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Novel O 6 ‐methylguanine‐DNA methyltransferase SNPs: A frequency comparison of patients with familial melanoma and healthy individuals in Sweden
Author(s) -
Egyházi S.,
Ma S.,
Smoczynski K.,
Hansson J.,
Platz A.,
Ringborg U.
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9078
Subject(s) - exon , single nucleotide polymorphism , biology , genetics , microbiology and biotechnology , promoter , melanoma , mutation , single strand conformation polymorphism , gene , guanine , cancer research , genotype , nucleotide , gene expression
The DNA repair protein O 6 ‐methylguanine‐DNA methyltransferase (MGMT) is involved in the cellular defense against alkylating agents. Genetic alterations in the MGMT gene may impair the protein's ability to remove alkyl groups from the O 6 ‐position of guanine, thereby raising the mutation rate and increasing the risk of cancer. We assessed polymorphisms in the promoter region and the 5 exons of the MGMT gene by PCR/SSCP and nucleotide sequence analysis of DNA extracted from blood samples. The population studied consisted of 89 melanoma patients, each belonging to a different family with a hereditary predisposition for melanoma, and 76 healthy individuals (blood donors). A total of 11 single nucleotide polymorphisms (SNPs) were detected, five in the promoter region, one in exon 1, two in exon 3 and three in exon 5. Six of the alterations were novel polymorphisms, of which five were located in the promoter region and one in exon 5. When the distribution of specific SNPs in cases and controls with only one variant was calculated; C575A was present only in melanoma patients (p=0.072). Moreover, while 20% of the healthy individuals had no SNPs this was the case in only 12.4% of the melanoma patients. However, no statistically significant differences were seen between cases and controls for any of the 11 SNPs. © 2002 Wiley‐Liss, Inc.