抗氧化维生素和 NOS3 基因多态性联合作用对女性乳腺癌风险的影响。

Combined effects of antioxidant vitamin and NOS3 genetic polymorphisms on breast cancer risk in women.

机构信息

Department of Preventive Medicine, Kangwon National University, Kangwon-do, Republic of Korea.

出版信息

Clin Nutr. 2012 Feb;31(1):93-8. doi: 10.1016/j.clnu.2011.08.005. Epub 2011 Aug 27.

DOI:10.1016/j.clnu.2011.08.005

Abstract

BACKGROUND & AIMS: It is becoming increasingly clear that there is wide heterogeneity in genetic predisposition to breast cancer and that breast cancer risk is determined by interactive effect between genetic and environmental factors.

METHODS

We investigated the combined effects of antioxidant vitamin intake and NOS3 genetic polymorphisms on breast cancer risk in a Korean population (Seoul Breast Cancer Study). Histologically confirmed breast cancer cases (n = 512) and age, menopause status-matched controls (n = 512) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 2001-2003. Two genetic polymorphisms of NOS3 (298G > T and -786 T > C) were assessed by single base extension assays.

RESULTS

No overall association between the individual NOS3 genotypes or diplotypes and breast cancer risk was found, although the difference between cases and controls in the frequency of the NOS3 894 G > T polymorphism showed borderline significance (OR = 0.74, 95% CI = 0.52-1.06). There was no significant difference in energy intake or the intake of antioxidant vitamins between cases and controls, with the exception of vitamin E (OR = 0.49 lowest vs. highest quartile, P(trend) < 0.01). On the other hand, our results suggest that antioxidant vitamin intake may modify the effects of the NOS3 -786 T > C or 894 G > T genetic polymorphisms on breast cancer risk. Although a multiplicative interaction was not observed, the protective effect of β-carotene intake on breast cancer risk was observed predominantly in individuals with the TG:TG diplotype of NOS3 (OR = 0.68) but not observed with others diplotype. An inverse association between vitamin E intake and breast cancer risk was observed for individuals with the NOS3 786 TC + TT genotype and the NOS3 894 GG genotype. In addition, folic acid had a protective effect in the NOS3 786 TT and NOS3 894 GT + TT genotype.

CONCLUSION

Our results suggest that intake of antioxidant vitamins might modify the association between genetic polymorphisms of NOS3 and breast cancer risk.

摘要

背景与目的

越来越明显的是，乳腺癌的遗传易感性存在广泛的异质性，并且乳腺癌风险是由遗传和环境因素的相互作用决定的。

方法

我们在韩国人群（首尔乳腺癌研究）中研究了抗氧化维生素摄入和 NOS3 基因多态性对乳腺癌风险的联合作用。我们招募了 2001 年至 2003 年期间来自首尔几家教学医院的组织学确诊的乳腺癌病例（n=512）和年龄、绝经状态匹配的对照（n=512），这些对照均无当前或既往癌症史。通过单碱基延伸分析评估了 NOS3 的两个基因多态性（298G>T 和-786T>C）。

结果

NOS3 个体基因型或单体型与乳腺癌风险之间没有总体关联，但病例与对照之间 NOS3 894 G>T 多态性的频率差异具有边缘显著性（OR=0.74，95%CI=0.52-1.06）。病例与对照之间的能量摄入或抗氧化维生素摄入没有显著差异，除了维生素 E（OR=0.49，最低与最高四分位数，P（趋势）<0.01）。另一方面，我们的结果表明，抗氧化维生素摄入可能会改变 NOS3-786T>C 或 894G>T 基因多态性对乳腺癌风险的影响。虽然没有观察到相乘交互作用，但β-胡萝卜素摄入对乳腺癌风险的保护作用主要在 NOS3 TG:TG 单体型个体中观察到（OR=0.68），而在其他单体型中未观察到。维生素 E 摄入与乳腺癌风险呈负相关，见于 NOS3 786 TC+TT 基因型和 NOS3 894 GG 基因型个体。此外，叶酸对 NOS3 786 TT 和 NOS3 894 GT+TT 基因型有保护作用。