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Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

Authors: Simone Picelli, Jana Vandrovcova, Siân Jones, Tatjana Djureinovic, Johanna Skoglund, Xiao-Lei Zhou, Victor E Velculescu, Bert Vogelstein, Annika Lindblom

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Familial Adenomatous Polyposis (FAP). In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer.

Methods

Statistical analysis was performed using multipoint parametric and nonparametric linkage.

Results

Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD) = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL) = 2.1).

Conclusion

The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.
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Literature
1.
go back to reference Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K: Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000, 343 (2): 78-85. 10.1056/NEJM200007133430201.CrossRefPubMed Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K: Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000, 343 (2): 78-85. 10.1056/NEJM200007133430201.CrossRefPubMed
2.
go back to reference Johns LE, Houlston RS: A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol. 2001, 96 (10): 2992-3003. 10.1111/j.1572-0241.2001.04677.x.CrossRefPubMed Johns LE, Houlston RS: A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol. 2001, 96 (10): 2992-3003. 10.1111/j.1572-0241.2001.04677.x.CrossRefPubMed
3.
go back to reference Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med. 2003, 348 (10): 919-932. 10.1056/NEJMra012242.CrossRefPubMed Lynch HT, de la Chapelle A: Hereditary colorectal cancer. N Engl J Med. 2003, 348 (10): 919-932. 10.1056/NEJMra012242.CrossRefPubMed
4.
go back to reference Olsson L, Lindblom A: Family history of colorectal cancer in a Sweden county. Fam Cancer. 2003, 2 (2): 87-93. 10.1023/A:1025734200635.CrossRefPubMed Olsson L, Lindblom A: Family history of colorectal cancer in a Sweden county. Fam Cancer. 2003, 2 (2): 87-93. 10.1023/A:1025734200635.CrossRefPubMed
5.
go back to reference Bulow S, Faurschou Nielsen T, Bulow C, Bisgaard ML, Karlsen L, Moesgaard F: The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996, 11 (2): 88-91. 10.1007/BF00342466.CrossRefPubMed Bulow S, Faurschou Nielsen T, Bulow C, Bisgaard ML, Karlsen L, Moesgaard F: The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996, 11 (2): 88-91. 10.1007/BF00342466.CrossRefPubMed
6.
go back to reference Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, Chadwick RB, Kaariainen H, Eskelinen M, Jarvinen H, Mecklin JP, de la Chapelle A: Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998, 338 (21): 1481-1487. 10.1056/NEJM199805213382101.CrossRefPubMed Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, Chadwick RB, Kaariainen H, Eskelinen M, Jarvinen H, Mecklin JP, de la Chapelle A: Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998, 338 (21): 1481-1487. 10.1056/NEJM199805213382101.CrossRefPubMed
7.
go back to reference Aaltonen L, Johns L, Järvinen H, Mecklin JP, Houlston R: Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res. 2007, 13 (1): 356-361. 10.1158/1078-0432.CCR-06-1256.CrossRefPubMed Aaltonen L, Johns L, Järvinen H, Mecklin JP, Houlston R: Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res. 2007, 13 (1): 356-361. 10.1158/1078-0432.CCR-06-1256.CrossRefPubMed
8.
go back to reference Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, Gallinger S, Bapat B, Aronson M, Hopper J, Jass J, LeMarchand L, Grove J, Potter J, Newcomb P, Terdiman JP, Conrad P, Moslein G, Goldberg R, Ziogas A, Anton-Culver H, de Andrade M, Siegmund K, Thibodeau SN, Boardman LA, Seminara D: Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005, 293 (16): 1979-1985. 10.1001/jama.293.16.1979.CrossRefPubMedPubMedCentral Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, Gallinger S, Bapat B, Aronson M, Hopper J, Jass J, LeMarchand L, Grove J, Potter J, Newcomb P, Terdiman JP, Conrad P, Moslein G, Goldberg R, Ziogas A, Anton-Culver H, de Andrade M, Siegmund K, Thibodeau SN, Boardman LA, Seminara D: Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005, 293 (16): 1979-1985. 10.1001/jama.293.16.1979.CrossRefPubMedPubMedCentral
9.
go back to reference Syngal S, Stoffel E, Chung D, Willett C, Schoetz D, Schroy P, Jagadeesh D, Morel K, Ross M: Detection of stool DNA mutations before and after treatment of colorectal neoplasia. Cancer. 2006, 106 (2): 277-283. 10.1002/cncr.21558.CrossRefPubMed Syngal S, Stoffel E, Chung D, Willett C, Schoetz D, Schroy P, Jagadeesh D, Morel K, Ross M: Detection of stool DNA mutations before and after treatment of colorectal neoplasia. Cancer. 2006, 106 (2): 277-283. 10.1002/cncr.21558.CrossRefPubMed
10.
go back to reference Houlston RS, Peto J: The search for low-penetrance cancer susceptibility alleles. Oncogene. 2004, 23 (38): 6471-6476. 10.1038/sj.onc.1207951.CrossRefPubMed Houlston RS, Peto J: The search for low-penetrance cancer susceptibility alleles. Oncogene. 2004, 23 (38): 6471-6476. 10.1038/sj.onc.1207951.CrossRefPubMed
11.
go back to reference Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E, Ferretti V, Laflamme P, Sundararajan S, Roumy S, Olivier JF, Robidoux F, Sladek R, Montpetit A, Campbell P, Bezieau S, O'shea AM, Zogopoulos G, Cotterchio M, Newcomb P, McLaughlin J, Younghusband B, Green R, Green J, Porteous ME, Campbell H, Blanche H, Sahbatou M, Tubacher E, Bonaiti-Pellie C, Buecher B, Riboli E, Kury S, Chanock SJ, Potter J, Thomas G, Gallinger S, Hudson TJ, Dunlop MG: Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24 . Nat Genet. 2007, 39 (8): 989-994. 10.1038/ng2089.CrossRefPubMed Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E, Ferretti V, Laflamme P, Sundararajan S, Roumy S, Olivier JF, Robidoux F, Sladek R, Montpetit A, Campbell P, Bezieau S, O'shea AM, Zogopoulos G, Cotterchio M, Newcomb P, McLaughlin J, Younghusband B, Green R, Green J, Porteous ME, Campbell H, Blanche H, Sahbatou M, Tubacher E, Bonaiti-Pellie C, Buecher B, Riboli E, Kury S, Chanock SJ, Potter J, Thomas G, Gallinger S, Hudson TJ, Dunlop MG: Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24 . Nat Genet. 2007, 39 (8): 989-994. 10.1038/ng2089.CrossRefPubMed
12.
go back to reference Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K, Consortium CORGI, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier JB, R. H: A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007, 39 (8): 984-989. 10.1038/ng2085.CrossRefPubMed Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K, Consortium CORGI, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier JB, R. H: A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007, 39 (8): 984-989. 10.1038/ng2085.CrossRefPubMed
13.
go back to reference Kemp Z, Thirlwell C, Sieber O, Silver A, Tomlinson I: An update on the genetics of colorectal cancer. Hum Mol Genet. 2004, 13 Spec No 2: R177-85. 10.1093/hmg/ddh247.CrossRefPubMed Kemp Z, Thirlwell C, Sieber O, Silver A, Tomlinson I: An update on the genetics of colorectal cancer. Hum Mol Genet. 2004, 13 Spec No 2: R177-85. 10.1093/hmg/ddh247.CrossRefPubMed
14.
go back to reference Cannon-Albright LA, Skolnick MH, Bishop DT, Lee RG, Burt RW: Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988, 319 (9): 533-537.CrossRefPubMed Cannon-Albright LA, Skolnick MH, Bishop DT, Lee RG, Burt RW: Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988, 319 (9): 533-537.CrossRefPubMed
15.
go back to reference Houlston RS, Collins A, Slack J, Morton NE: Dominant genes for colorectal cancer are not rare. Ann Hum Genet. 1992, 56 ( Pt 2): 99-103. 10.1111/j.1469-1809.1992.tb01136.x.CrossRef Houlston RS, Collins A, Slack J, Morton NE: Dominant genes for colorectal cancer are not rare. Ann Hum Genet. 1992, 56 ( Pt 2): 99-103. 10.1111/j.1469-1809.1992.tb01136.x.CrossRef
16.
go back to reference Skoglund J, Djureinovic T, Zhou XL, Vandrovcova J, Renkonen E, Iselius L, Bisgaard ML, Peltomaki P, Lindblom A: Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32-31.1. J Med Genet. 2006, 43 (2): e7-10.1136/jmg.2005.033928.CrossRefPubMedPubMedCentral Skoglund J, Djureinovic T, Zhou XL, Vandrovcova J, Renkonen E, Iselius L, Bisgaard ML, Peltomaki P, Lindblom A: Linkage analysis in a large Swedish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 9q22.32-31.1. J Med Genet. 2006, 43 (2): e7-10.1136/jmg.2005.033928.CrossRefPubMedPubMedCentral
17.
go back to reference Wiesner GL, Daley D, Lewis S, Ticknor C, Platzer P, Lutterbaugh J, MacMillen M, Baliner B, Willis J, Elston RC, Markowitz SD: A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2. Proc Natl Acad Sci U S A. 2003, 100 (22): 12961-12965. 10.1073/pnas.2132286100.CrossRefPubMedPubMedCentral Wiesner GL, Daley D, Lewis S, Ticknor C, Platzer P, Lutterbaugh J, MacMillen M, Baliner B, Willis J, Elston RC, Markowitz SD: A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2. Proc Natl Acad Sci U S A. 2003, 100 (22): 12961-12965. 10.1073/pnas.2132286100.CrossRefPubMedPubMedCentral
18.
go back to reference Kemp Z, Carvajal-Carmona LG, Barclay E, Gorman M, Martin L, Wood W, Rowan A, Donohue C, Spain S, Jaeger E, Evans DG, Maher ER, Bishop T, Thomas H, Houlston R, Tomlinson I, Colorectal Tumour Gene Identification Study Consortium: Evidence of linkage to chromosome 9q22.33 in colorectal cancer kindreds from the United Kingdom. Cancer Res. 2006, 66 (10): 5003-5006. 10.1158/0008-5472.CAN-05-4074.CrossRefPubMed Kemp Z, Carvajal-Carmona LG, Barclay E, Gorman M, Martin L, Wood W, Rowan A, Donohue C, Spain S, Jaeger E, Evans DG, Maher ER, Bishop T, Thomas H, Houlston R, Tomlinson I, Colorectal Tumour Gene Identification Study Consortium: Evidence of linkage to chromosome 9q22.33 in colorectal cancer kindreds from the United Kingdom. Cancer Res. 2006, 66 (10): 5003-5006. 10.1158/0008-5472.CAN-05-4074.CrossRefPubMed
19.
go back to reference Djureinovic T, Skoglund J, Vandrovcova J, Zhou X, Kalushkova A, Iselius L, Lindblom A: A genome-wide linkage analysis in Swedish families with hereditary non-FAP/non-HNPCC colorectal cancer. Gut. 2005, 55 (3): 362-368. 10.1136/gut.2005.075333.CrossRefPubMed Djureinovic T, Skoglund J, Vandrovcova J, Zhou X, Kalushkova A, Iselius L, Lindblom A: A genome-wide linkage analysis in Swedish families with hereditary non-FAP/non-HNPCC colorectal cancer. Gut. 2005, 55 (3): 362-368. 10.1136/gut.2005.075333.CrossRefPubMed
20.
go back to reference Zhou XL, Eriksson U, Werelius B, Kressner U, Sun XF, Lindblom A: Definition of candidate low risk APC alleles in a Swedish population. Int J Cancer. 2004, 110 (4): 550-557. 10.1002/ijc.20173.CrossRefPubMed Zhou XL, Eriksson U, Werelius B, Kressner U, Sun XF, Lindblom A: Definition of candidate low risk APC alleles in a Swedish population. Int J Cancer. 2004, 110 (4): 550-557. 10.1002/ijc.20173.CrossRefPubMed
21.
go back to reference Zhou XL, Djureinovic T, Werelius B, Lindmark G, Sun XF, Lindblom A, Group SLRCC: Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer. Genet Test. 2005, 9 (2): 147-151. 10.1089/gte.2005.9.147.CrossRefPubMed Zhou XL, Djureinovic T, Werelius B, Lindmark G, Sun XF, Lindblom A, Group SLRCC: Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer. Genet Test. 2005, 9 (2): 147-151. 10.1089/gte.2005.9.147.CrossRefPubMed
22.
go back to reference Lagerstedt Robinson K, Liu T, Vandrovcova J, Halvarsson B, Clendenning M, Frebourg T, Papadopoulos N, Kinzler KW, Vogelstein B, Peltomäki P, Kolodner RD, Nilbert M, Lindblom A: Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007, 99 (4): 291-299. 10.1093/jnci/djk051.CrossRefPubMed Lagerstedt Robinson K, Liu T, Vandrovcova J, Halvarsson B, Clendenning M, Frebourg T, Papadopoulos N, Kinzler KW, Vogelstein B, Peltomäki P, Kolodner RD, Nilbert M, Lindblom A: Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007, 99 (4): 291-299. 10.1093/jnci/djk051.CrossRefPubMed
24.
go back to reference O'Connell JR, Weeks DE: PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998, 63 (1): 259-266. 10.1086/301904.CrossRefPubMedPubMedCentral O'Connell JR, Weeks DE: PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998, 63 (1): 259-266. 10.1086/301904.CrossRefPubMedPubMedCentral
25.
go back to reference Sobel E, Lange K: Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet. 1996, 58 (6): 1323-1337.PubMedPubMedCentral Sobel E, Lange K: Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet. 1996, 58 (6): 1323-1337.PubMedPubMedCentral
26.
go back to reference Cottingham RW, Idury RM, Schaffer AA: Faster sequential genetic linkage computations. Am J Hum Genet. 1993, 53 (1): 252-263.PubMedPubMedCentral Cottingham RW, Idury RM, Schaffer AA: Faster sequential genetic linkage computations. Am J Hum Genet. 1993, 53 (1): 252-263.PubMedPubMedCentral
27.
go back to reference Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006, 314 (5797): 268-274. 10.1126/science.1133427.CrossRefPubMed Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006, 314 (5797): 268-274. 10.1126/science.1133427.CrossRefPubMed
28.
go back to reference Liu HX, Zhou XL, Liu T, Werelius B, Lindmark G, Dahl N, Lindblom A: The role of hMLH3 in familial colorectal cancer. Cancer Res. 2003, 63 (8): 1894-1899.PubMed Liu HX, Zhou XL, Liu T, Werelius B, Lindmark G, Dahl N, Lindblom A: The role of hMLH3 in familial colorectal cancer. Cancer Res. 2003, 63 (8): 1894-1899.PubMed
31.
go back to reference Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21 (2): 263-265. 10.1093/bioinformatics/bth457.CrossRefPubMed Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21 (2): 263-265. 10.1093/bioinformatics/bth457.CrossRefPubMed
32.
go back to reference Kemp Z, Carvajal-Carmona L, Spain S, Barclay E, Gorman M, Martin L, Jaeger E, Brooks N, Bishop DT, Thomas H, Tomlinson I, Papaemmanuil E, Webb E, Sellick GS, W W, Evans G, Lucassen A, Maher ER, Houlston RS, ColoRectal tumour Gene Identification (CoRGI) Study Consortium: Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan. Hum Mol Genet. 2006, 19 (15): 2903-2910. 10.1093/hmg/ddl231.CrossRef Kemp Z, Carvajal-Carmona L, Spain S, Barclay E, Gorman M, Martin L, Jaeger E, Brooks N, Bishop DT, Thomas H, Tomlinson I, Papaemmanuil E, Webb E, Sellick GS, W W, Evans G, Lucassen A, Maher ER, Houlston RS, ColoRectal tumour Gene Identification (CoRGI) Study Consortium: Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan. Hum Mol Genet. 2006, 19 (15): 2903-2910. 10.1093/hmg/ddl231.CrossRef
Metadata
Title
Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q
Authors
Simone Picelli
Jana Vandrovcova
Siân Jones
Tatjana Djureinovic
Johanna Skoglund
Xiao-Lei Zhou
Victor E Velculescu
Bert Vogelstein
Annika Lindblom
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-87

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