Evidence for a colorectal cancer susceptibility locus on chromosome 3q21–q24 from a high-density SNP genome-wide linkage scan

Kemp, Zoe; Carvajal‐Carmona, Luis G.; Spain, Sarah; Barclay, Ella; Gorman, Margaret; Martin, Lynn; Jaeger, Emma; Brooks, Neil; Bishop, D. Timothy; Thomas, Huw; Tomlinson, Ian; Papaemmanuil, Elli; Webb, Emily L.; Sellick, Gabrielle S.; Wood, Wendy; Evans, Gareth; Lucassen, Anneke; Houlston, Richard S.

doi:10.1093/hmg/ddl435

Cited by 13 publications

(19 citation statements)

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“…Each of the markers in the 9q22.33 region gave negative LOD scores. However, the chromosome 3q21-q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak at D3S1292 (LOD 0.9 p=0.02) 8.…”

Section: Resultssupporting

confidence: 79%

“…This region clearly stands out from the rest of the genome demonstrating linkage at multiple genetic markers over a 13.6 cM region when either study allele frequencies or CEPH allele frequencies are used in the analysis. A region on chromosome 7 with linkage (NPL LOD 1.85, p=0.032) is also reported by Kemp et al when analysis was restricted to 38 families with colorectal cancer as the diagnosis 8. The reported peak spans approximately 80 to 110 Mbp, whereas our peak spans 107 to 129 Mbp on chromosome 7.…”

Section: Discussionsupporting

confidence: 83%

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Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis

et al. 2008

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Present investigations suggest that f30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores z2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (F 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer. [Cancer Res 2008;68(21):8993-7]

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Section: Resultssupporting

confidence: 79%

Section: Discussionsupporting

confidence: 83%

Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis

et al. 2008

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“…Further, by supplementing a set of tag SNPs with additional, more uniformly spaced SNPs, we were able to capture a much larger proportion of the variability in this region. We point toward the studies by the CORGI consortium as support for these differences explaining the various results; they did not find the signal at 9q in 69 families with a mixture of colon cancer, adenomas and polyps (15), but they did replicate our findings in 57 families with >=3 affected persons, using strict age-of-onset criteria for the three phenotypes mentioned above (<75, <45, <35, respectively) (18). All of this suggests that the disease locus housed on 9q is specific to a familial syndrome with a phenotype of younger age of onset and/or severity of colon neoplasia.…”

Section: Discussionmentioning

confidence: 50%

“…Specifically, case-control association studies have identified loci for colon cancer on 8q24 (9, 10, 11), 9p24, 18q21, 11q23, 10p14, 8q23.3 and 15q13.3, 19p13, 20p12, 16q22, and 14q22 (10, 12, 13, 14). Family linkage studies have additionally reported linkage to 3q21-24, 7q31, 11q23 and 9q22-31 (15, 16, 17, 18, 19, 20). Not clear, however, are the penetrance and effect size of each of these identified variants, nor why they are found in some studies and not others.…”

Section: Introductionmentioning

confidence: 99%

Confirmation of Linkage to and Localization of Familial Colon Cancer Risk Haplotype on Chromosome 9q22

et al. 2010

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Colorectal cancer is the second leading cause of cancer mortality in adult Americans and is caused by both genetic and environmental risk factors. We have replicated our originally reported linkage signal at 9q22-31 by fine mapping an independent collection of colon cancer families. Then, using a custom array of single nucleotide polymorphisms (SNPs) densely spaced across the candidate region, we performed both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. We isolated the association effect to a five SNP haplotype centered around 98.15 megabases (Mb) on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to the GALNT12, which has been recently shown to be altered in colon tumors. Finally, we used a predictive modeling algorithm to demonstrate the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (OR=3.68) and the accuracy of our prediction model (~60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q.

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“…We investigated the relationship of these genes with colorectal cancer and summarized the annotations of these genes in Table 2. Chromosomal location 3q21-q24 was known as colorectal cancer (CRC) susceptible area [16] and 4q33-q34 was identified as common genomic alteration in CRC and genomic regions with altered DNA copy numbers [17]. It is reported that biallelic germline mutations in MYH are associated with colorectal neoplasm [18], MYH111, an isoform of MYH, could be suggested as also related with colorectal cancer.…”

Section: Resultsmentioning

confidence: 99%

Novel and simple transformation algorithm for combining microarray data sets

Kim

Jeong

et al. 2007

BMC Bioinformatics

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Background: With microarray technology, variability in experimental environments such as RNA sources, microarray production, or the use of different platforms, can cause bias. Such systematic differences present a substantial obstacle to the analysis of microarray data, resulting in inconsistent and unreliable information. Therefore, one of the most pressing challenges in the field of microarray technology is how to integrate results from different microarray experiments or combine data sets prior to the specific analysis.

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Evidence for a colorectal cancer susceptibility locus on chromosome 3q21–q24 from a high-density SNP genome-wide linkage scan

Cited by 13 publications

References 0 publications

Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis

Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis

Confirmation of Linkage to and Localization of Familial Colon Cancer Risk Haplotype on Chromosome 9q22

Novel and simple transformation algorithm for combining microarray data sets

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