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Risks of Lynch syndrome cancers for MSH6 mutation carriers.
J Natl Cancer Inst 2010; 102(3):193-201JNCI

Abstract

BACKGROUND

Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain.

METHODS

We identified 113 families of MSH6 mutation carriers from five countries that we ascertained through family cancer clinics and population-based cancer registries. Mutation status, sex, age, and histories of cancer, polypectomy, and hysterectomy were sought from 3104 of their relatives. Age-specific cumulative risks for carriers and hazard ratios (HRs) for cancer risks of carriers, compared with those of the general population of the same country, were estimated by use of a modified segregation analysis with appropriate conditioning depending on ascertainment.

RESULTS

For MSH6 mutation carriers, the estimated cumulative risks to ages 70 and 80 years, respectively, were as follows: for colorectal cancer, 22% (95% confidence interval [CI] = 14% to 32%) and 44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%) and 20% (95% CI = 11% to 35%) for women; for endometrial cancer, 26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); and for any cancer associated with Lynch syndrome, 24% (95% CI = 16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95% CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Compared with incidence for the general population, MSH6 mutation carriers had an eightfold increased incidence of colorectal cancer (HR = 7.6, 95% CI = 5.4 to 10.8), which was independent of sex and age. Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7) and a sixfold increased incidence of other cancers associated with Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7).

CONCLUSION

We have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers.

Authors+Show Affiliations

Cancer Epidemiology Centre, Victorian Cancer Registry, Carlton, Victoria, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20028993

Citation

Baglietto, Laura, et al. "Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers." Journal of the National Cancer Institute, vol. 102, no. 3, 2010, pp. 193-201.
Baglietto L, Lindor NM, Dowty JG, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102(3):193-201.
Baglietto, L., Lindor, N. M., Dowty, J. G., White, D. M., Wagner, A., Gomez Garcia, E. B., ... Jenkins, M. A. (2010). Risks of Lynch syndrome cancers for MSH6 mutation carriers. Journal of the National Cancer Institute, 102(3), pp. 193-201. doi:10.1093/jnci/djp473.
Baglietto L, et al. Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers. J Natl Cancer Inst. 2010 Feb 3;102(3):193-201. PubMed PMID: 20028993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risks of Lynch syndrome cancers for MSH6 mutation carriers. AU - Baglietto,Laura, AU - Lindor,Noralane M, AU - Dowty,James G, AU - White,Darren M, AU - Wagner,Anja, AU - Gomez Garcia,Encarna B, AU - Vriends,Annette H J T, AU - ,, AU - Cartwright,Nicola R, AU - Barnetson,Rebecca A, AU - Farrington,Susan M, AU - Tenesa,Albert, AU - Hampel,Heather, AU - Buchanan,Daniel, AU - Arnold,Sven, AU - Young,Joanne, AU - Walsh,Michael D, AU - Jass,Jeremy, AU - Macrae,Finlay, AU - Antill,Yoland, AU - Winship,Ingrid M, AU - Giles,Graham G, AU - Goldblatt,Jack, AU - Parry,Susan, AU - Suthers,Graeme, AU - Leggett,Barbara, AU - Butz,Malinda, AU - Aronson,Melyssa, AU - Poynter,Jenny N, AU - Baron,John A, AU - Le Marchand,Loic, AU - Haile,Robert, AU - Gallinger,Steve, AU - Hopper,John L, AU - Potter,John, AU - de la Chapelle,Albert, AU - Vasen,Hans F, AU - Dunlop,Malcolm G, AU - Thibodeau,Stephen N, AU - Jenkins,Mark A, Y1 - 2009/12/22/ PY - 2009/12/24/entrez PY - 2009/12/24/pubmed PY - 2010/2/26/medline SP - 193 EP - 201 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 102 IS - 3 N2 - BACKGROUND: Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain. METHODS: We identified 113 families of MSH6 mutation carriers from five countries that we ascertained through family cancer clinics and population-based cancer registries. Mutation status, sex, age, and histories of cancer, polypectomy, and hysterectomy were sought from 3104 of their relatives. Age-specific cumulative risks for carriers and hazard ratios (HRs) for cancer risks of carriers, compared with those of the general population of the same country, were estimated by use of a modified segregation analysis with appropriate conditioning depending on ascertainment. RESULTS: For MSH6 mutation carriers, the estimated cumulative risks to ages 70 and 80 years, respectively, were as follows: for colorectal cancer, 22% (95% confidence interval [CI] = 14% to 32%) and 44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%) and 20% (95% CI = 11% to 35%) for women; for endometrial cancer, 26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); and for any cancer associated with Lynch syndrome, 24% (95% CI = 16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95% CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Compared with incidence for the general population, MSH6 mutation carriers had an eightfold increased incidence of colorectal cancer (HR = 7.6, 95% CI = 5.4 to 10.8), which was independent of sex and age. Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7) and a sixfold increased incidence of other cancers associated with Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7). CONCLUSION: We have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/20028993/Risks_of_Lynch_syndrome_cancers_for_MSH6_mutation_carriers_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp473 DB - PRIME DP - Unbound Medicine ER -