Helzlsouer K J, Alberg A J, Norkus E P, Morris J S, Hoffman S C, Comstock G W
Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA.
J Natl Cancer Inst. 1996 Jan 3;88(1):32-7. doi: 10.1093/jnci/88.1.32.
Antioxidant micronutrients, such as alpha-tocopherol (vitamin E), the carotenoids, and selenium, may protect against the development of cancer by preventing free radical damage at the cellular level.
A nested case--control study was conducted among donors to a serum bank to examine the association between levels of serum micronutrients and/or cholesterol and the development of ovarian cancer.
In 1974, sera were collected from 20,305 residents of Washington County, MD, over a 4-month period and stored at -70 degrees C. Serum micronutrient concentrations of women who developed ovarian cancer (case subjects, n = 35) were compared with those of women who remained free of cancer and who were matched to case subjects on age and menopausal status (control subjects, n = 67). Serum levels of retinol (vitamin A), alpha- and beta-carotene (the major provitamin A), lycopene (a carotenoid), and alpha- and gamma-tocopherol were measured using high-performance liquid chromatography. Serum selenium was measured by neutron activation analysis. Cholesterol was measured by enzymatic assay. The data were categorized into thirds and conditional logistic regression analyses were performed to determine the association between prediagnostic serum cholesterol and micronutrient levels and the development of ovarian cancer; matched odds ratios (ORs) were determined from these regression analyses. P values for trend and for interaction were calculated with the use of two-sided likelihood ratio tests.
Higher serum alpha-tocopherol levels were associated with an increased risk of ovarian cancer (P for trend = .04); however, this association diminished after adjustment for cholesterol. Women with higher serum cholesterol levels had an increased risk of ovarian cancer compared with women in the lowest third of cholesterol levels (OR = 3.2; 95% confidence interval = 0.9-11.3). The association between serum cholesterol levels and the risk of ovarian cancer was examined, stratifying by micronutrient level. The general pattern observed was an increased risk of ovarian cancer associated with cholesterol levels greater than 200 mg/dL, regardless of the micronutrient level. Serum selenium was associated with a decreased risk of ovarian cancer only among case participants diagnosed 4 or more years after blood collections (P for trend = .02). Concentrations of carotenoids and retinol were not associated with the development of ovarian cancer.
Selenium may have a protective role against the development of ovarian cancer. Higher serum cholesterol levels were associated with an increased risk of developing ovarian cancer; an association that persisted regardless of serum micronutrient level.
Given the small size of this study and the inconsistency of results among the few prospective studies of ovarian cancer conducted to test these associations, replications of these findings are highly desirable.
抗氧化微量营养素，如α-生育酚（维生素E）、类胡萝卜素和硒，可能通过防止细胞水平的自由基损伤来预防癌症的发生。
在一家血清库的捐赠者中进行了一项巢式病例对照研究，以检查血清微量营养素水平和/或胆固醇水平与卵巢癌发生之间的关联。
1974年，在4个月的时间里从马里兰州华盛顿县的20305名居民中采集血清，并储存在-70℃。将患卵巢癌的女性（病例组，n = 35）的血清微量营养素浓度与未患癌症且在年龄和绝经状态上与病例组匹配的女性（对照组，n = 67）的血清微量营养素浓度进行比较。使用高效液相色谱法测量血清视黄醇（维生素A）、α-和β-胡萝卜素（主要维生素A原）、番茄红素（一种类胡萝卜素）以及α-和γ-生育酚的水平。通过中子活化分析测量血清硒。通过酶法测定胆固醇。数据被分为三等份，并进行条件逻辑回归分析以确定诊断前血清胆固醇和微量营养素水平与卵巢癌发生之间的关联；从这些回归分析中确定匹配优势比（OR）。使用双侧似然比检验计算趋势和交互作用的P值。
血清α-生育酚水平较高与卵巢癌风险增加相关（趋势P值 = 0.04）；然而，在调整胆固醇后这种关联减弱。与胆固醇水平处于最低三分之一的女性相比，血清胆固醇水平较高的女性患卵巢癌的风险增加（OR = 3.2；95%置信区间 = 0.9 - 11.3）。按微量营养素水平分层，检查血清胆固醇水平与卵巢癌风险之间的关联。观察到的总体模式是，无论微量营养素水平如何，胆固醇水平高于200mg/dL与卵巢癌风险增加相关。仅在采血后4年或更长时间被诊断的病例参与者中，血清硒与卵巢癌风险降低相关（趋势P值 = 0.02）。类胡萝卜素和视黄醇的浓度与卵巢癌的发生无关。
硒可能对卵巢癌的发生具有保护作用。血清胆固醇水平较高与患卵巢癌的风险增加相关；无论血清微量营养素水平如何，这种关联都持续存在。
鉴于本研究规模较小，且在为检验这些关联而进行的少数卵巢癌前瞻性研究中结果不一致，非常需要对这些发现进行重复研究。
