Torre Maria Luisa, Russo Giuseppina T, Ragonese Marta, Giandalia Annalisa, De Menis Ernesto, Arnaldi Giorgio, Alibrandi Angela, Buda Carmelo, Romanello Giovanni, Romeo Elisabetta L, Cucinotta Domenico, Trimarchi Francesco, Cannavo Salvatore
Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria 1, Messina, 98125, Italy,
Pituitary. 2014 Jun;17(3):257-66. doi: 10.1007/s11102-013-0499-8.
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.
We investigated the influence of MTHFR C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly.
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.
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.
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.
肢端肥大症患者发生结直肠肿瘤（CRT）的风险较高。亚甲基四氢叶酸还原酶（MTHFR）基因常见的C677T多态性是普通人群中一个有充分文献记载的CRT风险因素，但其在肢端肥大症中的作用从未被研究过。
我们研究了MTHFR C677T多态性、叶酸状态以及其他生活方式、营养和疾病特异性变量对肢端肥大症患者CRT风险的影响。
收集了115例接受全结肠镜检查的肢端肥大症患者（25例患有活动性疾病）的临床数据。评估了C677T MTHFR基因型、同型半胱氨酸、维生素B12、胰岛素生长因子和胰岛素水平以及代谢变量。
51例患者（3例腺癌）被诊断为结直肠肿瘤。MTHFR C677T分布符合哈迪-温伯格平衡，在有或无CRT的患者中相似。TT基因型患者与CRT发生之间存在相关性（斯皮尔曼检验：P = 0.03），优势比（OR）为1.32（95%可信区间0.522 - 3.362，P无统计学意义）。发现叶酸-MTHFR基因型对CRT风险有相互作用（P = 0.037）：在低叶酸亚组中，TT基因型患者发生CRT的OR比C等位基因携带者高2.4倍（95%可信区间0.484 - 11.891；P无统计学意义）。多因素分析显示，吸烟（P = 0.007）、糖化血红蛋白水平升高（P = 0.021）、血脂异常（P = 0.049）、肢端肥大症控制情况（P = 0.057）以及叶酸-MTHFR基因型相互作用（P = 0.088）与CRT相关。
在这组肢端肥大症患者中，血浆叶酸水平低的677TT MTHFR患者发生CRT的风险增加。吸烟、高糖化血红蛋白水平、血脂异常和疾病活动也与CRT风险增加相关。
