TY - JOUR
T1 - DNA repair gene variants in relation to overall cancer risk
T2 - A population-based study
AU - Alberg, Anthony J.
AU - Jorgensen, Timothy J.
AU - Ruczinski, Ingo
AU - Wheless, Lee
AU - Shugart, Yin Yao
AU - Berthier-Schaad, Yvette
AU - Kessing, Bailey
AU - Hoffman-Bolton, Judith
AU - Helzlsouer, Kathy J.
AU - Linda Kao, W. H.
AU - Francis, Lesley
AU - Alani, Rhoda M.
AU - Smith, Michael W.
AU - Strickland, Paul T.
N1 - Funding Information:
US National Cancer Institute (R01 CA105069, HHSN26120080001E) and the Intramural Research Program of the NCI, Center for Cancer Research. This publication does not necessarily reflect the views or policies of the National Cancer Institute, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, the US government, or the Maryland Cancer Registry, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
Funding Information:
Cancer incidence data were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, which is funded by the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/1
Y1 - 2013/1
N2 - 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 O6-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.19-1.43 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 ≥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.
AB - 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 O6-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.19-1.43 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 ≥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.
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U2 - 10.1093/carcin/bgs304
DO - 10.1093/carcin/bgs304
M3 - Article
C2 - 23027618
AN - SCOPUS:84872168297
VL - 34
SP - 86
EP - 92
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 1
ER -