DNA repair gene variants in relation to overall cancer risk: a population-based study

被引:20
|
作者
Alberg, Anthony J. [1 ,2 ]
Jorgensen, Timothy J. [3 ]
Ruczinski, Ingo [4 ]
Wheless, Lee [1 ,2 ]
Shugart, Yin Yao [5 ]
Berthier-Schaad, Yvette [6 ,7 ]
Kessing, Bailey [7 ]
Hoffman-Bolton, Judith [6 ,8 ]
Helzlsouer, Kathy J. [9 ]
Kao, W. H. Linda [6 ]
Francis, Lesley [1 ,2 ]
Alani, Rhoda M. [10 ]
Smith, Michael W. [11 ]
Strickland, Paul T. [6 ,12 ]
机构
[1] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA
[2] Med Univ S Carolina, Div Epidemiol & Biostat, Dept Med, Charleston, SC 29425 USA
[3] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA
[4] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA
[5] NIMH, Div Intramural Res Program, Rockville, MD 20857 USA
[6] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
[7] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA
[8] George W Comstock Ctr Publ Hlth Res & Prevent, Washington Cty, DC USA
[9] Mercy Med Ctr, Prevent Res Ctr, Baltimore, MD USA
[10] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA
[11] SAIC Frederick Inc, NCI Frederick, Adv Technol Program, Genet & Genom Grp, Frederick, MD USA
[12] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA
关键词
O-6-METHYLGUANINE-DNA METHYLTRANSFERASE MGMT; NONMELANOMA SKIN-CANCER; PROMOTER METHYLATION; SUSCEPTIBILITY; HYPERMETHYLATION; POLYMORPHISMS; ASSOCIATION; DAMAGE; FALSE;
D O I
10.1093/carcin/bgs304
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ascertained through 2007 compared with a sample of 2296 with no cancer. Associations were measured between 759 DNA repair gene single nucleotide polymorphisms (SNPs) and risk of all cancers. A SNP in O-6-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.191.43 and P-value: 4.1 10(8)]. The association between rs2296675 and cancer risk was stronger among those aged 54 years old than those who were epsilon 55 years at baseline (P-for-(interaction) 0.021). OR were in the direction of increased risk for all 15 categories of malignancies studied (P < 0.0001), ranging from 1.22 (P 0.42) for ovarian cancer to 2.01 (P 0.008) for urinary tract cancers; the smallest P-value was for breast cancer (OR 1.45, P 0.0002). The results indicate that the minor allele of MGMT SNP rs2296675, a common genetic marker with 37% carriers, was significantly associated with increased risk of cancer across multiple tissues. Replication is needed to more definitively determine the scientific and public health significance of this observed association.
引用
收藏
页码:86 / 92
页数:7
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