In:
Human Heredity, S. Karger AG, Vol. 65, No. 2 ( 2008), p. 105-118
Abstract:
〈 i 〉 Objectives: 〈 /i 〉 A number of common non-synonymous single nucleotide polymorphisms (SNPs) in DNA repair genes have been reported to modify bladder cancer risk. These include: 〈 i 〉 APE1- 〈 /i 〉 Asn148Gln, 〈 i 〉 XRCC1- 〈 /i 〉 Arg399Gln and 〈 i 〉 XRCC1- 〈 /i 〉 Arg194Trp in the BER pathway, 〈 i 〉 XPD- 〈 /i 〉 Gln751Lys in the NER pathway and 〈 i 〉 XRCC3- 〈 /i 〉 Thr241Met in the DSB repair pathway. 〈 i 〉 Methods: 〈 /i 〉 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. 〈 i 〉 Results: 〈 /i 〉 The odds ratio among current smokers with the variant 〈 i 〉 XRCC3- 〈 /i 〉 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 〈 i 〉 XRCC1- 〈 /i 〉 399/ 〈 i 〉 XRCC3- 〈 /i 〉 241 (p = 0.001) (adjusted OR for 〈 i 〉 XRCC1- 〈 /i 〉 399 GG, 〈 i 〉 XRCC3- 〈 /i 〉 241 TT vs. wild-type 2.0 (95% CI 1.4–3.0)). Three methods predicted an interaction between 〈 i 〉 XRCC1- 〈 /i 〉 399/ 〈 i 〉 XPD- 〈 /i 〉 751 (p = 0.008) (adjusted OR for 〈 i 〉 XRCC1- 〈 /i 〉 399 GA or AA, 〈 i 〉 XRCC3- 〈 /i 〉 241 AA vs. wild-type 1.4 (95% CI 1.1–2.0)). 〈 i 〉 Conclusions: 〈 /i 〉 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.
Type of Medium:
Online Resource
ISSN:
0001-5652
,
1423-0062
Language:
English
Publisher:
S. Karger AG
Publication Date:
2008
detail.hit.zdb_id:
1482710-4
SSG:
12
Permalink
