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Association of Genetic Variants at 8q24 with Breast Cancer Risk

¹ Breakthrough Breast Cancer Research Centre, Institute of Cancer Research; ² Non-communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom, ³ Section of Cancer Genetics; and ⁴ Cancer Research UK Epidemiology and Genetics Unit, Institute of Cancer Research, Sutton, Surrey, United Kingdom

Requests for reprints: Julian Peto, Non-communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. Phone: 207-927-2455; Fax: 207-580-6897. E-mail: julian.peto{at}lshtm.ac.uk

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. (Cancer Epidemiol Biomarkers Prev 2008;17(3):702–5)