Kvaskoff Marina, Bijon Anne, Mesrine Sylvie, Vilier Alice, Baglietto Laura, Fournier Agnès, Clavel-Chapelon Françoise, Dossus Laure, Boutron-Ruault Marie-Christine
"Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Cancer Control Group, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
"Nutrition, Hormones and Women's Health" Team, Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), F-94805, Villejuif, France; Université Paris Sud 11, UMRS 1018, F-94807, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France.
PLoS Med. 2014 Jun 10;11(6):e1001660. doi: 10.1371/journal.pmed.1001660. eCollection 2014 Jun.
While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk.
We prospectively analyzed data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with "very many" nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674-4,649) per 100,000 women with "very many" nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose-response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD.
Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.
虽然黑素细胞痣与遗传因素及儿童期阳光暴露有关，但一些观察结果也表明激素对痣可能有影响。为了验证痣与乳腺肿瘤风险相关的假设，我们探讨了痣的数量与良性及恶性乳腺疾病风险之间的关系。
我们对E3N队列的数据进行了前瞻性分析，该队列由1990年纳入研究时年龄在40 - 65岁的法国女性组成。在纳入研究时收集了痣的数量。使用Cox比例风险回归模型计算乳腺癌的风险比（HRs）及95%置信区间（CIs）。使用逻辑回归估计痣的数量与良性乳腺疾病（BBD）个人史及乳腺癌家族史之间的关联。在1990年6月15日至2008年6月15日期间，在89,902名女性中确诊了5,956例新发乳腺癌病例（包括5,245例浸润性肿瘤）。在根据年龄、教育程度及已知乳腺癌风险因素进行调整的模型中，痣“非常多”的女性患乳腺癌的风险显著更高（HR = 1.13，95% CI = 1.01 - 1.27，与“无痣”者相比；趋势P值 = 0.04），不过在根据BBD个人史或乳腺癌家族史进行调整后，该显著性消失。浸润性乳腺癌的10年绝对风险从每100,000名无痣女性中的3,749例增加到每100,000名痣“非常多”的女性中的4,124例（95% CI = 3,674 - 4,649）。这种关联仅限于绝经前女性（HR = 1.40，趋势P值 = 0.01），即使在完全调整后（HR = 1.34，趋势P值 = 0.03；齐性P值 = 0.04）也是如此，但根据乳腺癌类型或激素受体状态并无差异。此外，我们观察到痣的数量与活检确诊的BBD病史（n = 5,169；趋势P值<0.0001）及一级亲属乳腺癌家族史（n = 7,472；趋势P值 = 0.0003）之间存在显著的剂量反应关系。我们研究的主要局限性包括使用定性量表自我报告痣的数量，以及自我报告的活检确诊BBD病史。
我们的研究结果表明痣的数量与绝经前乳腺癌风险、BBD及乳腺癌家族史之间存在关联。有必要进行更多研究以阐明这些关系并了解其潜在机制。
