Department of Epidemiology and Biostatistics, Texas A&M School of Rural Public Health, College Station, TX 77843, USA.
Cancer Causes Control. 2013 Mar;24(3):587-94. doi: 10.1007/s10552-012-9997-7. Epub 2012 May 27.
There is increasing evidence that exposures in early life affect breast cancer risk, and that breast cancer etiology differs by tumor subtype. If environmental exposures in early life contribute to risk, it is expected that there would be clustering of women with breast cancer by their place of birth, and that clustering might differ by subtype. We examined spatial associations between place of birth and breast cancer by subtype, using hormone receptor status and molecular profiles of breast tumors.
Data were drawn from the Western New York Exposures and Breast Cancer study, a population-based case-control study of incident, pathologically confirmed breast cancer (1996-2001) in Erie and Niagara Counties. Included were women born in the study area (579 cases and 931 controls). Clustering of breast cancer subgroups relative to controls was examined by the k-function method in groups stratified by estrogen receptor (ER), progesterone receptor (PR), and HER2 status, and by DNA methylation status and p53 mutation status, and the k-function difference was used to compare relative spatial aggregation and spatial range of the difference between case subgroups and controls.
We found a tendency to cluster among ER positive, PR positive, and HER2 negative cases (i.e., luminal A subtype), especially among premenopausal women, but not among the other groups defined by hormonal receptor status, or by either methylation or p53 mutation status.
While our findings cannot rule out clustering of cases by birth place because of shared behaviors related to residence location, they also suggest that early life environmental exposures may affect subsequent breast cancer risk, and that premenopausal breast tumors of the luminal A subtype may be more affected by these early life exposures than other subtypes.
越来越多的证据表明，生命早期的暴露会影响乳腺癌的风险，并且乳腺癌的病因因肿瘤亚型而异。如果环境暴露在生命早期会增加风险，那么预计乳腺癌患者的出生地会存在聚集现象，并且这种聚集可能因亚型而异。我们使用激素受体状态和乳腺癌肿瘤的分子特征，检查了不同出生地区与乳腺癌亚型之间的空间关联。
数据来自于西部纽约暴露与乳腺癌研究，这是一项针对伊利县和尼亚加拉县（1996-2001 年）发病的、基于人群的乳腺癌病例对照研究。包括出生在研究区域的女性（579 例病例和 931 例对照）。使用 k 函数方法在雌激素受体（ER）、孕激素受体（PR）和 HER2 状态分层的组中，以及在 DNA 甲基化状态和 p53 突变状态分层的组中，检查乳腺癌亚组相对于对照组的聚类情况，并使用 k 函数差异来比较病例亚组与对照组之间相对空间聚集和差异的空间范围。
我们发现 ER 阳性、PR 阳性和 HER2 阴性病例（即 luminal A 亚型）之间存在聚集的趋势，尤其是在绝经前女性中，但在其他根据激素受体状态或甲基化或 p53 突变状态定义的组中则没有。
虽然我们的研究结果不能排除由于与居住地点相关的共同行为导致的病例出生地聚类，但它们也表明，生命早期的环境暴露可能会影响随后的乳腺癌风险，并且 luminal A 亚型的绝经前乳腺癌肿瘤可能比其他亚型更容易受到这些早期生活暴露的影响。
