The aetiology and pathogenesis of human breast cancer
The aetiology and pathogenesis of human breast cancer
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DOI：
10.1016/0027-5107(95)00128-x
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发表时间：
1995-12-01
影响因子：
2.3
通讯作者：
Trichopoulos, D
中科院分区：
文献类型：
--
作者：
Adami, HO;Persson, I;Trichopoulos, D
虽然研究人员已经清楚地表明，非遗传因素主导了人类乳腺癌的病因学，但他们未能从数量上确定重要的原因，预防的前景确实有限。然而，在过去几年中，流行病学和基础研究取得了进展。目前的证据表明，乳腺癌可能会受到子宫内环境的影响，青春期的暴露尤为重要，怀孕对乳腺癌风险有双重影响：早期增加，然后进行长期保护。在新生儿时期，乳腺导管系统的结构发育存在很大的差异--通过在宫内的推断--怀孕会导致乳腺结构的永久性变化。我们认为，这些观察结果符合病因学模型，包括以下关键组成部分：(1)乳腺癌风险取决于处于危险中的细胞的数量，单个细胞对恶性转化的敏感性，以及细胞增殖的程度，特别是可以作为乳腺癌创始人的细胞；(2)靶细胞的数量主要由生命早期的激素环境决定，可能已经在子宫中；(3)在成年生活中，非遗传毒性的激素通过增加选择性细胞增殖从而增加靶细胞的数量和保留自发的体细胞突变的风险来增加乳腺癌的风险；(4)虽然怀孕刺激了已经恶性的细胞或接近恶变的细胞的生长(从而导致短期的风险增加)，但由于永久性的结构变化、终末分化以及可能减少的细胞增殖和致癌物结合，出现了主要的长期保护。
Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn - and by inference in utero - and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination.