Skip to main content

Advertisement

SpringerLink
Log in

SISE matters: the Sum of Information on Seventy-yr-old Equivalents measures pedigree information content when assessing the risk of HNPCC in a family

  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Hereditary non-polyposis colon cancer (HNPCC) is a significant cause of colorectal and other malignancies. Due to the lack of features that reliably differentiate between a sporadic case and an inherited case of colon cancer, it is likely that HNPCC is under reported. The diagnosis of HNPCC relies heavily on finding multiple cases of colorectal or other specific cancers within a family. In the absence of a significant family history, a diagnosis of HNPCC is seldom considered. We postulate that small kinships – or, more specifically, kinships with a low information content – are more likely to be designated as having a low risk of an inherited cancer predisposition than are large kinships. This has the potential to exacerbate the under-diagnosis of HNPCC in small families, leading to inadequate treatment, follow-up and family counselling. We have developed an objective measure of the information content of individual pedigrees called the Sum of Information on Seventy-yr-old Equivalents (SISE) coefficient. The SISE coefficient is a function of the number of relatives in a kinship and their relationship to the proband, of their ages and of the age-dependent penetrance of HNPCC mutations. A population-based series of colorectal cancer cases was assessed, by currently accepted methods, for the likelihood of there being an HNPCC mutation segregating in each family. We observed that families with a low SISE coefficient were significantly more likely to be designated at low risk of HNPCC (P≤0.001). Using a cumulative binomial distribution function, we estimated the likelihood of observing multiple cancers in families of different SISE coefficients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. L Spirio S Olschwang J Groden et al. (1993) ArticleTitleAlleles of the APC gene: an attenuated form of familial polyposis Cell 75 951–7 Occurrence Handle10.1016/0092-8674(93)90538-2 Occurrence Handle1:CAS:528:DyaK2cXltFOquw%3D%3D Occurrence Handle8252630

    Article  CAS  PubMed  Google Scholar 

  2. H Lamlum N Al Tassan E Jaeger et al. (2000) ArticleTitleGermline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q Hum Mol Genet 9 2215–21 Occurrence Handle1:CAS:528:DC%2BD3cXnt1yntL4%3D Occurrence Handle11001924

    CAS  PubMed  Google Scholar 

  3. P. Peltomaki (2003) ArticleTitleRole of DNA mistake repair defects in the pathogenesis of human cancer J Clin Oncol 21 1174–9 Occurrence Handle10.1200/JCO.2003.04.060 Occurrence Handle1:CAS:528:DC%2BD2cXpsVGqt70%3D Occurrence Handle12637487

    Article  CAS  PubMed  Google Scholar 

  4. S Narayan D. Roy (2003) ArticleTitleRole of APC and DNA mistake repair genes in the development of colorectal cancers Mol Cancer 2 41–55 Occurrence Handle10.1186/1476-4598-2-41 Occurrence Handle14672538

    Article  PubMed  Google Scholar 

  5. HF Vasen JP Mecklin PM Khan HT. Lynch (1991) ArticleTitleThe International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) Dis Colon Rectum 34 424–5 Occurrence Handle1:STN:280:By6B3MrpslU%3D Occurrence Handle2022152

    CAS  PubMed  Google Scholar 

  6. HF Vasen P Watson JP Mecklin HT. Lynch (1999) ArticleTitleNew clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC Gastroenterology 116 1453–6 Occurrence Handle1:STN:280:DyaK1M3nvVamuw%3D%3D Occurrence Handle10348829

    CAS  PubMed  Google Scholar 

  7. ML Slattery TR Levin K Ma et al. (2003) ArticleTitleFamily history and colorectal cancer: predictors of risk Cancer Causes Control 14 879–87 Occurrence Handle10.1023/B:CACO.0000003840.94591.76 Occurrence Handle1:STN:280:DC%2BD3sngtVGmsQ%3D%3D Occurrence Handle14682445

    Article  CAS  PubMed  Google Scholar 

  8. HJ Murff DR Spigel S. Syngal (2004) ArticleTitleDoes this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history JAMA 292 1480–9 Occurrence Handle10.1001/jama.292.12.1480 Occurrence Handle1:CAS:528:DC%2BD2cXnvFGiu70%3D Occurrence Handle15383520

    Article  CAS  PubMed  Google Scholar 

  9. PJ Ainsworth D Koscinski BP Fraser JA. Stuart (2004) ArticleTitleFamily cancer histories predictive of a high-risk of hereditary non-polyposis colorectal cancer associate significantly with a genomic rearrangement in hMSH2 or hMLH1 Clin Genet 66 183–8 Occurrence Handle10.1111/j.0009-9163.2004.00282.x Occurrence Handle1:STN:280:DC%2BD2cvotFWiug%3D%3D Occurrence Handle15324316

    Article  CAS  PubMed  Google Scholar 

  10. DG Evans DM Eccles N Rahman et al. (2004) ArticleTitleA new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO J Med Genet 41 474–80 Occurrence Handle10.1136/jmg.2003.017996 Occurrence Handle1:CAS:528:DC%2BD2cXlsl2gsbc%3D Occurrence Handle15173236

    Article  CAS  PubMed  Google Scholar 

  11. RJ Scott M McPhillips CJ Meldrum et al. (2001) ArticleTitleHereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds Am J Hum Genet 68 118–27 Occurrence Handle10.1086/316942 Occurrence Handle1:CAS:528:DC%2BD3MXnt1ehtQ%3D%3D Occurrence Handle11112663

    Article  CAS  PubMed  Google Scholar 

  12. MA Jenkins L Baglietto GS Dite et al. (2002) ArticleTitleAfter hMSH2 and hMLH1 – what next? Analysis of three-generational, population-based, early-onset colorectal cancer families Int J Cancer 102 166–71

    Google Scholar 

  13. B Halvarsson A Lindblom E Rambech et al. (2003) ArticleTitleMicrosatellite instability analysis and/or immunostaining for the diagnosis of hereditary nonpolyposis colorectal cancer? Virchows Arch 444 135–41 Occurrence Handle14652751

    PubMed  Google Scholar 

  14. HT Lynch JF. Lynch (2000) ArticleTitleHereditary nonpolyposis colorectal cancer Semin Surg Oncol 18 305–13 Occurrence Handle10.1002/(SICI)1098-2388(200006)18:4<305::AID-SSU5>3.0.CO;2-A Occurrence Handle1:STN:280:DC%2BD3c3ms1Cktw%3D%3D Occurrence Handle10805952

    Article  CAS  PubMed  Google Scholar 

  15. Partnership and reproductive behaviour in low-fertility countries. Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat 2003ESA/P/WP.177.

  16. MG Dunlop SM Farrington AD Carothers et al. (1997) ArticleTitleCancer risk associated with germline DNA mistake repair gene mutations Hum Mol Genet 6 105–10 Occurrence Handle10.1093/hmg/6.1.105 Occurrence Handle1:CAS:528:DyaK2sXlslCmtg%3D%3D Occurrence Handle9002677

    Article  CAS  PubMed  Google Scholar 

  17. HF Vasen A Stormorken FH Menko et al. (2001) ArticleTitleMsh2 mutation carriers are at higher risk of cancer than mlh1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families J Clin Oncol 19 4074–80 Occurrence Handle1:STN:280:DC%2BD3MrlsVSgsw%3D%3D Occurrence Handle11600610

    CAS  PubMed  Google Scholar 

  18. BM Buttin MA Powell DG Mutch et al. (2004) ArticleTitlePenetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history Am J Hum Genet 74 1262–9 Occurrence Handle10.1086/421332 Occurrence Handle1:CAS:528:DC%2BD2cXks1CqsrY%3D Occurrence Handle15098177

    Article  CAS  PubMed  Google Scholar 

  19. HFA Vasen JT Wijnen FH Menko et al. (1996) ArticleTitleCancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis Gastroenterology 110 1020–7 Occurrence Handle1:STN:280:BymC1czhtlI%3D Occurrence Handle8612988

    CAS  PubMed  Google Scholar 

  20. G Moslein S Pistorius HD Saeger HK. Schackert (2003) ArticleTitlePreventive surgery for colon cancer in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer syndrome Langenbecks Arch Surg 388 9–16 Occurrence Handle12690475

    PubMed  Google Scholar 

  21. WH VostotNederveen Cappel Particlede E Buskens P Duijvendijk Particlevan et al. (2003) ArticleTitleDecision analysis in the surgical treatment of colorectal cancer due to a MMR gene defect Gut 52 1752–5 Occurrence Handle10.1136/gut.52.12.1752 Occurrence Handle14633956

    Article  PubMed  Google Scholar 

  22. S Todd SL Sherman SL. Naylor (1993) ArticleTitleDinucleotide repeat loci contribute highly informative genetic markers to the human chromosome 2 linkage map Genomics 16 612–8 Occurrence Handle10.1006/geno.1993.1238 Occurrence Handle1:CAS:528:DyaK3sXmsVaitb0%3D Occurrence Handle8100800

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine, Memorial University, St. John’s, Newfoundland, A1B 3V6, Canada

    R. C. Green & H. B. Younghusband

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

    J. R. McLaughlin

Authors
  1. R. C. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. R. McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. B. Younghusband
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. C. Green.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Green, R.C., McLaughlin, J.R. & Younghusband, H.B. SISE matters: the Sum of Information on Seventy-yr-old Equivalents measures pedigree information content when assessing the risk of HNPCC in a family. Familial Cancer 4, 169–175 (2005). https://doi.org/10.1007/s10689-004-7251-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-004-7251-5

Keywords

Search

Navigation