Journal article
Characterization of 9p24 Risk Locus and Colorectal Adenoma and Cancer: Gene-Environment Interaction and Meta-Analysis
Cancer epidemiology, biomarkers & prevention, Vol.19(12), pp.3131-3139
12/01/2010
DOI: 10.1158/1055-9965.EPI-10-0878
PMCID: PMC3005543
PMID: 20978172
Abstract
Background: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.
Methods: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions.
Results: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01-1.40; P-trend = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99-1.25; P-trend = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03-1.12; P-trend = 0.001).
Conclusions: Our results suggest the A allele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies.
Impact: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. Cancer Epidemiol Biomarkers Prev; 19(12); 3131-9. (C) 2010 AACR.
Details
- Title: Subtitle
- Characterization of 9p24 Risk Locus and Colorectal Adenoma and Cancer: Gene-Environment Interaction and Meta-Analysis
- Creators
- Jonathan D. Kocarnik - Fred Hutch Cancer CenterCarolyn M. Hutter - Fred Hutch Cancer CenterMartha L. Slattery - University of UtahSonja I. Berndt - National Institutes of HealthLi Hsu - Fred Hutch Cancer CenterDavid J. Duggan - Translational Genomics Research InstituteJill Muehling - Translational Genomics Research InstituteBette J. Caan - Kaiser PermanenteShirley A. A. Beresford - University of WashingtonAleksandar Rajkovic - University of PittsburghGloria E. Sarto - University of Wisconsin School of Medicine and Public HealthJames R. Marshall - Roswell Park Cancer InstituteNazik Hammad - Queen's UniversityRobert B. Wallace - University of IowaKaren W. Makar - Fred Hutch Cancer CenterRoss L. Prentice - Fred Hutch Cancer CenterJohn D. Potter - Fred Hutch Cancer CenterRichard B. Hayes - New York UniversityUlrike Peters - Fred Hutch Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.19(12), pp.3131-3139
- DOI
- 10.1158/1055-9965.EPI-10-0878
- PMID
- 20978172
- PMCID
- PMC3005543
- NLM abbreviation
- Cancer Epidemiol Biomarkers Prev
- ISSN
- 1055-9965
- eISSN
- 1538-7755
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 9
- Grant note
- R01 CA059045; R01 CA120582 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01AG014358 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) N01WH032105; N01WH042120; N01WH042129; N01WH032122; N01WH032109; N01WH042110; N01WH042130; N01WH042131; N01WH042109; N01WH042132; N01WH032119; N01WH042126; N01WH042121; N01WH042114; N01WH042108; N01WH042107; N01WH042112; N01WH042116; N01WH032106; N01WH032112; N01WH022110; N01WH032115; N01WH042111; N01WH042123; N01WH042122; N01WH032108; N01WH042117; N01WH042115; N01WH042125; N01WH042119; N01WH032100; N01WH032111; N01WH032113; N01WH032102; N01WH042113; N01WH032118 / WOMEN'S HEALTH INITIATIVE - OFFICE OF THE DIRECTOR NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Division of Cancer Epidemiology and Genetics; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics R01CA120582; P01CA053996; R01CA059045; R25CA094880; K22CA118421; U01CA137088; R01CA048998 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIH R01 CA120582; NIH K22 CA118421; NIH R01 CA48998; NIH R01 CA059045; NIH R25 CA094880; NIH R01 AG14358; PO1 CA53996 / National Cancer Institute (NCI), National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) N01WH22110; 24152; 32100-2; 32105-6; 32108-9; 32111-13; 32115; 32118-32119; 32122; 42107-26; 42129-32; 44221 / National Heart, Lung, and Blood Institute, NIH, DHHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363594702771
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