The 8q24 region is a gene desert but chromosomal aberrations and somatic amplification involving this region have been frequently reported in cancer, including translocations involving the proto-oncogene c-MYC. To investigate the role of variants in the 8q24 region, we have analysed a prospective study (N=10372) followed for 10 years, in which a large number of health events (N>1,500) occurred. We genotyped all subjects for 5 candidate SNPs (rs672888, rs1447295, rs9642880, rs16901979, rs6983267) identified in previous genome-wide scans. . While significant associations with single SNPs had smaller effects, we observed higher increases in risk for specific haplotypes and cancer types, in particular when subjects were homozygous for the haplotype: breast, haplotype 5/5 (CAGCT), HR=3.40 (1.24-9.21); prostate, grouped rare haplotypes, HR= 7.43 (3.00-18.37); brain, haplotype 7/7 (CGGCT), HR=13.48 (3.00-59.53). Significant associations were also observed between haplotypes and deaths from cardiovascular diseases and cerebrovascular diseases andthe most stable association was between haplotypes 4/4 and 5/5 and total deaths in men (217 observations; HR=3.5, 95% CI 1.8- 6.9; and 2.8, 1.3-6.4 respectively). In conclusion, we have observed a strong pleiotropic effect of the region in a large prospective study. This observation can shed light on the underlying mechanisms that link 8q24 variants with disparate diseases.

Association Between Total Number of Deaths, Diabetes Mellitus, Incident Cancers, and Haplotypes in Chromosomal Region 8q24 in a Prospective Study

GUARRERA, Simonetta;RICCERI, FULVIO;POLIDORO, Silvia;SACERDOTE, Carlotta;Alessandra Allione;ROSA, FABIO;CRITELLI, ROSSANA;RUSSO, ALESSIA;VINEIS, Paolo;MATULLO, Giuseppe
2012

Abstract

The 8q24 region is a gene desert but chromosomal aberrations and somatic amplification involving this region have been frequently reported in cancer, including translocations involving the proto-oncogene c-MYC. To investigate the role of variants in the 8q24 region, we have analysed a prospective study (N=10372) followed for 10 years, in which a large number of health events (N>1,500) occurred. We genotyped all subjects for 5 candidate SNPs (rs672888, rs1447295, rs9642880, rs16901979, rs6983267) identified in previous genome-wide scans. . While significant associations with single SNPs had smaller effects, we observed higher increases in risk for specific haplotypes and cancer types, in particular when subjects were homozygous for the haplotype: breast, haplotype 5/5 (CAGCT), HR=3.40 (1.24-9.21); prostate, grouped rare haplotypes, HR= 7.43 (3.00-18.37); brain, haplotype 7/7 (CGGCT), HR=13.48 (3.00-59.53). Significant associations were also observed between haplotypes and deaths from cardiovascular diseases and cerebrovascular diseases andthe most stable association was between haplotypes 4/4 and 5/5 and total deaths in men (217 observations; HR=3.5, 95% CI 1.8- 6.9; and 2.8, 1.3-6.4 respectively). In conclusion, we have observed a strong pleiotropic effect of the region in a large prospective study. This observation can shed light on the underlying mechanisms that link 8q24 variants with disparate diseases.
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http://www.ncbi.nlm.nih.gov/pubmed/22350583
Deaths; Diabetes Mellitus; Cancers; DNA polymorphisms; Haplotypes; 8q24; genetic pleiotropy; prospective study
Simonetta Guarrera; Fulvio Ricceri; Silvia Polidoro; Carlotta Sacerdote; Alessandra Allione; Fabio Rosa; Floriana Voglino; Rossana Critelli; Alessia Russo; Paolo Vineis; Giuseppe Matullo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/93975
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