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 - 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.
N1 - Funding Information:
Recruitment, data collection, and genetic testing for the Colon Cancer Family Registry work were supported by the National Cancer Institute, National Institutes of Health under Request for Applications #CA-95-011, and through cooperative agreements with the members of the Colon Cancer Family Registry and principal investigators. The Columbus-area Hereditary Non-Polyposis Colorectal Cancer study performed by the Ohio State University Comprehensive Cancer Center was supported by grants from the National Cancer Institute, National Institutes of Health (R01-CA67941 and -CA16058). The work in Edinburgh was supported by Cancer Research UK (C348/A8896); a center grant from CORE as part of the Digestive Cancer Campaign (www.corecharity.org.uk); Medical Research Council (G0000657-53203); and Scottish Executive Chief Scientist’s Office (K/OPR/2/2/ D333). National Cancer Institute (CA67941 and CA16058 to A.d.l.c. and H.H).
PY - 2010/2
Y1 - 2010/2
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).ConclusionWe have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers. The Author 2009. Published by Oxford University Press.2010
AB - 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).ConclusionWe have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers. The Author 2009. Published by Oxford University Press.2010
UR - http://www.scopus.com/inward/record.url?scp=76349108011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76349108011&partnerID=8YFLogxK
U2 - 10.1093/jnci/djp473
DO - 10.1093/jnci/djp473
M3 - Article
C2 - 20028993
AN - SCOPUS:76349108011
SN - 0027-8874
VL - 102
SP - 193
EP - 201
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 3
ER -