Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
Department of Epidemiology, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands.
Eur J Nutr. 2019 Apr;58(3):1033-1045. doi: 10.1007/s00394-018-1619-z. Epub 2018 Feb 14.
The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology.
The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n = 1449) and ER+ breast cancer cases (n = 844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3 years of follow-up.
Unexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+ breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+ breast cancer risk.
This study did not provide evidence for a positive association between acrylamide intake and ER+ breast cancer risk. If anything, acrylamide was associated with a decreased ER+ breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+ breast cancer risk through sex hormone pathways.
在流行病学研究中，饮食丙烯酰胺摄入与雌激素受体阳性（ER+）乳腺癌风险之间的关联并不一致。通过分析 ER+乳腺癌风险的基因-丙烯酰胺相互作用，我们旨在阐明丙烯酰胺摄入在 ER+乳腺癌发病机制中的作用。
前瞻性荷兰饮食与癌症队列研究纳入了 62573 名年龄在 55-69 岁的女性。在基线时，从总队列中随机抽取 2589 名女性组成子队列，采用病例-子队列分析方法。通过食物频率问卷评估子队列成员（n=1449）和 ER+乳腺癌病例（n=844）的饮食丙烯酰胺摄入量。我们对丙烯酰胺代谢、性激素系统、氧化应激和 DNA 修复相关基因中的单核苷酸多态性（SNP）进行了基因分型。基于 20.3 年的随访，采用 Cox 比例风险分析评估丙烯酰胺摄入量与 SNPs 之间的相乘性交互作用。
出乎意料的是，在所有女性中，丙烯酰胺与 ER+乳腺癌风险之间呈统计学上无显著负相关，但没有明确的剂量反应关系，且在从不吸烟者中无相关性。在 57 个 SNP 和 2 个基因缺失的结果中，CYP1B1 中的 rs1056827、CYP11A1 中的 rs2959008 和 rs7173655、GSTT1 基因缺失和 hOGG1 中的 rs1052133 与 ER+乳腺癌风险与丙烯酰胺摄入之间存在统计学显著的交互作用。
本研究并未提供丙烯酰胺摄入与 ER+乳腺癌风险之间存在正相关的证据。如果有的话，丙烯酰胺与 ER+乳腺癌风险降低相关。与 CYP1B1 和 CYP11A1 中的 SNP 的相互作用表明，丙烯酰胺可能通过性激素途径影响 ER+乳腺癌风险。
