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PMID: 17898541 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.

Human heredity ·Vol. 65 ·No. 2 ·2008-00-00 ·Pages 105-18

Andrew AS, Karagas MR, Nelson HH, Guarrera S, Polidoro S, Gamberini S, Sacerdote C, Moore JH, Kelsey KT, Demidenko E, Vineis P, Matullo G

Abstract

A number of common non-synonymous single nucleotide polymorphisms (SNPs) in DNA repair genes have been reported to modify bladder cancer risk. These include: APE1-Asn148Gln, XRCC1-Arg399Gln and XRCC1-Arg194Trp in the BER pathway, XPD-Gln751Lys in the NER pathway and XRCC3-Thr241Met in the DSB repair pathway. To examine the independent and interacting effects of these SNPs in a large study group, we analyzed these genotypes in 1,029 cases and 1,281 controls enrolled in two case-control studies of incident bladder cancer, one conducted in New Hampshire, USA and the other in Turin, Italy. The odds ratio among current smokers with the variant XRCC3-241 (TT) genotype was 1.7 (95% CI 1.0-2.7) compared to wild-type. We evaluated gene-environment and gene-gene interactions using four analytic approaches: logistic regression, Multifactor Dimensionality Reduction (MDR), hierarchical interaction graphs, classification and regression trees (CART), and logic regression analyses. All five methods supported a gene-gene interaction between XRCC1-399/XRCC3-241 (p = 0.001) (adjusted OR for XRCC1-399 GG, XRCC3-241 TT vs. wild-type 2.0 (95% CI 1.4-3.0)). Three methods predicted an interaction between XRCC1-399/XPD-751 (p = 0.008) (adjusted OR for XRCC1-399 GA or AA, XRCC3-241 AA vs. wild-type 1.4 (95% CI 1.1-2.0)). These results support the hypothesis that common polymorphisms in DNA repair genes modify bladder cancer risk and highlight the value of using multiple complementary analytic approaches to identify multi-factor interactions.

MeSH Terms
Adult Aged DNA Repair/genetics Factor Analysis, Statistical Humans Informed Consent Interviews as Topic Italy Middle Aged Models, Genetic New Hampshire/epidemiology Polymorphism, Genetic Registries Regression Analysis Risk Factors Urinary Bladder Neoplasms/epidemiology,genetics
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Andrew Angeline S
Department of Community and Family Medicine, Section of Biostatistics and Epidemiology, Dartmouth Medical School, Lebanon, NH 03756, USA. Angeline.Andrew@dartmouth.edu
Karagas Margaret R
Nelson Heather H
Guarrera Simonetta
Polidoro Silvia
Gamberini Sara
Sacerdote Carlotta
Moore Jason H
Kelsey Karl T
Demidenko Eugene
Vineis Paolo
Matullo Giuseppe
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Article Info
Journal
Human heredity
Abbr.
Hum Hered
ISSN
1423-0062
DOI
10.1159/000108942
Email
angeline.andrew@dartmouth.edu
Published
2008-00-00
Epub
2007-00-26
Pages
105-18
Language
English
Region
Switzerland
NLM ID
0200525
PMCID
PMC2857629
Subset
IM
Grants
NCI NIH HHS · R01 CA057494 · United States
NIEHS NIH HHS · ES00002 · United States
NIEHS NIH HHS · ES07373 · United States
NIEHS NIH HHS · 5 P42 ES05947 · United States
NCI NIH HHS · CA82354 · United States
NIEHS NIH HHS · P30 ES000002 · United States
NIEHS NIH HHS · P42 ES007373 · United States
NCRR NIH HHS · P20 RR018787 · United States
NCI NIH HHS · R03 CA099500 · United States
NCI NIH HHS · CA102327 · United States
NCI NIH HHS · P30 CA023108 · United States
NCRR NIH HHS · RR018787 · United States
NCI NIH HHS · CA57494 · United States
NIEHS NIH HHS · P42 ES005947 · United States
NCI NIH HHS · K07 CA102327 · United States
NCI NIH HHS · CA099500 · United States
NCI NIH HHS · R01 CA082354 · United States
External Links
PubMed source DOI: 10.1159/000108942 PMC Full Text View journal details
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