TY - JOUR
T1 - Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic whites
AU - Wang, Luo
AU - Liu, Hongji
AU - Zhang, Zhengdong
AU - Spitz, Margaret R.
AU - Wei, Qingyi
PY - 2006/12
Y1 - 2006/12
N2 - 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. O 6-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 O variants (84CC-143AA) or 1-4 variants. Compared with O 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.
AB - 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. O 6-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 O variants (84CC-143AA) or 1-4 variants. Compared with O 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.
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U2 - 10.1158/1055-9965.EPI-06-0437
DO - 10.1158/1055-9965.EPI-06-0437
M3 - Article
C2 - 17164358
AN - SCOPUS:33846105279
SN - 1055-9965
VL - 15
SP - 2364
EP - 2369
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 12
ER -