Abstract
Lynch syndrome (LS) is an autosomal dominant cancer syndrome including increased life-long risk for colorectal (CRC) and endometrial (EC) cancer, but also for cancers of other types. The risk for CRC is up to 70–80 % and for EC up to 50–60 %. Due to screening and early diagnosing the mortality related to CRC and EC seems to be low. In spite of many studies on surveillance of mutation carriers, there is no comprehensive evaluation on causes of death in LS families. The disease history and cause of death of all the deceased, tested mutation carriers and their mutation negative relatives in the Finnish LS families (N = 179) was examined utilizing hospital records and relevant national registries. Out of 1069 mutation carriers 151 had succumbed; 97 (64 %) from cancer. Out of 1146 mutation-negative family 44 members had died; 11 (25 %) of them from cancer. In 12 (7.7 %) of the deceased mutation carriers no cancer had been diagnosed. The mean age of death from cancer was 63.2 years vs. 68.8 years from non-cancer causes. Only 7.9 % of the patients with CRC had died from CRC and 5 % of those with EC, respectively. 61 % of the cancer deaths were related to extra-colonic, extra-endometrial cancers. The cumulative overall and cancer specific death rates were significantly increased in Mut+ compared to Mut− family members. Even surveillance yields decrease in the life-long risk and mortality of the most common cancers CRC and EC in LS, almost all mutation carriers will contract with cancer, and two thirds of the deceased have died from cancer. This should be taken in account in genetic counseling. Mutation carriers should be encouraged to seek help for abnormal symptoms.
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Abbreviations
- HNPCC:
-
Hereditary non-polyposis colorectal cancer
- LS:
-
Lynch syndrome
- MMR:
-
Mismatch repair
- CRC:
-
Colorectal cancer
- EC:
-
Endometrial cancer
- Mut+:
-
Tested mutation carriers
- Mut−:
-
Tested mutation-negative family member
References
Aaltonen L, Johns L, Järvinen H et al (2007) Explaining the familial colorectal cancer risk associating with mismatch repair (MMR) deficient and MMR-stable tumors. Clin Cancer Res 13:356–361
Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the international group on HNPCC. Gastroenterology 116:1453–1456
Hampel H, Stephens JA, Pukkala E et al (2005) Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology 129:415–421
Mecklin J-P, Aarnio M, Läärä E et al (2007) Development of colorectal tumors in colonoscopic surveillance in Lynch Syndrome. Gastroenterology 133:1093–1098
Järvinen HJ, Mecklin JP, Sistonen P (1995) Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 108:1405–1411
Vasen HFA, Abrdirahman M, Brohet R et al (2010) One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome. Gastroenterology 138:2300–2306
Watson P, Vasen HFH, Mecklin J-P et al (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123:444–449
Vasen HF, Wignen JT, Menko FH et al (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:1020–1027
Järvinen HJ, Renkonen-Sinisalo L, Aktan-Collan K et al (2009) Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol 27:4793–4797
Järvinen HJ et al (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118:829–834
Mecklin JP, Järvinen HJ, Peltokallio P (1986) Identification of cancer family syndrome. Gastroenterology 90:1099
Pylvänäinen K, Kairaluoma M, Mecklin J-P (2006) Compliance and satisfaction with long-term surveillance in Finnish HNPCC families. Fam Cancer 5:173–178
Parry S, Aung KW, Parry B et al (2011) Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut 60:950–957
Nieminen T, Gylling A, Abdel-Rahman WM et al (2009) Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clin Cancer Res 15:5722–5783
Burn J, Gerdes A-M, Macrae F et al (2011) Long-term effect of aspiring on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378:2081–2087
Aktan-Collan K, Haukkala A, Mecklin JP, Uutela A, Kääriäinen H (2001) Psychological consequences of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): a prospective follow-up study. Int J Cancer 93:608–611
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The study was supported by the Finnish Cancer Foundation and Central Finland Health Care District (TEVO).
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This study has been proved by Ministry of Social Affairs and Health Dnro 56/08/80.
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Pylvänäinen, K., Lehtinen, T., Kellokumpu, I. et al. Causes of death of mutation carriers in Finnish Lynch syndrome families. Familial Cancer 11, 467–471 (2012). https://doi.org/10.1007/s10689-012-9537-3
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DOI: https://doi.org/10.1007/s10689-012-9537-3