for M1 variant genotype resulted from an inverse interaction with smoking. Nonsmokers with M1 genotype had a slight elevated OR (1.5; 0.59-3.7), but those with less than 30 or 30 or more pack-year history had 0.20 (0.06-0.70) and 0.21 (0.06-0.81) times (about 1/5) the odds expected if smoking and genotype were independent lung cancer risk factors. African Americans had interactions of similar magnitude that were not statistically significant. Results for M2 were very similar. Inverse interactions of CYP1A1 variants and smoking-associated lung cancer risk in Latinos might be causal, due to undetected bias or confounding, or represent a unique linkage disequilibrium between a new lung cancer locus and CYP1A1 in this highly admixed population.
我们检测了1998年9月至2002年11月新诊断为原发性肺癌的旧金山湾区非裔美国人和拉丁裔人群以及年龄、性别、种族频率匹配的对照组中CYP1A1基因T6235C(M1)和A4889G(M2)多态性。主要由于病例的快速死亡,拉丁裔和非裔美国人的基因分型病例总体百分比分别为26%和32%。对拉丁裔(104例病例,278例对照)和非裔美国人(226例病例,551例对照)进行了CYP1A1变异基因分型。非裔美国人对照组中M1和M2频率分别为0.23和0.02,拉丁裔分别为0.38和0.29。在拉丁裔中,M1变异基因型的总体逆比值比(OR)为0.51(95%CI = 0.32 - 0.81),这是由与吸烟的反向相互作用导致的。M1基因型的非吸烟者OR略有升高(1.5;0.59 - 3.7),但吸烟史少于30包年或30包年及以上者的OR分别为预期值的0.20(0.06 - 0.70)倍和0.21(0.06 - 0.81)倍(约为1/5),前提是吸烟和基因型是独立的肺癌危险因素。非裔美国人有类似程度的相互作用,但无统计学意义。M2的结果非常相似。拉丁裔中CYP1A1变异与吸烟相关肺癌风险的反向相互作用可能是因果关系,可能是由于未检测到的偏倚或混杂因素,或者代表了这个高度混合人群中新的肺癌基因座与CYP1A1之间独特的连锁不平衡。