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BMC Cancer
Published in: BMC Cancer 1/2007

Open Access 01-12-2007 | Research article

CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer

Authors: Sara Margolin, Hans Eiberg, Annika Lindblom, Marie Luise Bisgaard

Published in: BMC Cancer | Issue 1/2007

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Abstract

Background

A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations.

Methods

We analyzed the prevalence of CHEK2 1100delC in 763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452) and from a familial cancer clinic (n = 311), the detailed family history was known in both groups.

Results

The variant was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03). There was no increased prevalence in sporadic patients (0.3%). The variant was most frequent in young familial patients (5.1% of cases ≤45 years, p = 0.003). The mean age at diagnosis of variant carriers was 12 years lower than in non-carriers (p = 0.001).

Conclusion

In conclusion, CHEK2 1100delC exists in the Swedish population. The prevalence is increased in familial breast cancer and the variant seems to influence age at onset.
Appendix
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Literature
1.
2.
Antoniou AC, Pharoah PD, McMullan G, Day NE, Stratton MR, Peto J, Ponder BJ, Easton DF: A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes. Br J Cancer. 2002, 86: 76-83. 10.1038/sj.bjc.6600008.CrossRefPubMedPubMedCentral
3.
Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA: Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002, 31: 33-36. 10.1038/ng853.CrossRefPubMed
4.
Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF: A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1999, 8: 843-854.PubMed
5.
Antoniou AC, Easton DF: Polygenic inheritance of breast cancer: Implications for design of association studies. Genet Epidemiol. 2003, 25: 190-202. 10.1002/gepi.10261.CrossRefPubMed
6.
Bartek J, Lukas J: Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell. 2003, 3: 421-429. 10.1016/S1535-6108(03)00110-7.CrossRefPubMed
7.
Vahteristo P, Bartkova J, Eerola H, Syrjakoski K, Ojala S, Kilpivaara O, Tamminen A, Kononen J, Aittomaki K, Heikkila P, Holli K, Blomqvist C, Bartek J, Kallioniemi OP, Nevanlinna H: A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet. 2002, 71: 432-438. 10.1086/341943.CrossRefPubMedPubMedCentral
8.
Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, van Veghel-Plandsoen M, Elstrodt F, van Duijn C, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton D, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Evans DG, Houlston R, Murday V, Narod S, Peretz T, Peto J, Phelan C, Zhang HX, Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson KL, Weber B, Rahman N, Stratton MR: Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002, 31: 55-59. 10.1038/ng879.CrossRefPubMed
9.
Oldenburg RA, Kroeze-Jansema K, Kraan J, Morreau H, Klijn JG, Hoogerbrugge N, Ligtenberg MJ, van Asperen CJ, Vasen HF, Meijers C, Meijers-Heijboer H, de Bock TH, Cornelisse CJ, Devilee P: The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families. Cancer Res. 2003, 63: 8153-8157.PubMed
10.
CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004, 74: 1175-1182. 10.1086/421251.
11.
Lindblom A: A molecular study on familial breast cancer. Departments of Clinical Genetics and Oncology, Karolinska Hospital. 1993, Stockholm, Karolinska Institute
12.
Zelada-Hedman M, Wasteson Arver B, Claro A, Chen J, Werelius B, Kok H, Sandelin K, Hakansson S, Andersen TI, Borg A, Borresen Dale AL, Lindblom A: A screening for BRCA1 mutations in breast and breast-ovarian cancer families from the Stockholm region. Cancer Res. 1997, 57: 2474-2477.PubMed
13.
Chen J, Hedman MZ, Arver BW, Sigurdsson S, Eyfjord JE, Lindblom A: BRCA2 germline mutations in Swedish breast cancer families. Eur J Hum Genet. 1998, 6: 134-139. 10.1038/sj.ejhg.5200167.CrossRefPubMed
14.
Margolin S, Werelius B, Fornander T, Lindblom A: BRCA1 mutations in a population-based study of breast cancer in Stockholm County. Genet Test. 2004, 8: 127-132.CrossRefPubMed
15.
Mateus Pereira LH, Sigurdson AJ, Doody MM, Pineda MA, Alexander BH, Greene MH, Struewing JP: CHEK2:1100delC and female breast cancer in the United States. Int J Cancer. 2004, 112: 541-543. 10.1002/ijc.20439.CrossRefPubMed
16.
Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, Hollestelle A, Elstrodt F, van den Bos R, de Snoo A, Fat GT, Brekelmans C, Jagmohan S, Franken P, Verkuijlen P, van den Ouweland A, Chapman P, Tops C, Moslein G, Burn J, Lynch H, Klijn J, Fodde R, Schutte M: The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet. 2003, 72: 1308-1314. 10.1086/375121.CrossRefPubMedPubMedCentral
17.
Offit K, Pierce H, Kirchhoff T, Kolachana P, Rapaport B, Gregersen P, Johnson S, Yossepowitch O, Huang H, Satagopan J, Robson M, Scheuer L, Nafa K, Ellis N: Frequency of CHEK2*1100delC in New York breast cancer cases and controls. BMC Med Genet. 2003, 4: 1-10.1186/1471-2350-4-1.CrossRefPubMedPubMedCentral
18.
Jekimovs CR, Chen X, Arnold J, Gatei M, Richard DJ, Spurdle AB, Khanna KK, Chenevix-Trench G: Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals. Br J Cancer. 2005, 92: 784-790. 10.1038/sj.bjc.6602381.CrossRefPubMedPubMedCentral
19.
Kleibl Z, Novotny J, Bezdickova D, Malik R, Kleiblova P, Foretova L, Petruzelka L, Ilencikova D, Cinek P, Pohlreich P: The CHEK2 c.1100delC germline mutation rarely contributes to breast cancer development in the Czech Republic. Breast Cancer Res Treat. 2005, 90: 165-167. 10.1007/s10549-004-4023-8.CrossRefPubMed
20.
Osorio A, Rodriguez-Lopez R, Diez O, de la Hoya M, Ignacio Martinez J, Vega A, Esteban-Cardenosa E, Alonso C, Caldes T, Benitez J: The breast cancer low-penetrance allele 1100delC in the CHEK2 gene is not present in Spanish familial breast cancer population. Int J Cancer. 2004, 108: 54-56. 10.1002/ijc.11414.CrossRefPubMed
21.
Wagenius M, Borg A, Johansson L, Giwercman A, Bratt O: CHEK2*1100delC is not an important high-risk gene in families with hereditary prostate cancer in southern Sweden. Scand J Urol Nephrol. 2006, 40: 23-25. 10.1080/00365590500368518.CrossRefPubMed
22.
Isinger A, Bhat M, Borg A, Nilbert M: CHEK2 1100delC in patients with metachronous cancers of the breast and the colorectum. BMC Cancer. 2006, 6: 64-10.1186/1471-2407-6-64.CrossRefPubMedPubMedCentral
23.
Einarsdottir K, Humphreys K, Bonnard C, Palmgren J, Iles MM, Sjolander A, Li Y, Chia KS, Liu ET, Hall P, Liu J, Wedren S: Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk. PLoS Med. 2006, 3: e168-10.1371/journal.pmed.0030168.CrossRefPubMedPubMedCentral
24.
de Bock GH, Schutte M, Krol-Warmerdam EM, Seynaeve C, Blom J, Brekelmans CT, Meijers-Heijboer H, van Asperen CJ, Cornelisse CJ, Devilee P, Tollenaar RA, Klijn JG: Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant. J Med Genet. 2004, 41: 731-735. 10.1136/jmg.2004.019737.CrossRefPubMedPubMedCentral
25.
Rashid MU, Jakubowska A, Justenhoven C, Harth V, Pesch B, Baisch C, Pierl CB, Bruning T, Ko Y, Benner A, Wichmann HE, Brauch H, Hamann U: German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer. Eur J Cancer. 2005, 41: 2896-2903. 10.1016/j.ejca.2005.04.049.CrossRefPubMed
26.
Weischer M, Bojesen SE, Tybjaerg-Hansen A, Axelsson CK, Nordestgaard BG: Increased risk of breast cancer associated with CHEK2*1100delC. J Clin Oncol. 2007, 25: 57-63. 10.1200/JCO.2005.05.5160.CrossRefPubMed
27.
de Jong MM, Nolte IM, Te Meerman GJ, van der Graaf WT, Oosterom E, Bruinenberg M, Steege G, Oosterwijk JC, van der Hout AH, Boezen HM, Schaapveld M, Kleibeuker JH, de Vries EG: No increased susceptibility to breast cancer from combined CHEK2 1100delC genotype and the HLA class III region risk factors. Eur J Cancer. 2005, 41: 1819-1823. 10.1016/j.ejca.2005.04.035.CrossRefPubMed
28.
Kilpivaara O, Bartkova J, Eerola H, Syrjakoski K, Vahteristo P, Lukas J, Blomqvist C, Holli K, Heikkila P, Sauter G, Kallioniemi OP, Bartek J, Nevanlinna H: Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. Int J Cancer. 2005, 113: 575-580. 10.1002/ijc.20638.CrossRefPubMed
29.
Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA: Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999, 286: 2528-2531. 10.1126/science.286.5449.2528.CrossRefPubMed
30.
Dufault MR, Betz B, Wappenschmidt B, Hofmann W, Bandick K, Golla A, Pietschmann A, Nestle-Kramling C, Rhiem K, Huttner C, von Lindern C, Dall P, Kiechle M, Untch M, Jonat W, Meindl A, Scherneck S, Niederacher D, Schmutzler RK, Arnold N: Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer. 2004, 110: 320-325. 10.1002/ijc.20073.CrossRefPubMed
31.
Sodha N, Houlston RS, Bullock S, Yuille MA, Chu C, Turner G, Eeles RA: Increasing evidence that germline mutations in CHEK2 do not cause Li-Fraumeni syndrome. Hum Mutat. 2002, 20: 460-462. 10.1002/humu.10136.CrossRefPubMed
Metadata
Title
CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer
Authors
Sara Margolin
Hans Eiberg
Annika Lindblom
Marie Luise Bisgaard
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-7-163

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