title: Association of genetic variants at 8q24 with breast cancer risk.
abstract: Recent whole genome association studies of prostate, breast, and colorectal cancer have identified susceptibility loci on 8q24. We genotyped three variants associated with prostate cancer (rs10090154, rs13254738, and rs7000448), one associated with both prostate and colorectal cancer (rs6983267), and one associated with breast cancer (rs13281615) in a series of 1,499 breast cancer cases and 1,390 controls. 1,267 (85%) of the cases had two primary breast cancers. Our analysis provides further evidence of the relationship between rs13281615 and risk of breast cancer, with heterozygote odds ratio (OR) 1.30 95% confidence interval (CI) 1.09-1.54 and homozygote OR 1.52 (95% CI, 1.22-1.89; P trend = 0.00003), and confirms the prediction that the risk is substantially higher in this genetically enriched series (OR per allele, 1.24; 95% CI, 1.12-1.38) than in a large series of mainly unselected cases (reported OR per allele, 1.08; 95% CI, 1.05-1.11). We observed a protective effect of rs13254738 for breast cancer (allelic OR, 0.88; 95% CI, 0.78-0.98; P = 0.02), which is supported by the Cancer Genetic Markers of Susceptibility data (pooled allelic OR, 0.88; 95% CI, 0.81-0.96; P = 0.003). None of the other three single nucleotide polymorphisms, two associated with prostate (rs10090154 and rs7000448) and one with both prostate and colorectal cancers (rs6583267), was associated with breast cancer risk in our study. This evidence of a protective effect for breast cancer of one variant (rs13254738) that has been associated previously with a 1.25-fold increased risk of prostate cancer, with no effect for the two other variants, indicates that the effects of the risk alleles clustered at 8q24 are cancer site specific.
authors: Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom.
authors: Olivia
authors: O
authors: Fletcher
authors: Nichola
authors: N
authors: Johnson
authors: Lorna
authors: L
authors: Gibson
authors: Ben
authors: B
authors: Coupland
authors: Agnes
authors: A
authors: Fraser
authors: Angela
authors: A
authors: Leonard
authors: Isabel
authors: I
authors: dos Santos Silva
authors: Alan
authors: A
authors: Ashworth
authors: Richard
authors: R
authors: Houlston
authors: Julian
authors: J
authors: Peto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8; D004739:England / Q000453:epidemiology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012306:Risk; D012606:Scotland / Q000453:epidemiology
chemical_list: D005819:Genetic Markers