Australian Centre for Precision Health, Unit of Clinical and Health Sciences and Unit of Allied Health and Human Performance, University of South Australia, Adelaide, SA, Australia.
Department of Epidemiology, Faculty of Public Health, Jimma University Institute of Health, Jimma, Ethiopia.
Int J Obes (Lond). 2021 Dec;45(12):2657-2665. doi: 10.1038/s41366-021-00942-y. Epub 2021 Aug 27.
Observational and Mendelian randomization (MR) studies link obesity and cancer, but it remains unclear whether these depend upon related metabolic abnormalities.
We used information from 321,472 participants in the UK biobank, including 30,561 cases of obesity-related cancer. We constructed three genetic instruments reflecting higher adiposity together with either "unfavourable" (82 SNPs), "favourable" (24 SNPs) or "neutral" metabolic profile (25 SNPs). We looked at associations with 14 types of cancer, previously suggested to be associated with obesity.
All genetic instruments had a strong association with BMI (p < 1 × 10 for all). The instrument reflecting unfavourable adiposity was also associated with higher CRP, HbA1c and adverse lipid profile, while instrument reflecting metabolically favourable adiposity was associated with lower HbA1c and a favourable lipid profile. In MR-inverse-variance weighted analysis unfavourable adiposity was associated with an increased risk of non-hormonal cancers (OR = 1.22, 95% confidence interval [CI]:1.08, 1.38), but a lower risk of hormonal cancers (OR = 0.80, 95%CI: 0.72, 0.89). From individual cancers, MR analyses suggested causal increases in the risk of multiple myeloma (OR = 1.36, 95%CI: 1.09, 1.70) and endometrial cancer (OR = 1.77, 95%CI: 1.16, 2.68) by greater genetically instrumented unfavourable adiposity but lower risks of breast and prostate cancer (OR = 0.72, 95%CI: 0.61, 0.83 and OR = 0.81, 95%CI: 0.68, 0.97, respectively). Favourable or neutral adiposity were not associated with the odds of any individual cancer.
Higher adiposity associated with a higher risk of non-hormonal cancer but a lower risk of some hormone related cancers. Presence of metabolic abnormalities might aggravate the adverse effects of higher adiposity on cancer. Further studies are warranted to investigate whether interventions on adverse metabolic health may help to alleviate obesity-related cancer risk.
观察性研究和孟德尔随机化（MR）研究将肥胖与癌症联系起来，但目前尚不清楚这些是否取决于相关的代谢异常。
我们使用了英国生物库 321472 名参与者的信息，包括 30561 例与肥胖相关的癌症病例。我们构建了三个反映更高体脂的遗传工具，这些工具与“不利”（82 个 SNP）、“有利”（24 个 SNP）或“中性”代谢特征（25 个 SNP）相关联。我们观察了与 14 种先前被认为与肥胖有关的癌症之间的关联。
所有遗传工具与 BMI 均具有很强的关联（所有工具的 p 值均小于 1×10）。反映不利肥胖的工具也与 CRP、HbA1c 和不良血脂谱升高相关，而反映代谢有利肥胖的工具与 HbA1c 降低和有利血脂谱相关。在 MR 逆方差加权分析中，不利肥胖与非激素癌症的风险增加相关（OR=1.22，95%置信区间 [CI]：1.08，1.38），但与激素癌症的风险降低相关（OR=0.80，95%CI：0.72，0.89）。从个别癌症来看，MR 分析表明，通过更大的遗传工具衡量的不利肥胖，多发性骨髓瘤（OR=1.36，95%CI：1.09，1.70）和子宫内膜癌（OR=1.77，95%CI：1.16，2.68）的风险增加，但乳腺癌和前列腺癌的风险降低（OR=0.72，95%CI：0.61，0.83 和 OR=0.81，95%CI：0.68，0.97）。有利或中性肥胖与任何一种癌症的几率都没有关系。
更高的肥胖程度与非激素癌症的风险增加相关，但与某些激素相关癌症的风险降低相关。代谢异常的存在可能会加剧更高肥胖程度对癌症的不利影响。有必要进行进一步的研究，以探讨干预不良代谢健康是否有助于减轻肥胖相关癌症的风险。
