hOGG1 polymorphism and loss of heterozygosity (LOH): Significance for lungcancer susceptibility in a Caucasian population

Oxidative damage is implicated in several chronic diseases including cancer . 8-Hydroxyguanine (8-oxoG) is one of the major promutagenic DNA lesions, w hich is produced by reactive oxygen species, causes G:C to T:A transversion s and is excised by OGG1, an 8-oxoG specific DNA glycosylase/ AP-Lyase. In a nested case-control study, gDNA from 105 Caucasian primary non-small cell lung cancer cases and 105 matched controls was screened for 6 possible new polymorphic rites in the human OGG1 gene, detected previously mainly in tu mour tissue. The previously described Ser(326)Cys polymorphism was found to be common (allele frequency 0.22) in Caucasians. However, no major differe nce in Ser(326)Cys genotype distribution could be detected between cases an d controls. Two 5'-end polymorphisms previously found in Japanese as well a s Arg(13) Gin could not be detected in this population. An Ala(85)Ser polym orphism was found in 2 controls, whereas Arg(46)Gln was detected in only I case. As the hOGG1 gene is mapped (3p26.2) to a region frequently lost in p rimary lung tumours, the frequency of loss of heterozygosity (LOH) was inve stigated. Forty-three percent of the studied lung tumours exhibited loss of one of the hOGG1 alleles. The wt Ser(326) allele was not predominantly los t in our sample set, which suggests a minor role of this polymorphism in tu mourgenesis. Our results show that LOH at the hOGG1 gene locus is a very co mmon occurrence in lung tumourgenesis, possibly leading to increased mutati onal damage due to ROS in smokers. However, the hOGG1 polymorphisms studied are probably not major contributors to individual lung cancer susceptibili ty in Caucasians. Int J. Cancer 88:932-937, 2000. (C) 2000 Wiley-Liss, Inc.