BACKGROUND: Acromegalic patients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene is a well-documented CRT risk factor in the general population, but its role in acromegaly has never been examined. PURPOSE: We investigated the influence of MTHFR C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly. METHODS: Clinical data were collected from 115 acromegalic patients (25 with active disease) who underwent a complete colonoscopy. C677T MTHFR genotype, homocysteine, vitamin B12, insulin growth factor and insulin levels, as well as metabolic variables were evaluated. RESULTS: Colorectal tumours were identified in 51 patients (3 adenocarcinomas). MTHFR C677T distribution was in the Hardy-Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman's test: P = 0.03), with an Odds Ratio (OR) of 1.32 (95% CI 0.522-3.362, P NS). A folate-MTHFR genotype interaction on CRT risk was found (P = 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95% CI 0.484-11.891; P NS) than C-allele carriers. Smoking (P = 0.007), increased HbA1c levels (P = 0.021), dyslipidaemia (P = 0.049), acromegaly control (P = 0.057), and folate-MTHFR genotype interaction (P = 0.088) were associated with CRT at multivariate analysis. CONCLUSIONS: In this cohort of acromegalic patients, CRT risk is increased in 677TT MTHFR patients with low plasma folate levels. Smoking, high HbA1c levels, dyslipidaemia and disease activity were also associated with increased CRT risk.
BACKGROUND:Acromegalicpatients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene is a well-documented CRT risk factor in the general population, but its role in acromegaly has never been examined. PURPOSE: We investigated the influence of MTHFRC677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly. METHODS: Clinical data were collected from 115 acromegalicpatients (25 with active disease) who underwent a complete colonoscopy. C677TMTHFR genotype, homocysteine, vitamin B12, insulin growth factor and insulin levels, as well as metabolic variables were evaluated. RESULTS:Colorectal tumours were identified in 51 patients (3 adenocarcinomas). MTHFRC677T distribution was in the Hardy-Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman's test: P = 0.03), with an Odds Ratio (OR) of 1.32 (95% CI 0.522-3.362, P NS). A folate-MTHFR genotype interaction on CRT risk was found (P = 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95% CI 0.484-11.891; P NS) than C-allele carriers. Smoking (P = 0.007), increased HbA1c levels (P = 0.021), dyslipidaemia (P = 0.049), acromegaly control (P = 0.057), and folate-MTHFR genotype interaction (P = 0.088) were associated with CRT at multivariate analysis. CONCLUSIONS: In this cohort of acromegalicpatients, CRT risk is increased in 677TT MTHFRpatients with low plasma folate levels. Smoking, high HbA1c levels, dyslipidaemia and disease activity were also associated with increased CRT risk.
Authors: A Colao; G Arnaldi; P Beck-Peccoz; S Cannavò; R Cozzi; E degli Uberti; L De Marinis; E De Menis; D Ferone; V Gasco; A Giustina; S Grottoli; G Lombardi; P Maffei; E Martino; F Minuto; R Pivonello; E Ghigo Journal: J Endocrinol Invest Date: 2007-09 Impact factor: 4.256
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Authors: Jian Gong; Carolyn Hutter; John A Baron; Sonja Berndt; Bette Caan; Peter T Campbell; Graham Casey; Andrew T Chan; Michelle Cotterchio; Charles S Fuchs; Steven Gallinger; Edward Giovannucci; Tabitha Harrison; Richard Hayes; Li Hsu; Shuo Jiao; Yi Lin; Noralane M Lindor; Polly Newcomb; Bethann Pflugeisen; Amanda I Phipps; Thomas Rohan; Robert Schoen; Daniela Seminara; Martha L Slattery; Deanna Stelling; Fridtjof Thomas; Greg Warnick; Emily White; John Potter; Ulrike Peters Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-09-20 Impact factor: 4.254