Abstract：
BACKGROUND: Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway.
METHODS: We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010-2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR).
RESULTS: We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84].
CONCLUSIONS: In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP.
METHODS: We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010-2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR).
RESULTS: We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84].
CONCLUSIONS: In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP.
摘要：
背景：锯齿状病变和息肉（SP）是通过锯齿状途径的多达30％的结直肠癌（CRC）的前体。这通常需要早期BRAF突变和MLH1超甲基化,导致错配修复缺陷(dMMR)CRC。我们调查了同时发生CRC和SP的患者中dMMRCRC的预测因子，以增加我们对锯齿状途径的了解。
方法：我们使用了2010-2021年期间丹麦病理学登记处和丹麦结直肠癌组数据库的数据来调查dMMRCRC发展的危险因素。我们使用逻辑回归模型来确定与具有熟练MMR（pMMR）的CRC相比，发展dMMRCRC的危险因素的差异。
结果：我们纳入了3273例患者，中位年龄为70.7岁[64.3,76.4]，其中1850例（56.5％）为男性。dMMRCRC在592例患者中存在（18.1%），MLH1/PMS2的损失是最常见的。女性患dMMRCRC的风险显著高于3.47[2.87;4.20]。当调整年龄时，SP亚型,常规腺瘤（CA），解剖位置和生活方式因素，女性仍然是最强的预测因子OR2.84[2.27;3.56]。无柄锯齿状病变伴或不伴发育不良的存在分别与较高风险OR1.60[1.11;2.31]和OR1.42[1.11;1.82]有关，而常规腺瘤构成较低风险OR0.68[0.55;0.84]。
结论：总之，我们发现在SP患者中，女性与dMMRCRC相关性最强的几个预测因子。
方法：我们使用了2010-2021年期间丹麦病理学登记处和丹麦结直肠癌组数据库的数据来调查dMMRCRC发展的危险因素。我们使用逻辑回归模型来确定与具有熟练MMR（pMMR）的CRC相比，发展dMMRCRC的危险因素的差异。
结果：我们纳入了3273例患者，中位年龄为70.7岁[64.3,76.4]，其中1850例（56.5％）为男性。dMMRCRC在592例患者中存在（18.1%），MLH1/PMS2的损失是最常见的。女性患dMMRCRC的风险显著高于3.47[2.87;4.20]。当调整年龄时，SP亚型,常规腺瘤（CA），解剖位置和生活方式因素，女性仍然是最强的预测因子OR2.84[2.27;3.56]。无柄锯齿状病变伴或不伴发育不良的存在分别与较高风险OR1.60[1.11;2.31]和OR1.42[1.11;1.82]有关，而常规腺瘤构成较低风险OR0.68[0.55;0.84]。
结论：总之，我们发现在SP患者中，女性与dMMRCRC相关性最强的几个预测因子。
