Lukanova Annekatrin, Toniolo Paolo, Zeleniuch-Jacquotte Anne, Grankvist Kjell, Wulff Marianne, Arslan Alan A, Afanasyeva Yelena, Johansson Robert, Lenner Per, Hallmans Göran, Wadell Göran, Lundin Eva
Division of Epidemiology, Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, NBV 9E2, New York, NY 10016, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2489-93. doi: 10.1158/1055-9965.EPI-06-0625. Epub 2006 Nov 28.
The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy.
The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).
Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II.
The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy.
尽管有大量关于胰岛素样生长因子(IGF)-I与乳腺癌或高危乳腺钼靶密度相关性的报道,但IGF-I在乳腺癌中的作用仍存在争议。我们推测,在妊娠早期暴露于升高的IGF-I,这一时期乳房中细胞增殖活跃且存在高浓度性类固醇,将增加母亲患乳腺恶性肿瘤的风险。
瑞典北部产妇队列研究是一项正在进行的前瞻性研究,自1975年起收集孕早期妇女的血液样本作为传染病筛查的一部分。一项病例对照研究(212例病例和369例对照)嵌套于瑞典北部产妇队列中分娩单胎婴儿的成员。采用放射免疫分析法测量IGF-I和IGF-II水平。使用条件逻辑回归来估计比值比(OR)和95%置信区间(95%CI)。
乳腺癌风险随IGF-I水平升高而增加(最高三分位数OR为1.7;95%CI为1.1 - 2.7)。初产妇中的关联更强(OR为2.2;95%CI为1.1 - 4.4),而非初产妇中为(OR为1.4;95%CI为0.7 - 2.8)。在采样时年龄<28岁、28至33岁和>33岁的组中,最高三分位数风险似乎有所降低,分别从2.5(0.9 - 7.6)降至2.1(0.9 - 5.0)和1.2(0.5 - 2.5)。乳腺癌与孕早期IGF-II无关联。
该研究提供了进一步证据表明IGF-I在乳腺癌中很重要。我们的研究结果表明,IGF-I对乳房的不良影响在首次妊娠引起的腺体重塑之前可能更强。