In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4722-4722
Abstract:
Background: Endometrial cancer genetic susceptibility studies have largely focused on genes in the sex steroid hormone, checkpoint, and cell-cycle pathways, but single nucleotide polymorphisms (SNPs) in genes involved in other cancer-related pathways might also influence risk. Methods: We investigated the association between endometrial cancer risk and ∼29,000 SNPs in over 1,300 cancer-related candidate genes in the inflammation, metabolism, and other carcinogenic pathways in the Polish Endometrial Cancer Study (PECS), a population-based investigation involving 417 cases and 407 controls. TagSNPs were located in the respective gene or within 10 kb or 5 kb downstream; had a minor allele frequency (MAF) & gt;5% in various ethnic groups; and were not represented by a current tag SNP in linkage disequilibrium (LD; r2 & gt;0.80). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age (5-year categories). The most significant finding was followed up in the Australian National Endometrial Cancer Study (ANECS), a population-based case-control study of 815 cases and 822 controls. Results: In PECS, we found three SNPs in two loci associated with endometrial cancer risk at P & lt;0.0001. Two highly correlated SNPs in IQGAP1, rs2601207 (OR = 0.65; 95% CI: 0.53 - 0.81, P trend = 6.0 × 10−5) and rs6496677 (0.66; 0.54 - 0.81, P trend = 8.0 × 10−5), were associated with a decreased risk. In addition, a variant in UBE3A, rs4445877, was associated with increased risk (1.53; 1.24 - 1.90, P trend = 9.0 × 10−5). We followed up the rs2601207 association in ANECS and observed a non-significantly decreased risk (0.90; 0.77 - 1.05, P trend = 0.18). The pooled per allele OR was 0.81 (95% CI: 0.72 - 0.92), P trend = 0.001); however, there was evidence for heterogeneity by study (P-heterogeneity = 0.01). Conclusion: Data from PECS suggests associations between endometrial cancer risk and variants in IQGAP1, a gene that is a key mediator in several cellular processes related to carcinogenesis, and UBE3A, encoding ubiquitin protein ligase 3A involved in the degradation of cancer-associated proteins such TP53. The association with IQGAP1 was not confirmed in a larger study population; and further studies are needed to follow up other potential associations between endometrial cancer risk and cancer candidate genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4722.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-4722
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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