Cabrera-Mulero Amanda, Crujeiras Ana B, Izquierdo Andrea G, Torres Esperanza, Ayers Duncan, Casanueva Felipe F, Tinahones Francisco J, Morcillo Sonsoles, Macias-Gonzalez Manuel
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Málaga, Spain.
CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition CB06/03/0018), "Instituto de Salud Carlos III", 28029 Madrid, Spain.
J Clin Med. 2019 Jul 17;8(7):1041. doi: 10.3390/jcm8071041.
The relationship between body weight and different cancers is now well-recognized and among such cancers, colorectal cancer (CRC) is reported most frequently. Our group recently published findings, through an epigenome-wide association study, suggesting that body mass index (BMI) could act as a relevant risk factor in the CRC. In addition, aberrant methylation is one of the major mechanisms for Wnt signaling activation in CRC. Conversely, neoadjuvant chemo-radiotherapy appears to alter the rectal cancer epigenome. This study was aimed to evaluate the effect of obesity, measured by BMI, on the methylation of in tumor samples of patients with CRC. Non-treated CRC patients and CRC patients treated with pre-operative neoadjuvant therapy from 2011 to 2013 were included and classified by BMI < 25.0 kg/m and BMI > 25.0 kg/m. DNA methylation in tumor samples was measured by pyrosequencing. Our findings suggest a possible interaction between methylation levels and BMI in CRC tumor samples. The correlation of hypomethylation with an elevated BMI was stronger within the non-treated CRC patient group than within the treated CRC patient group. We have successfully demonstrated that the beneficial association of tumor hypomethylation is dependent on patient BMI in non-treated CRC, suggesting a possible tumor suppressor role for in overweight and obese patients. Additional studies of clinical pathologies would be necessary to strengthen these preliminary results.
体重与不同癌症之间的关系现已得到充分认识，在这类癌症中，结直肠癌（CRC）的报道最为频繁。我们团队最近通过一项全表观基因组关联研究发表了研究结果，表明体重指数（BMI）可能是结直肠癌的一个相关风险因素。此外，异常甲基化是结直肠癌中Wnt信号激活的主要机制之一。相反，新辅助放化疗似乎会改变直肠癌的表观基因组。本研究旨在评估以BMI衡量的肥胖对结直肠癌患者肿瘤样本中甲基化的影响。纳入了2011年至2013年未接受治疗的结直肠癌患者和接受术前新辅助治疗的结直肠癌患者，并根据BMI<25.0 kg/m²和BMI>25.0 kg/m²进行分类。通过焦磷酸测序测量肿瘤样本中的DNA甲基化。我们的研究结果表明，结直肠癌肿瘤样本中甲基化水平与BMI之间可能存在相互作用。在未治疗的结直肠癌患者组中，甲基化水平降低与BMI升高之间的相关性比治疗后的结直肠癌患者组更强。我们已经成功证明，在未治疗的结直肠癌中，肿瘤甲基化水平降低的有益关联取决于患者的BMI，这表明在超重和肥胖患者中可能具有肿瘤抑制作用。需要进行更多的临床病理学研究来加强这些初步结果。
