Adiposity and cancer: a Mendelian randomization analysis in the UK biobank
Adiposity and cancer: a Mendelian randomization analysis in the UK biobank
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DOI：
10.1038/s41366-021-00942-y
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发表时间：
2021-08-27
影响因子：
4.9
通讯作者：
Hypponen, Elina
中科院分区：
文献类型：
--
作者：
Ahmed, Muktar;Mulugeta, Anwar;Hypponen, Elina
背景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，但尚不清楚这些是否取决于相关的代谢异常。方法 我们使用了英国生物银行 321,472 名参与者的信息，其中包括 30,561 例与肥胖相关的癌症。我们构建了三种反映较高肥胖程度的遗传工具以及“不利”（82 个 SNP）、“有利”（24 个 SNP）或“中性”代谢特征（25 个 SNP）。我们研究了与 14 种癌症的关联，之前认为这些癌症与肥胖有关。结果 所有遗传仪器均与 BMI 具有很强的相关性（全部 p < 1 x 10(-300)）。反映不利的肥胖的仪器还与较高的 CRP、HbA1c 和不良的血脂状况相关，而反映代谢有利的肥胖的仪器与较低的 HbA1c 和良好的血脂状况相关。在 MR 逆方差加权分析中，不利的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较低相关（OR = 0.80，95% CI：0.72，0.89）。对于个别癌症，MR 分析表明，更多的基因检测不良肥胖会导致多发性骨髓瘤（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较低（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个体癌症的几率无关。结论 肥胖程度较高与非激素癌症的风险较高相关，但与某些激素相关癌症的风险较低相关。代谢异常的存在可能会加剧肥胖对癌症的不利影响。需要进一步的研究来调查对不良代谢健康的干预是否有助于减轻与肥胖相关的癌症风险。
Background Observational and Mendelian randomization (MR) studies link obesity and cancer, but it remains unclear whether these depend upon related metabolic abnormalities. Methods 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. Results All genetic instruments had a strong association with BMI (p < 1 x 10(-300) 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. Conclusions 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.