Pierce L M, Sivaraman L, Chang W, Lum A, Donlon T, Seifried A, Wilkens L R, Lau A F, Le Marchand L
Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1199-204.
Tobacco smoking is a strong cause of lung cancer. However, because only a small proportion of smokers develop the disease, other factors, including genetic susceptibility, may be important in determining lung cancer risk. Polymorphisms in the TP53 tumor suppressor gene and HRAS1 proto-oncogene have been associated in some studies with this cancer; we sought to replicate these associations in an ethnically diverse population in Hawaii. We conducted a population-based case-control study among 334 incident lung cancer cases and 446 controls of Caucasian, Japanese, or Native Hawaiian origin. In-person interviews collected detailed information on lifestyle risk factors. DNA was extracted from peripheral blood leukocytes, and genotyping was performed using a PCR-based assay for the TP53 codon 72 polymorphism and Southern blot analysis and PCR for allelic polymorphisms in the HRAS1 minisatellite. Logistic regression analyses were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for smoking and other risk factors. The presence of two rare HRAS1 alleles was associated with a 2.2-fold (95% CI, 1.0-5.0) increased lung cancer risk for all ethnic groups combined. The association was present in Native Hawaiians (OR, 5.2; 95% CI, 1.1-24.4) and was suggested for Japanese (OR, 2.8; 95% CI, 0.6-12.5); no association was observed in Caucasians (OR, 0.8; 95% CI, 0.2-3.6). This association was also observed for each lung cancer cell type. The presence of only one rare allele did not increase risk for any ethnic group or cell type. No significant association was found between the TP53 codon 72 polymorphism and lung cancer [OR, 1.4 (95% CI, 0.8-2.4) for the Pro/Pro genotype compared with the Arg/Arg genotype]. This study suggests that the presence of two rare HRAS1 alleles confers an increased lung cancer risk in Native Hawaiians and Japanese but possibly not in Caucasians. The amino acid replacement of arginine by proline at codon 72 of TP53 appears not to be important in determining lung cancer risk in this population.
吸烟是导致肺癌的一个重要原因。然而，由于只有一小部分吸烟者会患上这种疾病，所以其他因素，包括遗传易感性，在决定肺癌风险方面可能也很重要。在一些研究中，TP53肿瘤抑制基因和HRAS1原癌基因的多态性与这种癌症有关联；我们试图在夏威夷一个种族多样化的人群中重现这些关联。我们在334例新诊断的肺癌病例和446名白种人、日本人或夏威夷原住民对照中开展了一项基于人群的病例对照研究。通过面对面访谈收集了关于生活方式风险因素的详细信息。从外周血白细胞中提取DNA，并使用基于PCR的方法对TP53密码子72多态性进行基因分型，以及使用Southern印迹分析和PCR对HRAS1微卫星中的等位基因多态性进行分析。采用逻辑回归分析来计算调整吸烟和其他风险因素后的比值比（OR）和95%置信区间（CI）。所有种族群体中，两种罕见的HRAS1等位基因的存在与肺癌风险增加2.2倍（95%CI，1.0 - 5.0）相关。这种关联在夏威夷原住民中存在（OR，5.2；95%CI，1.1 - 24.4），在日本人中也有提示（OR，2.8；95%CI，0.6 - 12.5）；在白种人中未观察到关联（OR，0.8；95%CI，0.2 - 3.6）。在每种肺癌细胞类型中也观察到了这种关联。仅存在一个罕见等位基因并未增加任何种族群体或细胞类型的风险。在TP53密码子72多态性与肺癌之间未发现显著关联[与Arg/Arg基因型相比，Pro/Pro基因型的OR为1.4（95%CI，0.8 - 2.4）]。这项研究表明，两种罕见的HRAS1等位基因的存在会增加夏威夷原住民和日本人患肺癌的风险，但对白种人可能并非如此。在该人群中，TP53密码子72处脯氨酸取代精氨酸的氨基酸替换似乎在决定肺癌风险方面并不重要。
