欧洲癌症与营养前瞻性调查（EPIC）中代谢定义的体型表型与子宫内膜癌风险
Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).
作者信息
Kliemann Nathalie, Ould Ammar Romain, Biessy Carine, Gicquiau Audrey, Katzke Verena, Kaaks Rudolf, Tjønneland Anne, Olsen Anja, Sánchez Maria-Jose, Crous-Bou Marta, Pasanisi Fabrizio, Tin Tin Sandar, Perez-Cornago Aurora, Aune Dagfinn, Christakoudi Sofia, Heath Alicia K, Colorado-Yohar Sandra M, Grioni Sara, Skeie Guri, Sartor Hanna, Idahl Annika, Rylander Charlotta, May Anne M, Weiderpass Elisabete, Freisling Heinz, Playdon Mary C, Rinaldi Sabina, Murphy Neil, Huybrechts Inge, Dossus Laure, Gunter Marc J
机构信息
International Agency for Research on Cancer, Lyon, France.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
出版信息
Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1359-1367. doi: 10.1158/1055-9965.EPI-22-0160.
BACKGROUND
Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known.
METHODS
The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case-control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW.
RESULTS
In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05-2.10 and ORWHR, 1.68; 95% CI, 1.21-2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73-3.27; ORWC, 2.69; 95% CI, 1.92-3.77 and ORWHR, 1.83; 95% CI, 1.32-2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24-3.04).
CONCLUSIONS
Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin.
IMPACT
Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.
背景
肥胖是子宫内膜癌的一个风险因素，但代谢功能障碍是否独立于体型与子宫内膜癌相关尚不清楚。
方法
在欧洲癌症与营养前瞻性调查（EPIC）中的一项巢式病例对照研究（817例病例/817例对照）中，研究了代谢定义的体型表型与子宫内膜癌风险的关联。使用C肽浓度来定义对照参与者中的代谢健康（MH；<第1三分位数）和代谢不健康（MU；≥第1三分位数）状态。这些代谢健康定义与正常体重（NW；体重指数（BMI）<25 kg/m2或腰围（WC）<80 cm或腰臀比（WHR）<0.8）和超重（OW；BMI≥25 kg/m2或WC≥80 cm或WHR≥0.8）状态相结合，为每种人体测量指标生成四个表型组：（i）MH/NW，（ii）MH/OW，（iii）MU/NW，和（iv）MU/OW。
结果
在多变量调整的条件逻辑回归模型中，与MH/NW个体相比，被归类为MU/NW的个体患子宫内膜癌的风险更高[基于WC的比值比（ORWC），1.48；95%置信区间（CI），1.05 - 2.10；基于WHR的OR，1.68；95% CI，1.21 - 2.35]以及MU/OW个体（基于BMI的OR，2.38；95% CI，1.73 - 3.27；基于WC的ORWC，2.69；95% CI，1.92 - 3.77；基于WHR的OR，1.83；95% CI，1.32 - 2.54）。与MH/NW个体相比，MH/OW个体患子宫内膜癌的风险也增加（基于WC的ORWC，1.94；95% CI，1.24 - 3.04）。
结论
无论体型如何，代谢功能障碍的女性患子宫内膜癌的风险似乎更高。然而，即使在胰岛素水平较低的女性中，超重状态也会增加子宫内膜癌风险, 这表明肥胖相关途径在该癌症发生发展中的作用超出了胰岛素。
影响
按代谢健康对女性进行分类，在识别子宫内膜癌高风险人群方面可能比单纯的人体测量更有用。
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