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在 CLUE II 队列中,诊断前循环脂肪因子与结直肠癌和腺瘤之间的关联。

Association between pre-diagnostic circulating adipokines and colorectal cancer and adenoma in the CLUE II cohort.

机构信息

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Rm. E6133, Baltimore, MD, 21205, USA.

Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins, Baltimore, MD, USA.

出版信息

Cancer Causes Control. 2021 Aug;32(8):871-881. doi: 10.1007/s10552-021-01441-1. Epub 2021 May 17.

Abstract

OBJECTIVE

Obesity is a known risk factor for colorectal cancer (CRC) and adenoma. Obese individuals have higher circulating concentrations of certain endocrine and immune factors produced by adipocytes thought to partially underlie the association between obesity and colorectal neoplasia. Thus, we evaluated the association of plasma concentrations of adiponectin, leptin, and soluble tumor necrosis factor receptor-2 (sTNFR2) with CRC and adenoma.

METHODS

We ascertained 193 CRC cases and 193 matched controls, and 131 colorectal adenoma cases and 131 matched controls who had had an endoscopy nested in the CLUE II cohort of Washington County, MD. Plasma markers were measured using ELISA. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression for quartiles of the plasma markers separately for CRC and adenoma.

RESULTS

Adjusting for leptin and adiponectin, sTNFR2 was positively associated with CRC only in men (Q4 vs. Q1: OR = 3.14, 95% CI 1.11-8.86), which was unchanged adjusting for BMI (3.46, 95% CI 1.19-10.06). Leptin and adiponectin were not associated with CRC risk overall or in men or women. Adiponectin, leptin, and sTNFR2 were not associated with adenoma risk overall or in men or women.

CONCLUSION

In this study, leptin and adiponectin were not associated with colorectal carcinogenesis and thus do not appear to underlie the association between obesity and colorectal carcinogenesis. sTNFR2, which we measured as a correlate of TNF-α, was positively associated with CRC in men adjusting for BMI, suggesting that TNF-α may influence colorectal carcinogenesis independent of adipocyte production.

摘要

目的

肥胖是结直肠癌(CRC)和腺瘤的已知危险因素。肥胖个体的循环中某些由脂肪细胞产生的内分泌和免疫因子浓度较高,这些因子部分解释了肥胖与结直肠肿瘤之间的关联。因此,我们评估了脂联素、瘦素和可溶性肿瘤坏死因子受体-2(sTNFR2)的血浆浓度与 CRC 和腺瘤的关系。

方法

我们确定了 193 例 CRC 病例和 193 例匹配对照,以及 131 例结直肠腺瘤病例和 131 例匹配对照,这些病例均嵌套在马里兰州华盛顿县 CLUE II 队列的内镜检查中。使用 ELISA 测量血浆标志物。分别对 CRC 和腺瘤的血浆标志物四分位距进行条件逻辑回归,以估计比值比(OR)和 95%置信区间(CI)。

结果

调整瘦素和脂联素后,sTNFR2 仅与男性 CRC 相关(Q4 与 Q1:OR=3.14,95%CI 1.11-8.86),在调整 BMI 后(3.46,95%CI 1.19-10.06)也保持不变。瘦素和脂联素与 CRC 总体风险或男性或女性无关。脂联素、瘦素和 sTNFR2 与腺瘤总体风险或男性或女性均无关。

结论

在这项研究中,瘦素和脂联素与结直肠癌变无关,因此似乎不是肥胖与结直肠癌变之间关联的基础。sTNFR2 是 TNF-α 的相关因子,在调整 BMI 后与男性 CRC 呈正相关,表明 TNF-α 可能独立于脂肪细胞产生影响结直肠癌变。

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