性别差异在代谢-人体测量表型与肥胖相关癌症风险关系中的作用：一项前瞻性队列研究

Sex disparity in the association between metabolic-anthropometric phenotypes and risk of obesity-related cancer: a prospective cohort study

BMC Medicine

影响因子:8.3

分区:医学1区 Top / 医学：内科1区

发表日期:2024 Sep 02

作者: Jianxiao Gong, Fubin Liu, Yu Peng, Peng Wang, Changyu Si, Xixuan Wang, Huijun Zhou, Jiale Gu, Ailing Qin, Fangfang Song

DOI: 10.1186/s12916-024-03592-9

摘要

代谢性肥胖（由体质指数BMI定义）表型与肥胖相关癌症（ORC）之间的性别差异仍不清楚。考虑到BMI反映整体肥胖但不反映脂肪分布，我们旨在系统评估我们新提出的代谢-人体测量表型与全身及特定部位癌症风险的关系，并分析性别差异。共纳入来自英国生物库的141,579名男性（平均年龄：56.37岁，随访时间：12.04年）和131,047名女性（平均年龄：56.22岁，随访时间：11.82年），根据代谢状态（健康/不健康）、BMI（非肥胖/肥胖）和体型（梨型/瘦型/苹果型/宽体型）划分为代谢-人体测量表型。通过Cox比例风险回归模型，计算不同表型与全身及部位特异性癌症的风险比（HR）及95%置信区间（CI），评估性别差异。结果显示，不健康代谢和/或肥胖表型在男性中比在女性中更易引起全身及结直肠癌的较高风险（相较健康非肥胖表型，P交互<0.05）。值得注意的是，健康代谢性肥胖表型在男性中显著增加多种癌症风险（HR：1.58〜2.91），而在女性中仅与子宫内膜癌（HR=1.89，95% CI：1.54-2.32）和绝经后乳腺癌风险升高相关（HR=1.17，95% CI：1.05-1.31）。类似地，即使在健康代谢状态下，男性携带苹果型和宽体型（健康苹果/宽体型和健康非肥胖苹果/宽体型）也表现出较高的癌症风险（主要包括结直肠、肝脏、胃贲门和肾脏癌，HR：1.20〜3.81），相比梨型或非肥胖梨型。研究发现，代谢-人体测量表型与癌症风险之间存在显著的性别差异。建议未来的癌症预防控制应考虑体型和性别差异。

Abstract

Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex.A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models.We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape.There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.