Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-06-23T06:07:43.005Z Has data issue: false hasContentIssue false
  • English
  • Français

A Dynamic Family History model Of Hereditary Nonpolyposis Colorectal Cancer and Critical Illness Insurance

Published online by Cambridge University Press:  10 May 2011

L. Lu ,
A. S. Macdonald ,
H. R. Waters  and
F. Yu
L. Lu
Affiliation:
Department of Actuarial Mathematics and Statistics and the Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, U.K., Email: A.S.Macdonald@ma.hw.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterised by the familial aggregation of cancer of the colon and rectum (CRC). It may be caused by any of five mutations in DNA mismatch repair (MMR) genes or by non-genetic factors, such as life style. However, it accounts for only about 2% of CRC, which is a very common cancer. Previous actuarial models, of diseases with only genetic causes, assumed that a family history of the disease shows mutations to be present, but this is not true of HNPCC. This is a significant limitation, since the best information available to an underwriter (especially if the use of genetic test results is banned) is likely to be knowledge of a family history of CRC. We present a Markov model of CRC and HNPCC, which includes the presence of a family history of CRC as a state, and estimate its intensities allowing for MMR genotype. Using this we find the MMR mutation probabilities for an insurance applicant with a family history of CRC. Our model greatly simplifies the intensive computational burden of finding such probabilities by integrating over complex models of hidden family structure. We estimate the costs of critical illness insurance given the applicant's genotype or the presence of a family history. We then consider what the cost of adverse selection might be, if insurers are unable to use genetic tests or family history information. We also consider the effect of using alternative definitions of a family history in underwriting.

Keywords

Adverse SelectionCritical Illness InsuranceFamily HistoryGenetic TestsHereditary Nonpolyposis Colorectal CancerMoratoria
Type
Papers
Information
Annals of Actuarial Science , Volume 2 , Issue 2 , September 2007 , pp. 289 - 325
Copyright
Copyright © Institute and Faculty of Actuaries 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aaltonen, L., Peltomaki, P., Leach, F., Sistonen, P., Pylkkanen, L. & Mecklin, L. (1993). Clues to the pathologenesis of familial colorectal cancer. Science, 260, 812–816.CrossRefGoogle Scholar
Aaltonen, L., Salovaara, R., Kristo, P., Canzian, F., Hemminki, A., Peltomaki, P., Chadwick, R., Kaarianen, H., Eskelinen, M., Jarvinen, H., Mecklin, J. & Chapelle, A. (1998). Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. The New England Journal of Medicine, 338, 1481–1487.CrossRefGoogle ScholarPubMed
Bellacosa, A., Genuari, M. & Anti, M. (1996). Hereditary nonpolyposis colorectal cancer: review of clinical, molecular genetics, and counselling aspects. American Journal of Medical Genetics, 62, 353–364.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Boland, C. & Troncale, F. (1984). Familial colonie cancer without antecedent polyposis. Annals of Internal Medicine, 100, 700–701.CrossRefGoogle Scholar
Gui, E.H. & Macdonald, A.S. (2002). A Nelson-Aalen estimate of the incidence rates of Early-Onset Alzheimer's disease associated with the Presenilin-1 gene. ASTIN Bulletin, 32(1), 1–42.CrossRefGoogle Scholar
Gutiérrez, C. & Macdonald, A.S. (2003). Adult polycystic kidney disease and critical illness insurance. North American Actuarial Journal, 7(2), 93–115.CrossRefGoogle Scholar
Gutiérrez, C. & Macdonald, A.S. (2004). Huntington's disease, critical illness insurance and life insurance. Scandinavian Actuarial Journal, 2004, 279–313.Google Scholar
Hoem, J. (1988). The versatility of the Markov chain as a tool in the mathematics of life insurance. Transactions of the 23rd International Congress of Actuaries, Helsinki, S, 171–202.Google Scholar
Ionov, Y., Peinado, A., Malkhosyan, S., Shibata, D. & Perucho, M. (1993). Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonie carcinogeneisis. Nature, 363, 558–561.CrossRefGoogle Scholar
Lemaire, J., Subramanian, K., Armstrong, K. & Asch, D. (2000). Pricing term insurance in the presence of a family history of breast and ovarian cancer. North American Actuarial Journal, 4, 75–87.CrossRefGoogle Scholar
Liu, B., Parsons, R., Papadopoulos, N., Nicolaides, N., Lynch, H. & Watson, P. (1996). Analysis of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients. Natural Medicine, 2, 169–174.CrossRefGoogle Scholar
Lu, L. (2006). Some actuarial and statistical investigations into topics on genetics and insurance. Ph.D. Thesis, Heriot-Watt University, Edinburgh.Google Scholar
Lynch, H. & De la Chapelle, A. (2003). Hereditary colorectal cancer. The New England Journal of Medicine, 348, 919–932.CrossRefGoogle ScholarPubMed
Lynch, H. & Krush, A. (1971). Cancer family “G” revisited: 1895–1970. Cancer, 27, 1505–1511.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
Lynch, H. & Smyrk, T. (1996). Hereditary nonpolyposis colorectal cancer (Lynch syndrome). Cancer, 78, 1149–1167.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Macdonald, A.S. (2003a). Genetics and insurance: what we have learned so far? Scandinavian Actuarial Journal, 2003, 324–328.CrossRefGoogle Scholar
Macdonald, A.S. (2003b). Moratoria on the use of genetic tests and family history for mortgage-related life insurance. British Actuarial Journal, 9, 279–311.CrossRefGoogle Scholar
Macdonald, A.S., Waters, H.R. & Wekwete, C.T. (2003a). The genetics of breast and ovarian cancer I: a model of family history. Scandinavian Actuarial Journal, 2003, 1–27.CrossRefGoogle Scholar
Macdonald, A.S., Waters, H.R. & Wekwete, C.T. (2003b). The genetics of breast and ovarian cancer II: a model of critical illness insurance. Scandinavian Actuarial Journal, 2003, 28–50.CrossRefGoogle Scholar
Marra, G. & Boland, C. (1995). Hereditary nonpolyposis colorectal cancer: the syndrome, the genes and historical perspectives. Journal of the National Cancer Institute, 87, 1114–1125.CrossRefGoogle ScholarPubMed
Mitchell, R., Farrington, S., Dunlop, M. & Campbell, H. (2002). Mismatch repair genes hMLHl and hMSH2 and colorectal cancer: a HuGE review. American Journal of Epidemiology, 156, 885–902.CrossRefGoogle Scholar
Peltomaki, P., Lothe, R., Aaltonen, L., Pylkkanen, L., Nystromlahti, L.M. & Seruca, R. (1993). Microsatellite instability is associated with tumors that characterize the hereditary nonpolyposis colorectal carcinoma syndrome. Cancer Research, 53, 5853–5855.Google Scholar
Risinger, J., Berchuck, A., Kohler, M., Watson, P., Lynch, H. & Boyd, J. (1993). Genetic instability of microsatellites in endometrial carcinoma. Cancer Research, 53, 5100–5103.Google ScholarPubMed
Rodriguez-Bigas, M., Boland, C. & Hamilton, S. (1997). A National Cancer Institute workshop on hereditary non-polyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. Journal of the National Cancer Institute, 89, 1758–1762.CrossRefGoogle Scholar
Subramanian, K., Lemaire, J., Hershey, J., Pauly, M., Armstrong, K. & Asch, D. (1999). Estimating adverse selection costs from genetic testing for breast and ovarian cancer: the case of life insurance. Journal of Risk and Insurance, 66, 531–550.CrossRefGoogle Scholar
Thibodeau, S., Bren, G. & Schaid, D. (1993). Microsatellite instability in cancer of the proximal colon. Science, 260, 816–819.CrossRefGoogle ScholarPubMed
Vasen, A., Meckin, J. & Khan, P. (1991). The international collaborative group on hereditary non-polyposis colorectal cancer. Dis Colon Rectum, 34, 424–425.CrossRefGoogle Scholar
Vasen, H., Stormorken, A., Menko, F., Nagengast, F., Kleibeuker, J., Griffioen, G. & Taal, B. (2001). MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. Journal of Clinical Oncology, 19, 4074–4080.CrossRefGoogle ScholarPubMed
Vasen, H., Wijnen, J., Menko, F., Kleibeuker, J., Taal, B., Griffioen, G., Nagengast, F., Meijers-Heijboer, E., Bertario, L., Varesco, L., Bisgaard, M.-L., Mohr, J., Fodde, R. & Khan, P. (1996). Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology, 110, 1020–1027.CrossRefGoogle ScholarPubMed
Warthin, A. (1913). Heredity with reference to carcinoma. Archives of Internal Medicine, 12, 546–555.CrossRefGoogle Scholar