Schernhammer Eva S, Berrino Franco, Krogh Vittorio, Secreto Giorgio, Micheli Andrea, Venturelli Elisabetta, Sieri Sabina, Sempos Christopher T, Cavalleri Adalberto, Schünemann Holger J, Strano Sabrina, Muti Paola
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA.
J Natl Cancer Inst. 2008 Jun 18;100(12):898-905. doi: 10.1093/jnci/djn171. Epub 2008 Jun 10.
Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women. However, the association between melatonin levels and breast cancer risk in postmenopausal women remains unclear.
We investigated the association between melatonin levels and breast cancer risk in postmenopausal women in a prospective case-control study nested in the Hormones and Diet in the Etiology of Breast Cancer Risk cohort, which included 3966 eligible postmenopausal women. The concentration of melatonin's major metabolite, 6-sulfatoxymelatonin, was measured in a baseline 12-hour overnight urine sample from 178 women who later developed incident breast cancer and from 710 matched control subjects. We used multivariable-adjusted conditional logistic regression models to investigate associations. Relative risks are reported as odds ratios (ORs). All statistical tests were two-sided.
Increased melatonin levels were associated with a statistically significantly lower risk of invasive breast cancer in postmenopausal women (for women in the highest quartile of total overnight 6-sulfatoxymelatonin output vs the lowest quartile, multivariable OR also adjusted for testosterone = 0.56, 95% confidence interval [CI] = 0.33 to 0.97; P(trend) = .02). This association was strongest among never and past smokers (OR = 0.38, 95% CI = 0.20 to 0.74; P(trend) = .001) and after excluding women who were diagnosed with invasive breast cancer within 4 years after urine collection (OR = 0.34, 95% CI = 0.15 to 0.75; P(trend) = .002). We did not observe substantial variation in relative risks by hormone receptor status of breast tumors. Among the 3966 women in the cohort, 40 of the 992 women in the highest quartile of 6-sulfatoxymelatonin developed breast cancer during follow-up, compared with 56 of the 992 women in the lowest quartile of 6-sulfatoxymelatonin.
Results from this prospective study provide evidence for a statistically significant inverse association between melatonin levels, as measured in overnight morning urine, and invasive breast cancer risk in postmenopausal women.
尿褪黑素水平低与绝经前女性患乳腺癌风险增加有关。然而，绝经后女性褪黑素水平与乳腺癌风险之间的关联仍不明确。
在“乳腺癌风险队列中激素与饮食”研究的前瞻性病例对照研究中，我们调查了绝经后女性褪黑素水平与乳腺癌风险之间的关联，该队列包括3966名符合条件的绝经后女性。在178名后来发生乳腺癌的女性和710名匹配的对照者的基线12小时夜间尿液样本中，测量了褪黑素主要代谢产物6-硫酸氧褪黑素的浓度。我们使用多变量调整的条件逻辑回归模型来研究关联。相对风险以比值比（OR）表示。所有统计检验均为双侧检验。
绝经后女性中，褪黑素水平升高与浸润性乳腺癌风险在统计学上显著降低相关（总夜间6-硫酸氧褪黑素排出量最高四分位数的女性与最低四分位数的女性相比，多变量OR在调整睾酮后=0.56，95%置信区间[CI]=0.33至0.97；P（趋势）=.02）。这种关联在从不吸烟者和既往吸烟者中最强（OR=0.38，95%CI=0.20至0.74；P（趋势）=.001），在排除尿液采集后4年内被诊断为浸润性乳腺癌的女性后（OR=0.34，95%CI=0.15至0.75；P（趋势）=.002）。我们未观察到乳腺癌激素受体状态导致的相对风险有实质性差异。在该队列的3966名女性中，6-硫酸氧褪黑素最高四分位数的992名女性中有40名在随访期间患乳腺癌，而6-硫酸氧褪黑素最低四分位数的992名女性中有56名患乳腺癌。
这项前瞻性研究的结果为夜间晨尿中测量的褪黑素水平与绝经后女性浸润性乳腺癌风险之间存在统计学显著负相关提供了证据。
