MMH/OGG1 is an 8‐hydroxyguanine‐specific DNA glycosylase/AP‐lyase, one of the mutator enzymes for the excision repair of 8‐hydroxyguanine. DNA polymorphisms in human MMH/OGG1 gene were newly identified and analyzed to examine a possible association with lung‐cancer risk by a population‐based study. Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266–7.845], indicating that the excision repair of 8‐hydroxyguanine may play a role in predisposition to lung cancer. Int. J. Cancer 80:18–21, 1999. © 1999 Wiley‐Liss, Inc.
Lung cancer is a leading and increasing cause of death by malignancy among men in Japan, also second-largest among women. Common genetic traits, such as those influencing detoxification or DNA repair, would be important determinants of population risk, though each of them might pose a low individual risk (Perera, 1997;Wei et al., 1996). 8-hydroxyguanine (8-OH-G, 7,8-dihydro-8-oxoguanine) is a major DNA oxidation product, and is implicated in mutagenesis induced by oxygen-radical-forming agents, including ionizing radiation and some chemical carcinogens, also believed to be involved in spontaneous mutation induced by metabolically produced oxygen radicals (Cheng et al., 1992;Shibutani et al., 1991;Wood et al., 1990). A mammalian 8-hydroxyguanine glycosylase/AP-lyase, a functional mutM homologue (MMH) has been identified as a homologue to yeast OGG1 protein (Aburatani et al., 1997;Arai et al., 1997;Bjoras et al., 1997;Lu et al., 1997;Radicella et al., 1997;Roldan-Arjona et al., 1997;Rosenquist et al., 1997). Defect in the repair of 8-OH-G might predispose such individuals to increased rate of somatic mutation under oxidative stress. In addition to MutM, MutY and MutT are other component enzymes involved in the repair of guanine oxidation (Cunningham, 1997), thus possibly involved in cancer risk. In this study, we first screened for variant alleles for the hMMH/OGG1 gene, then examined a possible association between hMMH/OGG1 polymorphism and lung-cancer risk in Japanese population. MATERIAL AND METHODS Genomic DNA preparationAll the patients and control cases were Japanese, collected with frequency matching for gender and age. Non-cancerous lung tissues were obtained from surgical specimens of lung-cancer cases at Tokyo Komagome Metropolitan Hospital, Tokyo, and Jichi Medical School Hospital, Tochigi, Japan. The cancers in this study were mostly non-small-cell lung carcinomas, since patient materials were collected through surgical resection. There were 76 cases of adenocarcinoma, 35 cases of squamous-cell carcinoma and 17 cases of other cell types. Control specimens were obtained with informed consent from healthy, unrelated individuals who visited a medical institution located in the same region (Tokyo area) for a general health check-up. Genomic DNA used for genotyping was extracted from non-cancerous tissues in cancer cases with standard procedures (Sambrook et al., 1989), and from peripheral-blood leukocytes in control cases using QIAamp blood kit (Qiagen, Chatsworth, CA). Among the 141 eligible cases and 304 eligible controls, we obtained adequate data from 128 lung-cancer cases and 268 controls. PCR-SSCPIndividual exon sequences were amplified by PCR, using primers in intron or non-coding regions (T.I., H.A.; data not shown) and used in single-strand-conformation-polymorphism (SSCP) analysis as described (Orita et al., 1989). Briefly, primers for exon 1, E1F (5Ј-ACGAGGCCTGGTTCTGGGTAG-3Ј) and E1R (5Ј-TTTGTACCCCATGCCAGGCAG-3Ј), were radio-labeled by [␥-32 P]ATP with T4 polynucleotide kinase, then used for amp...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.