A Metabolomics Analysis of Body Mass Index and Postmenopausal Breast Cancer Risk
A Metabolomics Analysis of Body Mass Index and Postmenopausal Breast Cancer Risk
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DOI：
10.1093/jnci/djx244
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发表时间：
2018-06-01
影响因子：
10.3
通讯作者：
Ziegler, Regina G.
中科院分区：
文献类型：
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作者：
Moore, Steven C.;Playdon, Mary C.;Ziegler, Regina G.
背景：体重指数（BMI）升高与绝经后乳腺癌风险增加相关。潜在的机制，但是，仍然hailey.Methods：在巢式病例对照研究621绝经后乳腺癌病例参与者和621匹配的对照参与者，我们测量了617代谢物在诊断前血清。我们计算了代谢物和BMI之间的偏皮尔逊相关性，然后评估了BMI相关代谢物（617次统计检验的Bonferroni校正α水平= P < 8.10 x 10（-5））与浸润性乳腺癌的关系。比较第90百分位数与第10百分位数（在连续基础上建模），使用条件Logistic回归估计乳腺癌的比值比（OR），同时控制乳腺癌风险因素，包括BMI。具有最低P值的甲硫氨酸（错误发现率< 0.2）相互调整，以确定与乳腺癌风险独立相关的代谢物。结果：在67种BMI相关代谢物中，有两种与浸润性乳腺癌风险独立相关：16 α-羟基-DHEA-3-硫酸盐（OR = 1.65，95%置信区间[CI] = 1.22至2.22）和3-甲基戊二酰亚胺（OR = 1.67，95% CI = 1.21至2.30）。四种代谢物与雌激素受体阳性（ER i）乳腺癌风险独立相关：16-α-羟基-DHEA-3-硫酸盐（OR = 1.84，95% CI= 1.27 - 2.67），3-甲基戊二酰亚胺（OR = 1.91，95%CI = 1.23 ~ 2.96）、别异亮氨酸（OR = 1.76，95%CI =1.23 ~ 2.51）和2-甲基丁酰肉毒碱（OR =1.89，95%CI =1.22 ~ 2.91）。在没有代谢物的模型中，BMI每增加5 kg/m2，乳腺癌风险增加14（OR = 1.14，95%CI =1.01 - 1.28），但加入16 α-羟基-DHEA-3-硫酸盐和3-甲基戊二酰肉碱削弱了这种关联（OR = 1.06，95%CI = 0.93 ~ 1.20），logOR衰减57.6%（95% CI = 21.8%至100.0+%）。这四种代谢物可能是导致乳腺癌发生的代谢途径的信号，也是BMI与绝经后乳腺癌发病率增加相关性的基础。乳腺癌风险。这些发现值得进一步推广。
Background: Elevated body mass index (BMI) is associated with increased risk of postmenopausal breast cancer. The underlying mechanisms, however, remain elusive.Methods: In a nested case-control study of 621 postmenopausal breast cancer case participants and 621 matched control participants, we measured 617 metabolites in prediagnostic serum. We calculated partial Pearson correlations between metabolites and BMI, and then evaluated BMI-associated metabolites (Bonferroni-corrected alpha level for 617 statistical tests = P < 8.10 x 10(-5)) in relation to invasive breast cancer. Odds ratios (ORs) of breast cancer comparing the 90th vs 10th percentile (modeled on a continuous basis) were estimated using conditional logistic regression while controlling for breast cancer risk factors, including BMI. Metabolites with the lowest P values (false discovery rate < 0.2) were mutually adjusted for one another to determine those independently associated with breast cancer risk.Results: Of 67 BMI-associated metabolites, two were independently associated with invasive breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.65, 95% confidence interval [CI] = 1.22 to 2.22) and 3-methylglutarylcamitine (OR = 1.67, 95% CI = 1.21 to 2.30). Four metabolites were independently associated with estrogen receptor-positive (ER i) breast cancer risk: 16-ahydroxy-DHEA-3-sulfate (OR = 1.84, 95% CI= 1.27 to 2.67), 3-methylglutarylcamitine (OR = 1.91, 95% CI = 1.23 to 2.96), alloisoleucine (OR = 1.76, 95% CI =1.23 to 2.51), and 2-methylbutyrylcarnitine (OR =1.89, 95% CI =1.22 to 2.91). In a model without metabolites, each 5 kg/m(2) increase in BMI was associated with a 14% higher risk of breast cancer (OR = 1.14, 95% CI =1.01 to 1.28), but adding 16a-hydroxy-DHEA-3-sulfate and 3-methylglutarylcarnitine weakened this association (OR = 1.06, 95% CI = 0.93 to 1.20), with the logOR attenuating by 57.6% (95% CI = 21.8% to 100.0+%).Conclusion: These four metabolites may signal metabolic pathways that contribute to breast carcinogenesis and that underlie the association of BMI with increased postmenopausal breast cancer risk. These findings warrant further replication efforts.