期刊
HUMAN MOLECULAR GENETICS
卷 17, 期 23, 页码 3720-3727出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddn267
关键词
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资金
- Cancer Research UK
- Institute of Cancer Research
- European Union [LSHC-CT-2004-503465]
- Bobby Moore Fund
- CORE
- Thomas Falknor Fund
- St. George's Hospital Medical School
- Fondo de Investigacion Sanitaria [03/0070, 05/0071, 05/2031]
- Ministerio de Educacion y Ciencia [SAF 04-07190, 07-64873]
- Asociacion Espanola contra el Cancer
- Merck, Co
- Xunta de Galicia [PGI-DIT07PXIB9101209PR]
- Fundacion Olga Torres
- Fundacion de Investigacion Medica Mutua Madrilena
- Instituto de Salud Carlos III
- Ministerio de Sanidad
- FIS [051056, RD07/0064/0016]
- Instituto de Salud Carlos III, Madrid, Spain
- Academy of Finland
- Finnish Cancer Society
- Sigrid Juselius Foundation
- European Commission [9LSHG-CT2004-512142]
- Deutsche Krebshilfe
- German Ministry of Education and Research [01GS0426, 01GR0468]
- Medical Faculty, Kiel
- Federal Ministry of Education and Research [ZZ9603]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania. Leiden
- Dutch Cancer Society [UL2005-3247]
- Medical Ethical Committee [P01.019]
- Dutch Federation of Medical Sciences, Madrid
- Fondo Investigacion Sanitaria [PI070316, RD06/0020/0021]
- National Health and Medical Research Council (NHMRC) [209057, 251533, 396414]
- Cancer Council Victoria
- NHMRC Australia
- [GACR310/07/1430]
- MRC [G0301096] Funding Source: UKRI
- Medical Research Council [G0301096] Funding Source: researchfish
The common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy individuals. A significant association between the C allele of rs3802842 and CRC risk was found (per allele OR = 1.17; 95% confidence interval [CI]: 1.12-1.22; P = 1.08 x 10(-12)) with the risk allele more frequent in rectal than colonic disease (P = 0.02). In combination with 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 variants, the risk of CRC increases with an increasing numbers of variant alleles for the six loci (OR(per allele) = 1.19; 95% CI: 1.15-1.23; P(trend) = 7.4 x 10(-24)). Using the data from our genome-wide association study of CRC, LD mapping and imputation, we were able to refine the location of the causal locus to a 60 kb region and screened for coding changes. The absence of exonic mutations in any of the transcripts (FLJ45803, LOC120376, C11orf53 and POU2AF1) mapping to this region makes the association likely to be a consequence of non-coding effects on gene expression.
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