Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene

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• 作者：Aung Ko Win ; Jeanette C. Reece ; Daniel D. Buchanan ; Mark Clendenning…
• 关键词：MUTYH ; Mismatch repair ; Colorectal cancer ; Lynch syndrome
• 刊名：Familial Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：14
• 期：4
• 页码：575-583
• 全文大小：440 KB
• 参考文献：1.Win AK, Young JP, Lindor NM et al (2012) Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol 30(9):958-64PubMedCentral CrossRef PubMed
  2.Lynch HT, de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348(10):919-32CrossRef PubMed
  3.Win AK, Cleary SP, Dowty JG et al (2011) Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. Int J Cancer 129(9):2256-262PubMedCentral CrossRef PubMed
  4.Win AK, Dowty JG, Cleary SP et al (2014) Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology 146(5):1208-211PubMedCentral CrossRef PubMed
  5.Jenkins MA, Croitoru ME, Monga N et al (2006) Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol Biomarkers Prev 15(2):312-14CrossRef PubMed
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  11.Chen J, Pande M, Huang YJ et al (2013) Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients. Carcinogenesis 34(2):299-06PubMedCentral CrossRef PubMed
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  13.Frazier ML, O’Donnell FT, Kong S et al (2001) Age-associated risk of cancer among individuals with N-acetyltransferase 2 (NAT2) mutations and mutations in DNA mismatch repair genes. Cancer Res 61(4):1269-271PubMed
  14.Kong S, Amos CI, Luthra R, Lynch PM, Levin B, Frazier ML (2000) Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer. Cancer Res 60(2):249-52PubMed
  15.Win AK, Hopper JL, Buchanan DD et al (2013) Are the common genetic variants known to be associated with colorectal cancer risk in the general population also associated with colorectal cancer risk for DNA mismatch repair gene mutation carriers? Eur J Cancer 49(7):1578-587PubMedCentral CrossRef PubMed
  16.Gu Y, Parker A, Wilson TM, Bai H, Chang D-Y, Lu AL (2002) Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6. J Biol Chem 277(13):11135-1142CrossRef PubMed
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  23.Gorgens H, Kruger S, Kuhlisch E et al (2006) Microsatellite stable colorectal cancers in cli
• 作者单位：Aung Ko Win (1)
  Jeanette C. Reece (1)
  Daniel D. Buchanan (1) (2)
  Mark Clendenning (2)
  Joanne P. Young (3) (4) (5)
  Sean P. Cleary (6)
  Hyeja Kim (6)
  Michelle Cotterchio (7)
  James G. Dowty (1)
  Robert J. MacInnis (1) (8)
  Katherine M. Tucker (9)
  Ingrid M. Winship (10) (11)
  Finlay A. Macrae (11) (12)
  Terrilea Burnett (13)
  Lo?c Le Marchand (13)
  Graham Casey (14)
  Robert W. Haile (15)
  Polly A. Newcomb (16) (17)
  Stephen N. Thibodeau (18)
  Noralane M. Lindor (19)
  John L. Hopper (1) (20)
  Steven Gallinger (6)
  Mark A. Jenkins (1)
  
  1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Level 3, 207 Bouverie Street, Parkville, VIC, 3010, Australia
  2. Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia
  3. Department of Oncology, The Queen Elizabeth Hospital, Woodville, SA, Australia
  4. SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, SA, Australia
  5. School of Medicine, University of Adelaide, Adelaide, SA, Australia
  6. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
  7. Cancer Care Ontario, Toronto, ON, Canada
  8. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia
  9. Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, NSW, Australia
  10. Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC, Australia
  11. Department of Medicine, The University of Melbourne, Parkville, VIC, Australia
  12. Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, VIC, Australia
  13. University of Hawaii Cancer Center, Honolulu, HI, USA
  14. Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
  15. Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, USA
  16. School of Public Health, University of Washington, Seattle, WA, USA
  17. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  18. Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  19. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA
  20. Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Human Genetics
  Epidemiology
  
• 出版者：Springer Netherlands
• ISSN：1573-7292

文摘

The base excision repair protein, MUTYH, functionally interacts with the DNA mismatch repair (MMR) system. As genetic testing moves from testing one gene at a time, to gene panel and whole exome next generation sequencing approaches, understandin g the risk associated with co-existence of germline mutations in these genes will be important for clinical interpretation and management. From the Colon Cancer Family Registry, we identified 10 carriers who had both a MUTYH mutation (6 with c.1187G>A p.(Gly396Asp), 3 with c.821G>A p.(Arg274Gln), and 1 with c.536A>G p.(Tyr179Cys)) and a MMR gene mutation (3 in MLH1, 6 in MSH2, and 1 in PMS2), 375 carriers of a single (monoallelic) MUTYH mutation alone, and 469 carriers of a MMR gene mutation alone. Of the 10 carriers of both gene mutations, 8 were diagnosed with colorectal cancer. Using a weighted cohort analysis, we estimated that risk of colorectal cancer for carriers of both a MUTYH and a MMR gene mutation was substantially higher than that for carriers of a MUTYH mutation alone [hazard ratio (HR) 21.5, 95 % confidence interval (CI) 9.19-0.1; p < 0.001], but not different from that for carriers of a MMR gene mutation alone (HR 1.94, 95 % CI 0.63-.99; p = 0.25). Within the limited power of this study, there was no evidence that a monoallelic MUTYH gene mutation confers additional risk of colorectal cancer for carriers of a MMR gene mutation alone. Our finding suggests MUTYH mutation testing in MMR gene mutation carriers is not clinically informative. Keywords MUTYH Mismatch repair Colorectal cancer Lynch syndrome