Tuberc Respir Dis.  2006 Sep;61(3):248-255. 10.4046/trd.2006.61.3.248.

Promoter Polymorphism of RRM1 Gene in Korean Lung Cancer Population

• Ko KH
• Kim EJ
• Oh IJ
• Kim SO
• Son JG
• Jung JP
• Cho GJ
• Ju JY
• Kim KS
• Kim YI
• Lim SC
• Kim YC
• Bepler G

• KMID: 1970264
• DOI: http://doi.org/10.4046/trd.2006.61.3.248

Abstract

BACKGROUND: LOH11A is a region with frequent allele loss (>75%) in lung cancer that is located on the centromeric part of chromosome 11p15.5. Clinical and cell biological studies suggest that this region contains a gene associated with metastatic tumor spread. RRM1 encoding the M1 subunit of ribonucleotide reductase, which is an enzyme that catalyses the rate-limiting step in deoxyribonucleotide synthesis, is located in the LOH11A region.
METHODS
Polymorphisms were found at nucleotide position (-)37 (C/A) and (-)524 (C/T) from the beginning of exon 1 of the RRM1 gene that might regulate the expression of RRM1. We studied the polymorphisms in 127 Korean individuals (66 lung cancer and 61 normal controls) and compared with those of 140 American patients with lung cancer.
RESULTS
CC, AC and AA were found at the (-)37 position in 64(50.4%), 55(43.3%), and 8(6.3%) out of 127 Korean individuals (66 cancer, 61 non-cancer patients), respectively. There was a similar frequency of allele A at (-)37 in the American(27.9%) and Korean population(28.0%). CC, CT and TT was found at the (-)524 position in 24(18.9%), 44(34.6%), and 59(46.5%) out of the 127 Korean individuals, respectively. There was a similar frequency of allele C at (-)524 in the American(34.6%) and Korean population(36.2%).There was no difference in the frequency of the (-)37 and (-)524 genotypes between the cancer and non-cancer group. However there was a significant correlation of the genotypes between (-)37 and (-)524 (p<0.001), which suggests the possible coordination of these polymorphisms in the regulation of the promoter activity of the RRM1 gene.
CONCLUSION
RRM1 promoter polymorphisms were not found to be significant risk factors for lung cancer. However, a further study of the promoter activity and expression of the RRM1 gene according to the pattern of the polymorphism will be needed.

Keyword

RRM1 gene; Promoter polymorphism; Lung cancer; Korean

MeSH Terms

Alleles
Catalysis
Exons
Genes, vif
Genotype
Humans
Lung Neoplasms*
Lung*
Ribonucleotide Reductases
Risk Factors
Ribonucleotide Reductases

Figure

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  Figure 1 Allelotyping of RRM1 (-)37 C/A polymorphism. Restriction enzyme BbSI cuts when (-)37 base is A. Homozygous A allelotype (lane 3 from left) shows complete digestion into 157 bp bands. Homozygous C allelotype (lane 4 and 7) have original 217 bp bands only without digestion.

• 

  Figure 2 Allelotyping of RRM1 (-)524 C/A polymorphism. Restriction enzyme ApoI cuts when (-)524 base is T. Homozygous T allelotype (lane 2, 5 and 6 from left) shows complete digestion into 74 bp bands. Homozygous C allelotype (lane 3 and 4) have original 176 bp bands only without digestion.

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