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[背景]流行病学证据表明,阳光暴露与乳腺癌风险之间存在负性相关。假设其机制是阳光诱导皮肤合成维生素D。[目的]探讨阳光暴露及其与维生素D受体(VDR)基因变异的交互作用对乳腺癌风险的影响。[方法]在前瞻性农业健康研究队列的入组人群中,研究31 021位持有私人执照的杀虫剂从业人员的妻子受到的阳光暴露与乳腺癌发病率,其中包括578个病例,平均随访8.6年。在一项由293名病例和586名匹配对照组成的巢式病例-对照研究中,评估阳光暴露、VDR变异体与乳腺癌之间的交互作用。有关阳光暴露的信息来自于队列入组时的问卷调查。对队列数据采用Cox比例风险回归估计相对风险,对巢式病例-对照数据采用条件logistic回归估计相对风险。[结果]在所有参与者中,患乳腺癌风险的小幅度下降与随访前10年中平时阳光暴露≥1 h/d相关(与<1 h/d相比)[风险比(HR)=0.8;95%CI:0.6～1.0]。这一相关性在雌激素受体阳性肿瘤(HR=0.7;95%CI:0.5～0.9)中比雌激素受体阴性肿瘤(HR=1.1;95%CI:0.6～2.1)中稍强。阳光暴露≥1 h/d和一个VDR单倍型的联合HR低于预期,因为单一暴露的HR为负值(交互作用,P=0.07)。[结论]上述研究结果提示,阳光暴露可能与乳腺癌风险降低相关,但是研究中并没有发现通过VDR变异体修饰的明确证据。需要进行更大规模的研究,特别是平时阳光暴露水平低的人群中可能能够更精确描述。
[Background] Epidemiological evidence suggests that there is a negative correlation between sun exposure and breast cancer risk. Assuming that the mechanism is sunshine-induced skin synthesis of vitamin D [Objective] To investigate the effects of sun exposure and its interaction with vitamin D receptor (VDR) gene mutation on the risk of breast cancer. [Methods] Among the enrolled cohorts of the prospective agricultural health research cohort, the sunshine exposure and the incidence of breast cancer among 31,021 wizards of pesticide practitioners holding private licenses were investigated, including 578 cases with average follow-up 8.6 years. In a nested case-control study of 293 patients and 586 matched controls, sun exposure, VDR variants, and breast cancer were evaluated for interaction. The information on sun exposure comes from a questionnaire when cohorts are enrolled. Cox proportional hazards regression was used to estimate relative risk in the cohort data and conditional risk regression was used to estimate the relative risk in the nested case-control data. [Results] In all participants, the small decrease in risk of breast cancer was associated with ≥ 1 h / d of normal sun exposure during the first 10 years of follow-up (compared with <1 h / d) [hazard ratio (HR) = 0.8 ; 95% CI: 0.6 ~ 1.0]. This correlation was slightly stronger in estrogen receptor positive tumors (HR = 0.7; 95% CI: 0.5-0.9) than in estrogen receptor negative tumors (HR = 1.1; 95% CI: 0.6-2.1). The combined HR for sun exposure ≥1 h / d and one VDR haplotype was lower than expected because HR for a single exposure was negative (interaction, P = 0.07). [Conclusion] The above results suggest that the sun exposure may be related to the reduced risk of breast cancer. However, no clear evidence of modification by VDR variants was found in the study. More research is needed, especially in people with low levels of usual sun exposure.