Verheus Martijn, McKay James D, Kaaks Rudolf, Canzian Federico, Biessy Carine, Johansson Mattias, Grobbee Diederick E, Peeters Petra H M, van Gils Carla H
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands.
Breast Cancer Res Treat. 2008 Nov;112(1):109-22. doi: 10.1007/s10549-007-9827-x. Epub 2007 Dec 7.
High breast density is one of the strongest known risk factors for developing breast cancer. Insulin-like growth factor I (IGF-I) is a strong mitogen and has been suggested to increase breast cancer risk by increasing the amount of dense tissue in the female breast.
We wanted to investigate the effect of common variation in the IGF-1 gene on serum IGF-I levels and on breast density.
Mammograms and blood samples of 1,928 premenopausal participants of the Dutch Prospect-EPIC cohort were collected at baseline. Using a haplotype tagging approach, 16 single nucleotide polymorphisms (SNP) from three blocks covering the IGF-1 gene were genotyped in all study participants. Breast density was assessed using a quantitative computer-assisted method. For a subgroup of women, who went through menopause within 5 years after recruitment (n=656), premenopausal IGF-I levels and additionally postmenopausal breast density were determined. False positive report probabilities (FPRP) for statistically significant relations were calculated using the Wacholder method.
The minor alleles of five SNPs in block 3 were significantly associated with elevated levels of IGF-I (rs9989002, rs2033178, rs7136446, rs978458, rs6220; P-values: 0.01-0.04). The same SNPs were related with modestly higher percent breast density before menopause and-in the subgroup of women that became postmenopausal during follow-up-with a modestly higher percent breast density after menopause. The most significant result, i.e. the relation between rs6220 and IGF-I levels, had an FPRP<0.5 assuming prior probabilities of 0.01 and higher.
Common genetic variation in the IGF-1 gene is related to circulating levels of IGF-I, but the relationship with breast density is indecisive.
高乳腺密度是已知的患乳腺癌最强风险因素之一。胰岛素样生长因子I（IGF-I）是一种强大的促有丝分裂原，有人认为它通过增加女性乳腺致密组织的量来增加患乳腺癌风险。
我们想研究IGF-1基因常见变异对血清IGF-I水平和乳腺密度的影响。
在基线时收集了荷兰前瞻性-欧洲癌症与营养前瞻性调查（Prospect-EPIC）队列中1928名绝经前参与者的乳房X光片和血样。采用单倍型标签法，对所有研究参与者中覆盖IGF-1基因的三个区域的16个单核苷酸多态性（SNP）进行基因分型。使用定量计算机辅助方法评估乳腺密度。对于在招募后5年内绝经的一组女性（n = 656），测定绝经前IGF-I水平以及绝经后乳腺密度。使用瓦霍尔德方法计算具有统计学显著关系的假阳性报告概率（FPRP）。
区域3中五个SNP的次要等位基因与IGF-I水平升高显著相关（rs9989002、rs2033178、rs7136446、rs978458、rs6220；P值：0.01 - 0.04）。相同的SNP与绝经前略高的乳腺密度百分比相关，并且在随访期间绝经的女性亚组中，与绝经后略高的乳腺密度百分比相关。最显著的结果，即rs6220与IGF-I水平之间的关系，假设先验概率为0.01及更高时，FPRP < 0.5。
IGF-1基因的常见遗传变异与IGF-I的循环水平相关，但与乳腺密度的关系不明确。
