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Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites.

Publication ,  Journal Article
Wang, L; Liu, H; Zhang, Z; Spitz, MR; Wei, Q
Published in: Cancer Epidemiol Biomarkers Prev
December 2006

O6-methylguanine, a methylated damage lesion in DNA, correlates with spontaneous G:C --> A:T transition mutations and leads to activation of oncogene K-ras or dysfunction of the tumor suppressor gene p53. O6-methylguanine-DNA methyltransferase (MGMT) is critical for repairing damage to the O6-position of guanine. Therefore, we tested our hypothesis that genetic variants of MGMT are associated with increased lung cancer risk in a Caucasian population of 1,121 lung cancer patients and 1,163 matched cancer-free controls. We genotyped four potentially functional single nucleotide polymorphisms (SNPs) of MGMT: exon 3 codon 84C --> T (L84F), exon 5 codon 143A --> G (I143V), and two promoter SNPs 135G --> T and 485C --> A. The allele frequency distributions of the SNPs of codon 84C --> T and the promoter 135G --> T in the cases were borderline different from that in the controls. After defining the minor allele (T for codon 84C --> T and G for codon 143A --> G) as the variant allele, we categorized the MGMT genotypes as either 0 variants (84CC-143AA) or 1-4 variants. Compared with 0 variants, those with 1-4 variants showed a statistically significantly increased risk of lung cancer (P = 0.040). Further stratification analysis showed that this increased risk was more pronounced in women, current smokers, and non-small cell lung cancer. We did not find any association between the MGMT promoter SNPs and lung cancer risk. Our findings suggest that non-synonymous SNPs in MGMT are associated with modestly increased risk of lung cancer in Caucasians and need to be further investigated.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

DOI

ISSN

1055-9965

Publication Date

December 2006

Volume

15

Issue

12

Start / End Page

2364 / 2369

Location

United States

Related Subject Headings

  • White People
  • Sequence Analysis, DNA
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • O(6)-Methylguanine-DNA Methyltransferase
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Humans
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, L., Liu, H., Zhang, Z., Spitz, M. R., & Wei, Q. (2006). Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev, 15(12), 2364–2369. https://doi.org/10.1158/1055-9965.EPI-06-0437
Wang, Luo, Hongji Liu, Zhengdong Zhang, Margaret R. Spitz, and Qingyi Wei. “Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites.Cancer Epidemiol Biomarkers Prev 15, no. 12 (December 2006): 2364–69. https://doi.org/10.1158/1055-9965.EPI-06-0437.
Wang L, Liu H, Zhang Z, Spitz MR, Wei Q. Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2364–9.
Wang, Luo, et al. “Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites.Cancer Epidemiol Biomarkers Prev, vol. 15, no. 12, Dec. 2006, pp. 2364–69. Pubmed, doi:10.1158/1055-9965.EPI-06-0437.
Wang L, Liu H, Zhang Z, Spitz MR, Wei Q. Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2364–2369.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

ISSN

1055-9965

Publication Date

December 2006

Volume

15

Issue

12

Start / End Page

2364 / 2369

Location

United States

Related Subject Headings

  • White People
  • Sequence Analysis, DNA
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • O(6)-Methylguanine-DNA Methyltransferase
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Humans
  • Genotype