PURPOSE: CHEK2*1100delC heterozygosity has been associated with increased risk of breast, prostate, and colorectal cancer in case-control studies. We tested the hypothesis that CHEK2*1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorectal cancer in particular. PATIENTS AND METHODS: We performed a prospective study of 9,231 individuals from the Danish general population, who were observed for 34 years, and we performed a case-control study including 1,101 cases of breast cancer and 4,665 controls. RESULTS: Of the general population, 0.5% were heterozygotes and 99.5% were noncarriers. In the prospective study, multifactorially adjusted hazard ratios by CHEK2*1100delC heterozygosity versus noncarriers were 1.2 (95% CI, 0.7 to 2.1) for all cancers, 3.2 (95% CI, 1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6 (95% CI, 0.4 to 6.5) for colorectal cancer. In the case-control study, age-matched odds ratio for breast cancer by CHEK2*1100delC heterozygosity versus noncarriers was 2.6 (95% CI, 1.3 to 5.4). The absolute 10-year risk of breast cancer in CHEK2*1100delC heterozygotes amounted to 24% in women older than 60 years undergoing hormone replacement therapy, with a body mass index of 25 kg/m2 or higher. CONCLUSION: CHEK2*1100delC heterozygosity is associated with a three-fold risk of breast cancer in women in the general population.
PURPOSE:CHEK2*1100delC heterozygosity has been associated with increased risk of breast, prostate, and colorectal cancer in case-control studies. We tested the hypothesis that CHEK2*1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorectal cancer in particular. PATIENTS AND METHODS: We performed a prospective study of 9,231 individuals from the Danish general population, who were observed for 34 years, and we performed a case-control study including 1,101 cases of breast cancer and 4,665 controls. RESULTS: Of the general population, 0.5% were heterozygotes and 99.5% were noncarriers. In the prospective study, multifactorially adjusted hazard ratios by CHEK2*1100delC heterozygosity versus noncarriers were 1.2 (95% CI, 0.7 to 2.1) for all cancers, 3.2 (95% CI, 1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6 (95% CI, 0.4 to 6.5) for colorectal cancer. In the case-control study, age-matched odds ratio for breast cancer by CHEK2*1100delC heterozygosity versus noncarriers was 2.6 (95% CI, 1.3 to 5.4). The absolute 10-year risk of breast cancer in CHEK2*1100delC heterozygotes amounted to 24% in women older than 60 years undergoing hormone replacement therapy, with a body mass index of 25 kg/m2 or higher. CONCLUSION:CHEK2*1100delC heterozygosity is associated with a three-fold risk of breast cancer in women in the general population.
Authors: Roger L Milne; Justo Lorenzo-Bermejo; Barbara Burwinkel; Núria Malats; Jose Ignacio Arias; M Pilar Zamora; Javier Benítez; Manjeet K Humphreys; Montserrat García-Closas; Stephen J Chanock; Jolanta Lissowska; Mark E Sherman; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Heli Nevanlinna; Tuomas Heikkinen; Kristiina Aittomäki; Carl Blomqvist; Hoda Anton-Culver; Argyrios Ziogas; Peter Devilee; Christie J van Asperen; Rob A E M Tollenaar; Caroline Seynaeve; Per Hall; Kamila Czene; Jianjun Liu; Astrid K Irwanto; Daehee Kang; Keun-Young Yoo; Dong-Young Noh; Fergus J Couch; Janet E Olson; Xianshu Wang; Zachary Fredericksen; Børge G Nordestgaard; Stig E Bojesen; Henrik Flyger; Sara Margolin; Annika Lindblom; Peter A Fasching; Ruediger Schulz-Wendtland; Arif B Ekici; Matthias W Beckmann; Shan Wang-Gohrke; Chen-Yang Shen; Jyh-Cherng Yu; Huan-Ming Hsu; Pei-Ei Wu; Graham G Giles; Gianluca Severi; Laura Baglietto; Dallas R English; Angela Cox; Ian Brock; Graeme Elliott; Malcolm W R Reed; Jonathan Beesley; Xiaoqing Chen; Kconfab Investigators; Olivia Fletcher; Lorna Gibson; Isabel dos Santos Silva; Julian Peto; Bernd Frank; Joerg Heil; Alfons Meindl; Jenny Chang-Claude; Rebecca Hein; Alina Vrieling; Dieter Flesch-Janys; Melissa C Southey; Letitia Smith; Carmel Apicella; John L Hopper; Alison M Dunning; Karen A Pooley; Paul D P Pharoah; Ute Hamann; Beate Pesch; Yon-Dschun Ko; Douglas F Easton; Georgia Chenevix-Trench Journal: J Med Genet Date: 2011-10 Impact factor: 6.318
Authors: Magdalena Stawinska; Adam Cygankiewicz; Radzislaw Trzcinski; Michal Mik; Adam Dziki; Wanda M Krajewska Journal: Int J Colorectal Dis Date: 2008-08-05 Impact factor: 2.571
Authors: Daphne W Bell; Sang H Kim; Andrew K Godwin; Taryn A Schiripo; Patricia L Harris; Sara M Haserlat; Doke C R Wahrer; Christopher A Haiman; Mary B Daly; Kristin B Niendorf; Matthew R Smith; Dennis C Sgroi; Judy E Garber; Olufunmilayo I Olopade; Loic Le Marchand; Brian E Henderson; David Altshuler; Daniel A Haber; Matthew L Freedman Journal: Int J Cancer Date: 2007-12-15 Impact factor: 7.396