Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population‐based case–control study

Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population‐based case–control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967–2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78–0.97), gestational hypertension (OR 0.90; 95% CI 0.86–0.93) and preeclampsia (OR 0.91; 95% CI 0.88–0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98–1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.     

A gastrointestinal stromal tumor in the stomach: usefulness of computed tomographic volumetry

We report herein the case of a 70-year-old man who was found to have a gastrointestinal stromal tumor (GIST) in the stomach following sigmoid colon resection. Preoperative gastroscopic and barium examinations revealed a submucosal tumor, measuring 10cm, on the upper part of the stomach. Using computed tomography (CT) images (i.e., computed tomographic volumetry) the doubling time of this tumor was calculated, accurately, as 3.3 months, which suggested a high growth rate and malignancy. A laparotomy and partial gastric resection were performed. Histologically, the tumor consisted of spindle-shaped cells with oval nuclei. In immunohistochemical studies, the tumor cells were positive with respect to c-kit, CD34, and vimentin, but negative with respect to smooth muscle actin and S-100 protein. There were 15–16 mitoses per 50 high-power fields (HPFs), and the Ki-67 antigen (MIB-1) index was 25.5% in the most active areas, which also indicated malignancy. The final pathological diagnosis of this tumor was malignant GIST. The patient was found to have hepatic metastasis 27 months after the surgery, and he subsequently received a hepatic subsegmentectomy. To our knowledge, there are very few reports concerning the growth rate of GISTs. Computed tomographic volumetry is useful for the follow-up of small or irregularly shaped gastric submucosal tumors, and for making decisions regarding surgical intervention.     

Distance from residence to power line and risk of childhood leukemia: a population-based case–control study in Denmark

Purpose

Epidemiological studies have found an association between exposure to extremely low-frequency magnetic fields (ELF-MF) and childhood leukemia. In 2005, a large British study showed an association between proximity of residence to high-voltage power lines and the risk of childhood leukemia. The association extended beyond distances at which the ‘power line’-induced magnetic fields exceed background levels, suggesting that the association was not explained by the magnetic field, but might be due to chance, bias, or other risk factors associated with proximity to power lines. Our aim was to conduct a comparable study in an independent setting (Denmark).

Methods

We included 1,698 cases aged <15, diagnosed with leukemia during 1968–2006, from the Danish Cancer Registry and 3,396 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132–400 kV overhead power line.

Results

Odds ratios (ORs) were 0.76 [95 % confidence interval (CI) 0.40–1.45] for children who lived 0–199 m from the nearest power line and 0.92 (95 % CI 0.67–1.25) for those who lived 200–599 m away when compared with children who lived ≥600 m away. When restricting the analysis to 220 and 400 kV overhead power lines, the OR for children who lived 200–599 m from a power line was 1.76 (95 % CI 0.82–3.77) compared to children who lived ≥600 m away. However, chance is a likely explanation for this finding as the result was not significant, numbers were small, and there were no indications of an higher risk closer to the lines since no cases were observed within 200 m of these.

Conclusions

We found no higher risk of leukemia for children living 0–199 m or for children living 200–599 m of a 132–400 kV overhead power line. A slightly elevated OR for children living between 200 and 599 m of a 220–400 kV overhead power line is likely to be a chance finding.     

Posttraumatic distress symptoms in operable breast cancer III:

One hundred and six patients with operable breast cancer were studied at intervals one day before surgery, and at six weeks and one year post-operatively by means of taped clinical interviews and self-report questionnaires (Impact of Event Scale (IES) and General Health Questionnaire (GHQ-28)). A year after surgery, 9%reported a high level of intrusive symptoms and 10% of avoidance symptoms compared to 18% and 14% after six weeks, respectively. Based on questionnaire data, a year after surgery, thirteen patients (12%) were estimated to have a posttraumatic stress disorder (PTSD) compared to fifteen patients (14%) after six weeks. Severity of posttraumatic stress symptoms (PTSS) after one year was significantly associated with impaired psychosocial functioning over the last year previous to surgery (p < 0.05), negative life events during the year before surgery (p < 0.05), health problems during the previous ten years (p < 0.01), and a personality trait characterized by high emotional reactivity (p < 0.001). Crisis support in the acute situation, type of surgery, axillary-node metastases, and postoperative adjuvant chemotherapy did not predict subsequent PTSS. Premorbid health variables, personality, and level of distress six weeks after surgery were most important risk factors for persistent PTSS in our patients with operable breast cancer stage I and II.     

NET‐producing CD16high CD62Ldim neutrophils migrate to tumor sites and predict improved survival in patients with HNSCC

The concept of functional neutrophil subsets is new and their clinical significance in malignancies is unknown. Our study investigated the role of CD16^dim CD62L^high, CD16^high CD62L^high and CD16^high CD62L^dim neutrophil subsets in head and neck squamous cell carcinoma (HNSCC) patients. These neutrophil subsets may play different roles in immune‐related activity in cancer, based on their profile, activation state and migration ability within a tumor site, which may be important in predicting cancer prognoses. Tumor biopsies and blood were obtained from newly diagnosed untreated HNSCC patients and healthy controls. Neutrophil subsets and their phenotype were characterized using flow cytometry. Isolated granulocytes were assessed for anti‐tumor immune functions. Compared to controls HNSCC patients exhibited increased CD16^high CD62L^dim neutrophils in blood; this subset displayed a distinct phenotypes with high expression of CD11b and CD18. This subset was prone to migrate into the tumor facilitated by tumor‐derived IL‐8. Furthermore, IL‐8 was also found to activate neutrophils and thereby promoting subset transition. Various assays demonstrated that activated CD16^high CD62L^dim neutrophils inhibited migration, proliferation and induced apoptosis of FaDu cancer cells. Neutrophil elastase detected in activated CD16^high CD62L^dim neutrophils and tumor biopsies suggested that CD16^high CD62L^dim neutrophils impart anti‐tumoral activity via neutrophil extracellular traps. Furthermore, increased fraction of CD16^high CD62L^dim neutrophils was shown to correlate with an increased survival rate. Our study demonstrates the clinical relevance of the CD16^high CD62L^dim neutrophil subset, providing evidence for its increased migration capacity, its anti‐tumor activity including increased NET formation and finally its correlation with increased survival in HNSCC patients.     

抑癌基因PTEN依赖其磷酸活性诱导人膀胱癌细胞BIU-87失巢凋亡机制

Objective： To investigate the effects and mechanisms of tumor suppressor gene PTEN on the induction of anoikis of human bladder transitional carcinoma cells BIU-87. Methods： BIU-87 cells were transfected with GFP plasmids containing wild-type PTEN or phosphatase inactivating mutant PTEN （C124A-PTEN） in vitro. The PTEN expression and the phosphorylation levels of focal adhesion kinase （FAK） and protein kinase B （PKB/Akt） were detected by Western blotting. Flow cytometry assay and laser scanning confocal microscopy were used to analyze apoptosis in adherent and non-adherent cells. Results： Compared with the control group; PTEN expression in the cells transfected with wild-type PTEN increased to 210%-260%, while the phosphorylation level of FAK and Akt decreased 59% （ P 〈 0.01） and 89% （ P 〈 0.01）, respectively. And the anoikis percentage increased from 8,32 ± 0.57% to 37.62 ± 2.12%, In the cells transfected with C124A-PTEN, neither the phosphorylation of FAK and Akt nor the anoikis percentage had obviously changed, although the PTEN expression enhanced remarkably in comparison with the control. Conclusion： Through its phosphatase activity, tumor suppressor gene PTEN can suppress the phosphorylation of FAK and Akt, and induce anoikis in human bladder transitional carcinoma cells BIU-87.     

Correlation between the gene expression profiles of adenocarcinoma of esophagus and Barrett＇s esophagus

Objective  

The aim of this study was to investigate the characteristics of gene changes from Barrett’s esophagus (BE) to esophageal adenocarcinoma by cDNA microarray.     

High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

Background:

Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m⁻²) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer.

Patients and methods:

In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up.

Results:

High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact.

Conclusion:

High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied.