Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.
Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3859667?pdf=render |
| _version_ | 1819091984450584576 |
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| author | Vinaykumar Kontham Susanna von Holst Annika Lindblom |
| author_facet | Vinaykumar Kontham Susanna von Holst Annika Lindblom |
| author_sort | Vinaykumar Kontham |
| collection | DOAJ |
| description | Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683) and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies. |
| first_indexed | 2024-12-21T22:48:24Z |
| format | Article |
| id | doaj.art-83db5b5f58284dfe84ce0397ed6390d1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T22:48:24Z |
| publishDate | 2013-01-01 |
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| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-83db5b5f58284dfe84ce0397ed6390d12022-12-21T18:47:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8393610.1371/journal.pone.0083936Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden.Vinaykumar KonthamSusanna von HolstAnnika LindblomFamily history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased risk of colorectal cancer. The families were ascertained from the department of clinical genetics at the Karolinska University Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide polymorphism array chips. Parametric- and non-parametric linkage analyses were computed using MERLIN in all and subsets of families. No statistically significant result was seen, however, there were suggestive positive HLODs above two in parametric linkage analysis. This was observed in a recessive model for high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683) and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for any of the families. Our linkage study provided additional support for the previously suggested region on chromosome 9 and suggested additional loci to be involved in colorectal cancer risk. Sequencing of genes in the regions will be done in future studies.http://europepmc.org/articles/PMC3859667?pdf=render |
| spellingShingle | Vinaykumar Kontham Susanna von Holst Annika Lindblom Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden. PLoS ONE |
| title | Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden. |
| title_full | Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden. |
| title_fullStr | Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden. |
| title_full_unstemmed | Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden. |
| title_short | Linkage analysis in familial non-Lynch syndrome colorectal cancer families from Sweden. |
| title_sort | linkage analysis in familial non lynch syndrome colorectal cancer families from sweden |
| url | http://europepmc.org/articles/PMC3859667?pdf=render |
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