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血浆中溴化阻燃剂浓度与绝经后乳腺癌风险:法国 E3N 队列的巢式病例对照研究。

Plasma concentration of brominated flame retardants and postmenopausal breast cancer risk: a nested case-control study in the French E3N cohort.

机构信息

CESP, Faculté de médecine, Université Paris-Saclay, UVSQ, INSERM, Villejuif, France.

Gustave Roussy, Villejuif, France.

出版信息

Environ Health. 2020 May 20;19(1):54. doi: 10.1186/s12940-020-00607-9.

Abstract

BACKGROUND

Brominated flame retardants (BFRs) are lipophilic substances with endocrine-disrupting properties. To date, only few investigations, mainly retrospective case-control studies, have explored the link between internal levels of BFRs and the risk of breast cancer, leading to conflicting results. We investigated the associations between plasma concentrations of two main groups of BFRs, PBDEs (pentabromodiphenyl ethers) and PBBs (polybrominated biphenyls), and the risk of breast cancer in a nested case-control study.

METHODS

A total of 197 incident breast cancer cases and 197 controls with a blood sample collected in 1994-1999 were included. Plasma levels of PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE153, BDE-154) and of PBB-153 were measured by gas chromatography coupled to high-resolution mass spectrometry. Conditional logistic regression models, adjusted for potential confounders, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS

Women were aged 56 years on average at blood draw. All cases, except for one, were diagnosed after menopause, with an average age at diagnosis of 68 years. Overall, we found no evidence of an association between plasma levels of PBDEs and PBB-153 and postmenopausal breast cancer risk (log-concentrations of BFRs yielding non-statistically significant ORs of 0.87 to 1.07). The analysis showed a non-linear inverse association for BDE-100 and BDE-153 and postmenopausal breast cancer risk; nevertheless, these findings were statistically significant only when the exposure was modeled as ng/L plasma (third vs. first quintile: OR = 0.42, 95%CI = 0.19-0.93 and OR = 0.42, 95%CI = 0.18-0.98, respectively) and not when modeled as ng/gr of lipids (OR = 0.58, 95%CI = 0.27-1.25 and OR = 0.53, 95%CI = 0.25-1.17). These results were unchanged in stratified analyses by tumor hormone receptor expression or body mass index.

CONCLUSIONS

Our results suggest no clear association between internal levels of PBDEs and PBB-153 and the risk of breast cancer in postmenopausal women. However, these findings need to be carefully interpreted, taking into account limitations due to the limited number of women included in the study, the lack of information concerning genetic susceptibility of cases, and the unavailability of exposure assessment during critical windows of susceptibility for breast cancer. More studies are warranted to further investigate the relationships between PBDE and PBB exposure and breast cancer risk.

摘要

背景

溴化阻燃剂 (BFRs) 是具有内分泌干扰特性的亲脂性物质。迄今为止,仅有少数几项主要为回顾性病例对照研究的调查探索了 BFR 体内水平与乳腺癌风险之间的联系,导致结果相互矛盾。我们在一项巢式病例对照研究中调查了两组主要 BFR(多溴二苯醚 (PBDEs) 和多溴联苯 (PBBs))的血浆浓度与乳腺癌风险之间的关联。

方法

共纳入 197 例新发病例和 197 例在 1994-1999 年采集血样的对照。通过气相色谱-高分辨率质谱联用仪测量 PBDE 同系物(BDE-28、BDE-47、BDE-99、BDE-100、BDE153、BDE-154)和 PBB-153 的血浆水平。使用条件逻辑回归模型,调整了潜在混杂因素,以估计比值比 (OR) 和 95%置信区间 (CI)。

结果

女性在采血时的平均年龄为 56 岁。除了 1 例以外,所有病例均在绝经后被诊断为乳腺癌,平均诊断年龄为 68 岁。总体而言,我们没有发现 PBDEs 和 PBB-153 血浆水平与绝经后乳腺癌风险之间存在关联(BFR 浓度的对数与非统计学显著的 OR 为 0.87 至 1.07)。分析显示,BDE-100 和 BDE-153 与绝经后乳腺癌风险呈非线性反比关系;然而,当将暴露量建模为血浆 ng/L(第三 vs. 第一五分位数:OR=0.42,95%CI=0.19-0.93 和 OR=0.42,95%CI=0.18-0.98)而不是以 ng/g 脂质建模时,这些发现才有统计学意义(OR=0.58,95%CI=0.27-1.25 和 OR=0.53,95%CI=0.25-1.17)。按肿瘤激素受体表达或体重指数进行分层分析后,结果保持不变。

结论

我们的结果表明,PBDEs 和 PBB-153 的体内水平与绝经后妇女的乳腺癌风险之间没有明确的关联。然而,这些发现需要谨慎解释,要考虑到由于研究中纳入的女性数量有限、缺乏有关病例遗传易感性的信息以及缺乏乳腺癌易感性关键窗口期的暴露评估,因此存在一定的局限性。需要进一步开展更多的研究,以进一步调查 PBDE 和 PBB 暴露与乳腺癌风险之间的关系。

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