Multiple loci with different cancer specificities within the 8q24 gene desert.

Cancer Research UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, CB1 8RN, Cambridge, UK.
CancerSpectrum Knowledge Environment (Impact Factor: 15.16). 08/2008; 100(13):962-6. DOI: 10.1093/jnci/djn190
Source: PubMed

ABSTRACT Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.

  • [Show abstract] [Hide abstract]
    ABSTRACT: A recent study synthesized several published genome-wide association studies (GWAS) on three types of cancers and identified variants at 6p21.1 and 7p15.3 as candidate susceptibility loci for multiple types of human cancers. However, the role of these loci in the development of head and neck cancer (HNC) is still unclear. To evaluate the relationships between genetic variants in these regions and HNC risk, we genotyped two common SNPs rs2494938 at 6p21.1 and rs2285947 at 7p15.3 in a case-control study with a total of 503 HNC cases and 900 controls in Han Chinese. We found that rs2494938 at 6p21.1 was associated with a significantly increased risk of HNC in our population [AA vs. GG: adjusted odds ratio (OR)=1.84, 95% confidence interval (CI)=1.13-3.00, P=0.014; AAvs. adjusted OR=1.78, 95% CI=1.10-2.87, P=0.018]. However, no significant association was observed between rs2285947 at 7p15.3 and HNC risk. Our results suggest that genetic variants at 6p21.1 may play an important role in HNC development in Han Chinese, and rs2494938 may be a candidate marker for HNC susceptibility.
    Cancer biomarkers: section A of Disease markers 01/2015; 15(1):27-32. DOI:10.3233/CBM-140442 · 1.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of single nucleotide polymorphisms (SNPs) in the human genome have been associated with increased risk of prostate cancer. Recently, a single SNP in the region of chromosome 8q24 (rs188140481) has been associated with a three-fold increased risk of prostate cancer in Europe and North America. To establish whether rs188140481 is associated with the risk of prostate cancer in Poland, we genotyped 3467 men with prostate cancer and 1958 controls. The A allele of rs188140481 was detected in 44 of 3467 (1.3%) men with prostate cancer and in seven of 1958 (0.4%) controls (odds ratio=3.6; 95% confidence interval 1.6-7.9; P=0.0006). The allele was present in eight of 390 (2.1%) men with familial prostate cancer (odds ratio=5.8; 95% confidence interval 2.1-16.2; P=0.001). A positive family history of cancers at sites other than the prostate was observed in 27% of men who carried the rs188140481 risk allele and in 44% of noncarriers (P=0.04). No cancer at a site other than the prostate was more common in first-degree or second-degree relatives of carriers of the rs188140481 risk allele than relatives of noncarriers. The rs188140481 polymorphism in the 8q24 region confers a moderate increase in the risk of prostate cancer in Polish men. The SNP does not appear to be associated with susceptibility to cancers of other types.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 09/2014; DOI:10.1097/CEJ.0000000000000079 · 2.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by a PML-RARA fusion due to a translocation t(15;17). Its sensitivity to treatment with all-trans retinoic acid (ATRA), which causes differentiation of the abnormal promyelocytes, combined with anthracycline based chemotherapy makes it the best curable subtype of acute myeloid leukemia. A rapid and accurate diagnosis is needed in the first place to prevent (more) bleeding problems. Here we present a patient with a leukemia with an APL-like morphology but no detectable PML-RARA fusion, as demonstrated by RT-PCR and cytogenetic analysis. Results Unexpectedly, karyotyping revealed numerous double minutes (dmins). Fluorescence in situ hybridization (FISH) with DNA probes specific for the MYC-region showed the presence of multiple MYC amplicons. SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region. Conclusions The diagnosis was revised to AML, not otherwise specified (AML, NOS) and therefore therapy with ATRA was discontinued.
    Molecular Cytogenetics 12/2014; 7(1):67. DOI:10.1186/s13039-014-0067-6 · 2.66 Impact Factor

Full-text (2 Sources)

Available from
Jun 5, 2014