PURPOSE: Increased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study. PATIENTS AND METHODS: Factor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression. RESULTS: Homozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk. CONCLUSION: Our results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.
PURPOSE: Increased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study. PATIENTS AND METHODS: Factor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression. RESULTS: Homozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk. CONCLUSION: Our results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.
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Authors: Melanie M Ivancic; Edward L Huttlin; Xiaodi Chen; Jennifer K Pleiman; Amy A Irving; Adrian D Hegeman; William F Dove; Michael R Sussman Journal: J Proteome Res Date: 2013-08-08 Impact factor: 4.466
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Authors: Iona Cheng; Jonathan M Kocarnik; Logan Dumitrescu; Noralane M Lindor; Jenny Chang-Claude; Christy L Avery; Christian P Caberto; Shelly-Ann Love; Martha L Slattery; Andrew T Chan; John A Baron; Lucia A Hindorff; Sungshim Lani Park; Fredrick R Schumacher; Michael Hoffmeister; Peter Kraft; Anne M Butler; David J Duggan; Lifang Hou; Chris S Carlson; Kristine R Monroe; Yi Lin; Cara L Carty; Sue Mann; Jing Ma; Edward L Giovannucci; Charles S Fuchs; Polly A Newcomb; Mark A Jenkins; John L Hopper; Robert W Haile; David V Conti; Peter T Campbell; John D Potter; Bette J Caan; Robert E Schoen; Richard B Hayes; Stephen J Chanock; Sonja I Berndt; Sebastien Küry; Stephane Bézieau; Jose Luis Ambite; Gowri Kumaraguruparan; Danielle M Richardson; Robert J Goodloe; Holli H Dilks; Paxton Baker; Brent W Zanke; Mathieu Lemire; Steven Gallinger; Li Hsu; Shuo Jiao; Tabitha A Harrison; Daniela Seminara; Christopher A Haiman; Charles Kooperberg; Lynne R Wilkens; Carolyn M Hutter; Emily White; Dana C Crawford; Gerardo Heiss; Thomas J Hudson; Hermann Brenner; William S Bush; Graham Casey; Loïc Le Marchand; Ulrike Peters Journal: Gut Date: 2013-08-09 Impact factor: 23.059
Authors: F S Falvella; C Cremolini; R Miceli; F Nichetti; S Cheli; C Antoniotti; G Infante; A Martinetti; F Marmorino; E Sottotetti; R Berenato; M Caporale; A Colombo; F de Braud; M Di Bartolomeo; E Clementi; F Loupakis; F Pietrantonio Journal: Pharmacogenomics J Date: 2016-03-22 Impact factor: 3.550