Meta Association of Colorectal Cancer Confirms Risk Alleles at 8q24 and 18q21

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 18; no. 2; pp. 616 - 621
• Main Authors: Curtin, Karen, Lin, Wei-Yu, George, Rina, Katory, Mark, Shorto, Jennifer, Cannon-Albright, Lisa A., Bishop, D. Timothy, Cox, Angela, Camp, Nicola J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.02.2009
• Subjects: 18q21; 8q24; 9p24; Aged; Alleles; Biological and medical sciences; case-control; Case-Control Studies; Chi-Square Distribution; Chromosomes, Human, Pair 18 - genetics; Chromosomes, Human, Pair 8 - genetics; colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; family resource; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Medical sciences; meta association; Middle Aged; Monte Carlo Method; Polymorphism, Single Nucleotide; Risk Factors; SMAD7; Software; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; United Kingdom - epidemiology; Utah - epidemiology; Genetic mapping; Rectal disease; Colorectal cancer; Risk; Malignant tumor; Chromosome C8; Colonic disease; Allele; Chromosome E18; Association; Cancerology; Risk factor; Digestive diseases; Intestinal disease; Genetics; Cancer
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0690

Background: Genome-wide association studies of colorectal cancer (CRC) have identified genetic variants that reproducibly associate with CRC. Associations of 12 single nucleotide polymorphisms at 8q24, 9p24, and 18q21 ( SMAD7 ) and CRC were investigated in a three-center collaborative study including two U.K. case-control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases from high-risk Utah pedigrees. Methods: Our combined resource included 1,092 CRC case subjects and 1,060 age- and sex-matched controls. Meta statistics and Monte Carlo significance testing using Genie software provided a valid combined analysis of our mixed independent and related case-control resource. We also evaluated whether these associations differed by sex, age at diagnosis, family history, or tumor site. Results: At 8q24, we observed two independent significant associations at single nucleotide polymorphisms located in two different risk regions of 8q24: rs6983267 in region 3 [ P trend = 0.01; per allele odds ratio (OR), 1.17; 95% confidence intervals (95% CI), 1.03-1.32] and rs10090154 in region 5 ( P trend = 0.05; per allele OR, 1.24; 95% CI, 1.01-1.51). At 18q21, associations were observed in distal colon tumors but not in proximal or rectal cancers: rs4939827 ( P trend = 0.007; per allele OR, 0.77; 95% CI, 0.64-0.93; case-case p diff = 0.03) and rs12953717 ( P trend = 0.01; per allele OR, 1.27; 95% CI, 1.06-1.52). We were unable to detect any associations at 9p24 with CRC. Conclusions: Our investigation confirms that variants across multiple risk regions of 8q24 are associated with CRC, and that associations at 18q21 differ by tumor site. (Cancer Epidemiol Biomarkers Prev 2009;18(2):616–21)