Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

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A 57‐year‐old woman was investigated for obstructive jaundice with endoscopic retrograde cholangiopancreaticography that showed a tumor at the ampulla of Vater. A Whipple's procedure was performed. A protuberant tumor was present at the ampulla of Vater in the background of multiple mucosal polyps in the duodenum. Light microscopy revealed a diffuse non‐Hodgkin's lymphoma with centrocytelike cells forming lymphoepithelial lesions and infiltrating the sphincter of Oddi. The duodenal polyps were hyperplastic lymphoid follicles with reactive germinal centers. Immunohistochemical staining characterized the tumor as a B‐cell neoplasm with IgA heavy‐chain and lambda light‐chain restrictions. Complete remission of the disease occurred after surgery. The clinical, histologic, and immunohistochemical features of this lymphoma are suggestive of histogenetic derivation from mucosal‐associated tissue.

The nm23 gene is a putative tumour and metastasis suppressor gene. A number of studies have found that reduction of its expression is associated with increased metastatic potential in several human malignancies. Similarly, clinical studies have shown correlation between reduced nm23 protein expression and a poor prognosis. The aim of this study was to determine if a relationship exists between nm23 expression in primary cutaneous melanomas with or without cerebral metastases. Paraffin-embedded tissues were retrieved from 21 patients with primary cutaneous melanomas (n=21) and who subsequently developed cerebral metastases (n=24). Primary cutaneous melanomas with no regional or organ metastases within a 10 year period were used as control cases (n=34). Nm23 staining was localized in the cytoplasm of the tumour cells. Most of the control cases showed strong expression, whereas the majority of the primary melanomas with cerebral metastases showed no or weak expression of nm23. The cerebral metastases mostly showed strong expression. In summary, the results of this study may have significant prognostic implications for patients presenting with cutaneous melanoma. Patients with cutaneous melanomas with a low expression of nm23 appear to be more at risk of developing brain metastases.