Lambe M, Thörn M, Sparén P, Bergström R, Adami H O
Department of Social Medicine, University Hospital, Uppsala, Sweden.
Melanoma Res. 1996 Apr;6(2):147-53.
Pigmentary changes during pregnancy and sex-specific differences in incidence patterns of cutaneous malignant melanoma (CMM) suggest that sex hormones may be involved in the development of CMM. We explored possible associations between childbearing and the risk of CMM in a case-control study "nested' in a nation-wide cohort. A total of 4,779 incident cases of CMM in women aged 24-65 were compared with 23,888 individually age-matched controls. Delayed childbearing was associated with an increased risk of CMM, corresponding to approximately 16% per 5 years. Parous women had a significantly lower risk of CMM compared with nulliparous women; in univariate analysis there was an 8% reduction in risk for each additional birth (odds ratio = 0.92; 95% confidence interval = 0.89-0.95). In multivariate analyses the risk of CMM was best explained by a model including both age at first birth and parity. Age at first birth was the most important variable. Time since most recent birth was unrelated to risk of CMM. These findings indicate that early childbearing and multiparity reduce the risk of CMM. Conceivable explanations are hormonal changes induced by childbearing, enhanced immunologic activity via exposure to fetal antigens during pregnancy, or long-lasting effects of pregnancy-associated hyperpigmentation. Our results need confirmation in studies with proper adjustment for confounding; less sun exposure in young mothers and high parity women may represent an alternative explanation but is unlikely to explain entirely the twofold difference in risk found between extreme categories of age at first birth and parity.
孕期色素沉着变化以及皮肤恶性黑色素瘤（CMM）发病模式的性别差异表明，性激素可能参与了CMM的发生发展。我们在一项全国性队列中“嵌套”的病例对照研究中，探讨了生育与CMM风险之间可能存在的关联。将24至65岁女性中4779例CMM新发病例与23888例个体年龄匹配的对照进行比较。晚育与CMM风险增加相关，每5年约增加16%。经产妇患CMM的风险显著低于未产妇；单因素分析中，每增加一次生育风险降低8%（比值比=0.92；95%置信区间=0.89-0.95）。多因素分析中，CMM风险最好由一个包括初产年龄和产次的模型来解释。初产年龄是最重要的变量。距最近一次生育的时间与CMM风险无关。这些发现表明，早育和多产可降低CMM风险。可能的解释是生育引起的激素变化、孕期接触胎儿抗原导致的免疫活性增强，或与妊娠相关的色素沉着的长期影响。我们的结果需要在对混杂因素进行适当调整的研究中得到证实；年轻母亲和多产妇女日照较少可能是另一种解释，但不太可能完全解释初产年龄和产次极端类别之间发现的两倍风险差异。
