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Elevated risk of prostate cancer among men with Lynch syndrome.

Abstract

PURPOSE

Prostate cancer has been described as a component tumor of Lynch syndrome (LS), with tumors obtained from mutation carriers demonstrating the DNA mismatch repair deficiency phenotype. Previous studies quantifying prostate cancer risk in LS have provided conflicting results.

METHODS

We examined cancer histories of probands and their first- through fourth-degree relatives for 198 independent mutation-positive LS families enrolled in two US familial cancer registries. Modified segregation analysis was used to calculate age-specific cumulative risk or penetrance estimates, with accompanying Wald-type CIs. Cumulative lifetime risks and hazard ratio (HR) estimates for prostate cancer were calculated and compared with those of the general population.

RESULTS

Ninety-seven cases of prostate cancer were observed in 4,127 men. Median age at prostate cancer diagnosis was 65 years (range, 38 to 89 years), with 11.53% of affected individuals diagnosed before age 50 years. The cumulative risk of prostate cancer at ages 60 and 80 years was 6.30% (95% CI, 2.47 to 9.96) and 30.0% (95% CI, 16.54 to 41.30), as compared with the population risk of 2.59% and 17.84%, respectively. The overall prostate cancer HR among carriers was 1.99 (95% CI, 1.31 to 3.03).

CONCLUSION

The cumulative lifetime risk of prostate cancer in individuals with LS is two-fold higher than in the general population and is slightly higher in carriers diagnosed before age 60 years (HR, 2.48; 95% CI, 1.34 to 4.59). These estimates are clinically valuable to quantify risk for both patients and providers.

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  • Authors+Show Affiliations

    ,

    University of Michigan, 300 North Ingalls, Ann Arbor, MI 48109-5419, USA. vraymond@umich.edu

    , , , , , , ,

    Source

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Colorectal Neoplasms, Hereditary Nonpolyposis
    DNA Mismatch Repair
    Genetic Predisposition to Disease
    Heterozygote
    Humans
    Incidence
    Male
    Middle Aged
    Odds Ratio
    Penetrance
    Prostatic Neoplasms
    Risk
    United States

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    23530095

    Citation

    Raymond, Victoria M., et al. "Elevated Risk of Prostate Cancer Among Men With Lynch Syndrome." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 31, no. 14, 2013, pp. 1713-8.
    Raymond VM, Mukherjee B, Wang F, et al. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013;31(14):1713-8.
    Raymond, V. M., Mukherjee, B., Wang, F., Huang, S. C., Stoffel, E. M., Kastrinos, F., ... Gruber, S. B. (2013). Elevated risk of prostate cancer among men with Lynch syndrome. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 31(14), pp. 1713-8. doi:10.1200/JCO.2012.44.1238.
    Raymond VM, et al. Elevated Risk of Prostate Cancer Among Men With Lynch Syndrome. J Clin Oncol. 2013 May 10;31(14):1713-8. PubMed PMID: 23530095.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Elevated risk of prostate cancer among men with Lynch syndrome. AU - Raymond,Victoria M, AU - Mukherjee,Bhramar, AU - Wang,Fei, AU - Huang,Shu-Chen, AU - Stoffel,Elena M, AU - Kastrinos,Fay, AU - Syngal,Sapna, AU - Cooney,Kathleen A, AU - Gruber,Stephen B, Y1 - 2013/03/25/ PY - 2013/3/27/entrez PY - 2013/3/27/pubmed PY - 2013/7/3/medline SP - 1713 EP - 8 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 31 IS - 14 N2 - PURPOSE: Prostate cancer has been described as a component tumor of Lynch syndrome (LS), with tumors obtained from mutation carriers demonstrating the DNA mismatch repair deficiency phenotype. Previous studies quantifying prostate cancer risk in LS have provided conflicting results. METHODS: We examined cancer histories of probands and their first- through fourth-degree relatives for 198 independent mutation-positive LS families enrolled in two US familial cancer registries. Modified segregation analysis was used to calculate age-specific cumulative risk or penetrance estimates, with accompanying Wald-type CIs. Cumulative lifetime risks and hazard ratio (HR) estimates for prostate cancer were calculated and compared with those of the general population. RESULTS: Ninety-seven cases of prostate cancer were observed in 4,127 men. Median age at prostate cancer diagnosis was 65 years (range, 38 to 89 years), with 11.53% of affected individuals diagnosed before age 50 years. The cumulative risk of prostate cancer at ages 60 and 80 years was 6.30% (95% CI, 2.47 to 9.96) and 30.0% (95% CI, 16.54 to 41.30), as compared with the population risk of 2.59% and 17.84%, respectively. The overall prostate cancer HR among carriers was 1.99 (95% CI, 1.31 to 3.03). CONCLUSION: The cumulative lifetime risk of prostate cancer in individuals with LS is two-fold higher than in the general population and is slightly higher in carriers diagnosed before age 60 years (HR, 2.48; 95% CI, 1.34 to 4.59). These estimates are clinically valuable to quantify risk for both patients and providers. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/23530095/full_citation L2 - http://ascopubs.org/doi/full/10.1200/JCO.2012.44.1238?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -