Association between total number of deaths, diabetes mellitus, incident cancers, and haplotypes in chromosomal region 8q24 in a prospective study.
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AbstractThe 8q24 region is a gene desert, although chromosomal aberrations and somatic amplification involving this region, including translocations involving the protooncogene c-MYC, have been frequently reported in people with cancer. To investigate the role of variants in 8q24 region, the authors analyzed data from a prospective study (n = 10,372 participants who were followed for 11 years) in which a large number of health events (>1,500) occurred (1993-1998). They genotyped all subjects for 5 candidate single nucleotide polymorphisms (rs672888, rs1447295, rs9642880, rs16901979, and rs6983267) that were identified in previous genome-wide scans. Although significant associations with individual single nucleotide polymorphisms were small in magnitude, the authors observed higher increases in the risks of different types of cancer with specific haplotypes, particularly when subjects were homozygous for the haplotype: for breast cancer and homozygotes for haplotype CAGCT, hazard ratio = 3.40, 95% confidence interval: 1.24, 9.21; for prostate cancer and grouped rare haplotypes, hazard ratio = 7.43, 95% confidence interval: 3.00, 18.37; and for brain cancer and homozygotes for haplotype CGGCT, hazard ratio = 13.48, 95% confidence interval: 3.00, 59.53. Significant associations were also observed between haplotypes and deaths from cardiovascular diseases and cerebrovascular diseases; the most stable association was between homozygotes for haplotypes CGTCG and CAGCT and total deaths in men (hazard ratio = 3.5, 95% confidence interval: 1.8, 6.9, and hazard ratio = 2.8, 95% confidence interval: 1.3, 6.4, respectively). In conclusion, the authors have observed a strong pleiotropic effect of the 8q24 region in a large prospective study. This observation can shed light on the mechanisms underlying reported associations between 8q24 variants and disparate chronic diseases.
CitationAm. J. Epidemiol. 2012, 175 (6):479-487
JournalAmerican Journal of Epidemiology
SponsorsThis work was supported by grants from the Associazione Italiana per le Ricerche sul Cancro, Italy (to GiuseppeMatullo) and the Environmental Cancer Risk Nutrition and Individual Susceptibility project (to Giuseppe Matullo and Paolo Vineis), a network of excellence operating within the European Union Sixth Framework Program, Priority 5: ‘‘Food Quality and Safety’’ (contract No.513943). This work was also supported by grants from the Compagnia di San Paolo, Turin, Italy (to Paolo Vineis and Giuseppe Matullo) and the Progetto Integrato Oncologia of the Italian government (to Paolo Vineis and Giuseppe Matullo).