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hOGG1 polymorphism and loss of heterozygosity (LOH): Significance for lung cancer susceptibility in a caucasian population
Author(s) -
Wikman H.,
Risch A.,
Klimek F.,
Schmezer P.,
Spiegelhalder B.,
Dienemann H.,
Kayser K.,
Schulz V.,
Drings P.,
Bartsch H.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001215)88:6<932::aid-ijc15>3.0.co;2-p
Subject(s) - loss of heterozygosity , biology , genotype , allele , lung cancer , locus (genetics) , genetics , population , microbiology and biotechnology , minor allele frequency , allele frequency , gene , pathology , medicine , environmental health
Oxidative damage is implicated in several chronic diseases including cancer. 8‐Hydroxyguanine (8‐oxoG) is one of the major promutagenic DNA lesions, which is produced by reactive oxygen species, causes G:C to T:A transversions 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 sites in the human OGG1 gene, detected previously mainly in tumour tissue. The previously described Ser 326 Cys polymorphism was found to be common (allele frequency 0.22) in Caucasians. However, no major difference in Ser 326 Cys genotype distribution could be detected between cases and controls. Two 5`‐end polymorphisms previously found in Japanese as well as Arg 131 Gln could not be detected in this population. An Ala 85 Ser polymorphism was found in 2 controls, whereas Arg 46 Gln was detected in only 1 case. As the hOGG1 gene is mapped (3p26.2) to a region frequently lost in primary lung tumours, the frequency of loss of heterozygosity (LOH) was investigated. Forty‐three percent of the studied lung tumours exhibited loss of one of the hOGG1 alleles. The wt Ser 326 allele was not predominantly lost in our sample set, which suggests a minor role of this polymorphism in tumourgenesis. Our results show that LOH at the hOGG1 gene locus is a very common occurrence in lung tumourgenesis, possibly leading to increased mutational damage due to ROS in smokers. However, the hOGG1 polymorphisms studied are probably not major contributors to individual lung cancer susceptibility in Caucasians. Int. J. Cancer 88:932–937, 2000. © 2000 Wiley‐Liss, Inc.