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Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

AbstractOBJECTIVE:
To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer.
METHODS:
We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer.
RESULTS:
A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83-1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75-4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63-5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age <50 years (HR 1.48, 95% CI 1.15-1.91).
CONCLUSION:
An increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.
AuthorsRajani Bharati, Mark A Jenkins, Noralane M Lindor, Loïc Le Marchand, Steven Gallinger, Robert W Haile, Polly A Newcomb, John L Hopper, Aung Ko Win
JournalGynecologic oncology (Gynecol Oncol) Vol. 133 Issue 2 Pg. 287-92 (May 2014) ISSN: 1095-6859 [Electronic] United States
PMID24631449 (Publication Type: Journal Article)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Colorectal Neoplasms (genetics)
  • DNA Mismatch Repair (genetics)
  • Endometrial Neoplasms (genetics)
  • Family Health
  • Female
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Infant
  • Middle Aged
  • Regression Analysis
  • Retrospective Studies
  • Young Adult

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