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Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis.

Publication ,  Journal Article
Neklason, DW; Kerber, RA; Nilson, DB; Anton-Culver, H; Schwartz, AG; Griffin, CA; Lowery, JT; Schildkraut, JM; Evans, JP; Tomlinson, GE ...
Published in: Cancer Res
November 1, 2008

Present investigations suggest that approximately 30% 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 >or=2.0: 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 (+/- 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.

Duke Scholars

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

November 1, 2008

Volume

68

Issue

21

Start / End Page

8993 / 8997

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Middle Aged
  • Lod Score
  • Humans
  • Genome, Human
  • Genetic Predisposition to Disease
  • Colorectal Neoplasms
  • Chromosomes, Human, Pair 7
  • Aged, 80 and over
  • Aged
 

Citation

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Chicago
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MLA
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Neklason, D. W., Kerber, R. A., Nilson, D. B., Anton-Culver, H., Schwartz, A. G., Griffin, C. A., … Burt, R. W. (2008). Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis. Cancer Res, 68(21), 8993–8997. https://doi.org/10.1158/0008-5472.CAN-08-1376
Neklason, Deborah W., Richard A. Kerber, David B. Nilson, Hoda Anton-Culver, Ann G. Schwartz, Constance A. Griffin, Jan T. Lowery, et al. “Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis.Cancer Res 68, no. 21 (November 1, 2008): 8993–97. https://doi.org/10.1158/0008-5472.CAN-08-1376.
Neklason DW, Kerber RA, Nilson DB, Anton-Culver H, Schwartz AG, Griffin CA, et al. Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis. Cancer Res. 2008 Nov 1;68(21):8993–7.
Neklason, Deborah W., et al. “Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis.Cancer Res, vol. 68, no. 21, Nov. 2008, pp. 8993–97. Pubmed, doi:10.1158/0008-5472.CAN-08-1376.
Neklason DW, Kerber RA, Nilson DB, Anton-Culver H, Schwartz AG, Griffin CA, Lowery JT, Schildkraut JM, Evans JP, Tomlinson GE, Strong LC, Miller AR, Stopfer JE, Finkelstein DM, Nadkarni PM, Kasten CH, Mineau GP, Burt RW. Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis. Cancer Res. 2008 Nov 1;68(21):8993–8997.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

November 1, 2008

Volume

68

Issue

21

Start / End Page

8993 / 8997

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Middle Aged
  • Lod Score
  • Humans
  • Genome, Human
  • Genetic Predisposition to Disease
  • Colorectal Neoplasms
  • Chromosomes, Human, Pair 7
  • Aged, 80 and over
  • Aged