TY - JOUR
T1 - Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers
AU - Dutch Lynch Syndrome Study Grp
AU - Baglietto, Laura
AU - Lindor, Noralane M.
AU - Dowty, James G.
AU - White, Darren M.
AU - Wagner, Anja
AU - Garcia, Encarna B. Gomez
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.
PY - 2010/2/3
Y1 - 2010/2/3
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.
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).Conclusion We have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers.
UR - https://www.scopus.com/pages/publications/76349108011
U2 - 10.1093/jnci/djp473
DO - 10.1093/jnci/djp473
M3 - Article
C2 - 20028993
SN - 0027-8874
VL - 102
SP - 193
EP - 201
JO - Journal of the National Cancer Institute (JNCI)
JF - Journal of the National Cancer Institute (JNCI)
IS - 3
ER -