title: Lynch syndrome and cervical cancer.
abstract: Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6 and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age-specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6 fold (95% CI: 2.3-13.8; p = 0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9-10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0-46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p = 0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome.
authors.affiliation: Familial Cancer Centre, Royal Melbourne Hospital, Cabrini Health and Southern Health, Parkville, VIC, Australia.
authors.forename: Yoland C
authors.initials: YC
authors.lastname: Antill
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.affiliation: Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
authors.forename: Tina
authors.initials: T
authors.lastname: Thompson
authors.affiliation: Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.affiliation: University of Queensland Centre for Clinical Research, Royal Brisbane Hospital, Herston, Queensland, Australia.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Cummings
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.|Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.|School of Public Health, University of Washington, Seattle, WA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, CA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: James
authors.initials: J
authors.lastname: Church
authors.affiliation: Hereditary Cancer Clinic, Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Tucker
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.|Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Department of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia.|SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, SA, Australia.|School of Medicine, University of Adelaide, SA, Australia.
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.affiliation: Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC, Australia.|Department of Medicine, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Winship
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia; D002170:Canada; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009520:New Zealand; D012042:Registries; D012306:Risk; D012307:Risk Factors; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D055815:Young Adult
keywords: Lynch syndrome; cervical cancer; mismatch repair