In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. LB-411-LB-411
Abstract:
The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. Pancreatic carcinoma represents the fourth leading cause of cancer-related deaths in the country, with a minimum of patients surviving 5 years. The etiology and molecular pathogenesis of above cancers are weakly understood. TP53 plays a role in cell cycle and apoptosis and is frequently mutated in solid tumors, including colorectal and pancreatic. Assuming that genetic variation may affect susceptibility to cancer development, the role of polymorphisms and haplotypes of TP53, CDKN1A and CDKN2A in modulating the cancer risk was addressed. We investigated selected polymorphisms in TP53 (rs17878362:A1 & gt;A2, rs1042522:G & gt;C, rs12947788:C & gt;T, and rs17884306:G & gt;A), CDKN1A (rs1801270:C & gt;A and rs1059234:C & gt;T), and CDKN2A (rs3731249:G & gt;A, rs11515:C & gt;G, and rs3088440:C & gt;T) genes in 614 hospital-based cases and 614 matched controls from the country for association with colorectal cancer and 240 cases and controls (for a total of 1827 individuals) for association with pancreatic cancer risk. For CRC, none of the studied polymorphisms was strongly associated with risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P & lt;0.0001). In comparison to the most common haplotype (A1GCG), the haplotype A2CCG was associated with an increased risk (OR 1.40, 95% CI 1.07-1.82), while four other less frequent haplotypes A1CCG, A2GCG A1GTG, and A1GCA were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon and rectal cancers. No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. For pancreatic cancer: carriers of the variant C allele of rs1042522 polymorphism were at an increased risk of (OR 1.73; 95% CI 1.26-2.39; p=0.001). The A2CCG haplotype in comparison with the most common haplotype (A1GCG) was associated with an increased risk (OR 1.39; 95% CI 1.02-1.88; p=0.034), and the A1CCG with a reduced risk (OR 0.30; 95% CI 0.12 -0.76; p=0.011) for this cancer. Genetic variation in TP53 may contribute, alone or in concert with other risk factors, to modify the inherited susceptibility to both colorectal and pancreatic cancers, as well as to other gastrointestinal cancers. Supported by GACR 310/07/1430. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-411.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-LB-411
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
Permalink