Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma

Andreas Obermair, Danny R. Youlden, Joanne P. Young, Noralane Morey Lindor, John A. Baron, Polly Newcomb, Susan Parry, John L. Hopper, Robert Haile, Mark A. Jenkins

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Abstract

The risk of endometrial cancer (EC) subsequent to a diagnosis of colorectal cancer in women with a germline mutation in a mismatch repair gene [Lynch syndrome or hereditary non-polyposis colon cancer (HNPCC)] is unknown. We estimated the risk of EC following a diagnosis of colorectal carcinoma (CRC) for women with Lynch syndrome. A retrospective cohort study was performed on women diagnosed with CRC with a germline mutation in a mismatch repair (MMR) gene (Lynch syndrome cases), and women with microsatellite stable (MSS) CRC who were not known to carry a germline mutation (non-Lynch cases), identified from the Colon Cancer Family Registry. The incidence of EC following CRC was estimated and compared for women with and without Lynch syndrome, using adjusted hazards ratios calculated for time at risk among each group. A total of 112 women with Lynch syndrome and a previous diagnosis of CRC were compared with 908 women without Lynch and with a MSS CRC diagnosis. The estimated 10-year cumulative risk of EC subsequent to CRC was 23.4% [95% confidence interval (CI): 15-36%] for Lynch syndrome women compared with 1.6% (95% CI: 0.7-3.8%) for non-Lynch women. After adjusting for ascertainment, age at diagnosis and diagnosis of other cancers, risk of subsequent diagnosis with EC was elevated sixfold in women with Lynch syndrome compared with non-Lynch women (HR 6.2; 95% CI 2.2-17.3; p = 0.001). Approximately one quarter of women diagnosed with Lynch syndrome-associated CRC developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women.

Original languageEnglish (US)
Pages (from-to)2678-2684
Number of pages7
JournalInternational Journal of Cancer
Volume127
Issue number11
DOIs
StatePublished - Dec 1 2010

Fingerprint

Endometrial Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Germ-Line Mutation
DNA Mismatch Repair
Confidence Intervals
Microsatellite Repeats
Genes
Registries
Neoplasms
Cohort Studies
Retrospective Studies

Keywords

  • endometrial cancer
  • epidemiology
  • Lynch syndrome
  • risk assessment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Obermair, A., Youlden, D. R., Young, J. P., Lindor, N. M., Baron, J. A., Newcomb, P., ... Jenkins, M. A. (2010). Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. International Journal of Cancer, 127(11), 2678-2684. https://doi.org/10.1002/ijc.25501

Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. / Obermair, Andreas; Youlden, Danny R.; Young, Joanne P.; Lindor, Noralane Morey; Baron, John A.; Newcomb, Polly; Parry, Susan; Hopper, John L.; Haile, Robert; Jenkins, Mark A.

In: International Journal of Cancer, Vol. 127, No. 11, 01.12.2010, p. 2678-2684.

Research output: Contribution to journalArticle

Obermair, A, Youlden, DR, Young, JP, Lindor, NM, Baron, JA, Newcomb, P, Parry, S, Hopper, JL, Haile, R & Jenkins, MA 2010, 'Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma', International Journal of Cancer, vol. 127, no. 11, pp. 2678-2684. https://doi.org/10.1002/ijc.25501
Obermair, Andreas ; Youlden, Danny R. ; Young, Joanne P. ; Lindor, Noralane Morey ; Baron, John A. ; Newcomb, Polly ; Parry, Susan ; Hopper, John L. ; Haile, Robert ; Jenkins, Mark A. / Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. In: International Journal of Cancer. 2010 ; Vol. 127, No. 11. pp. 2678-2684.
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abstract = "The risk of endometrial cancer (EC) subsequent to a diagnosis of colorectal cancer in women with a germline mutation in a mismatch repair gene [Lynch syndrome or hereditary non-polyposis colon cancer (HNPCC)] is unknown. We estimated the risk of EC following a diagnosis of colorectal carcinoma (CRC) for women with Lynch syndrome. A retrospective cohort study was performed on women diagnosed with CRC with a germline mutation in a mismatch repair (MMR) gene (Lynch syndrome cases), and women with microsatellite stable (MSS) CRC who were not known to carry a germline mutation (non-Lynch cases), identified from the Colon Cancer Family Registry. The incidence of EC following CRC was estimated and compared for women with and without Lynch syndrome, using adjusted hazards ratios calculated for time at risk among each group. A total of 112 women with Lynch syndrome and a previous diagnosis of CRC were compared with 908 women without Lynch and with a MSS CRC diagnosis. The estimated 10-year cumulative risk of EC subsequent to CRC was 23.4{\%} [95{\%} confidence interval (CI): 15-36{\%}] for Lynch syndrome women compared with 1.6{\%} (95{\%} CI: 0.7-3.8{\%}) for non-Lynch women. After adjusting for ascertainment, age at diagnosis and diagnosis of other cancers, risk of subsequent diagnosis with EC was elevated sixfold in women with Lynch syndrome compared with non-Lynch women (HR 6.2; 95{\%} CI 2.2-17.3; p = 0.001). Approximately one quarter of women diagnosed with Lynch syndrome-associated CRC developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women.",
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