Bock C H, Wenzlaff A S, Cote M L, Land S J, Schwartz A G
Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Carcinogenesis. 2005 Feb;26(2):381-6. doi: 10.1093/carcin/bgh314. Epub 2004 Oct 21.
The NAD(P)H:quinone oxidoreductase 1 gene, NQO1, contains a C to T transition at amino acid codon 187, which results in very low enzymatic activity. Previous studies of the association between NQO1 genotype and lung cancer have had mixed findings. This population-based case control study examines the association between NQO1 genotype and lung cancer in the largest sample of never smokers (<100 cigarettes, lifetime) to date. Cases (n = 161) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program, and 5-year age- and race-matched population-based controls (n = 173) were identified using random digit dialing. Allele frequencies of C and T, respectively, were 0.79 and 0.21 in Caucasians, and 0.84 and 0.16 in African Americans. Among those diagnosed aged >/=50 years, C/T and T/T genotyped individuals had 0.48 times lower lung cancer risk than individuals with C/C genotype (95% CI: 0.27-0.87). There was a non-significant suggestion of a protective effect associated with the T allele among those with a history of environmental tobacco smoke exposure (OR = 0.57, 95% CI: 0.32-1.03) but not among those without (OR = 0.98, 95% CI: 0.41-2.38). Sex, race, family history of lung cancer and histologic type did not modify the effect of NQO1 genotype on lung cancer risk. The observed risk reductions may be attributable to the greatly reduced procarcinogen activating of NAD(P)H:quinone oxidoreductase 1 in individuals with at least one copy of the T allele.
烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）：醌氧化还原酶1基因（NQO1）在氨基酸密码子187处存在一个从C到T的转换，这导致酶活性极低。先前关于NQO1基因型与肺癌之间关联的研究结果不一。这项基于人群的病例对照研究在迄今为止最大规模的从不吸烟者（终生吸烟量<100支）样本中，考察了NQO1基因型与肺癌之间的关联。通过底特律大都市监测、流行病学和最终结果（SEER）项目确定了病例（n = 161），并使用随机数字拨号法确定了5年年龄和种族匹配的基于人群的对照（n = 173）。在白种人中，C和T等位基因频率分别为0.79和0.21，在非裔美国人中分别为0.84和0.16。在年龄≥50岁被诊断出的人群中，C/T和T/T基因型个体患肺癌的风险比C/C基因型个体低0.48倍（95%置信区间：0.27 - 0.87）。在有环境烟草烟雾暴露史的人群中，有与T等位基因相关的保护作用的非显著提示（比值比=0.57，95%置信区间：0.32 - 1.03），但在无此暴露史的人群中则没有（比值比=0.98，95%置信区间：0.41 - 2.38）。性别、种族、肺癌家族史和组织学类型并未改变NQO1基因型对肺癌风险的影响。观察到的风险降低可能归因于至少有一个T等位基因拷贝的个体中NAD(P)H：醌氧化还原酶1的前致癌物激活作用大大降低。
