What's new?

Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by HR+ tumor subtypes as defined by histologic grade and proliferation level. In this report pooling risk factor data from a consortium of breast cancer studies, the authors found associations between nulliparity and highly proliferative tumors; obesity and high grade tumors; and current use of combined hormone therapy and low grade tumors. These results provide insights into heterogeneity of HR+ tumors that may be reflective of differences in etiological pathways, and could also have implications for risk prediction of aggressive subtypes of HR+ tumors.

What's new?

Salivary duct carcinoma (SDC) is a rare and often fatal malignancy. Little is known about associations between its pathological features and clinical outcome. In this study, clinicopathological factors were analyzed for 177 patients diagnosed with SDC in The Netherlands between 1990 and 2014. The data show that median overall survival (OS) and distant metastasis-free survival (DMFS) were 51 and 26 months, respectively. At diagnosis, 68% of patients presented with lymph node metastases. Lymph node positivity was associated with poor OS and poor DMFS. The absolute number of metastatic lymph nodes was the only significant prognostic factor for survival in a multivariate analysis. Androgen receptor and human epidermal growth factor 2 (HER2) were positive in 96% and 29%, respectively and were not a prognostic factor.

What's new?

The incidence of testicular germ cell tumors (TGCTs) is rising, particularly among men of Northern European descent. Although TGCT risk has been suggested to be determined in early life, few early risk factors have been identified. This study examined the relationship between TGCT and childhood height, which is influenced by a combination of genetics, health and nutrition. Height was found to be associated with TGCT risk by age 7, with risk being lowest for the shortest boys. The findings suggest that TGCT risk is established in early life, though the mechanism behind this phenomenon requires further investigation.

What's new?

Eating red meat may affect one's risk of colon cancer. Here, the authors looked for a relationship between colorectal cancer risk and red meat, poultry, fish, and vegetarian diets. They used data from the UK Womens Cohort study, with dietary information collected by survey. No statistically significant association was found for total CRC risk, but when they looked at specific cancer sub-sites, a correlation emerged. Although numbers were small, a reduction in distal CRC risk was observed among those who did not eat red meat. A larger study would be desirable to confirm these findings.

What's new?

Although the link of preeclampsia and hyperemesis gravidarum with altered sex hormone levels is well established, relatively little is known about the association of these pregnancy complications with breast cancer risk. Here, the authors found that a history of preeclampsia decreased the risk of premenopausal breast cancer and tumors enriched for the receptor tyrosine-protein kinase HER2. In contrast, hyperemesis gravidarum increased the risk to develop HER2-enriched tumors, pointing to nuanced differences of sex hormone alterations during pregnancy with respect to breast cancer subtypes and menopausal status.

What's new?

The question whether and how diabetes affects cancer risk remains controversial. The authors analyzed data from the Swedish Twin Registry and found that midlife diabetes increased risk of cancers in the pharynx, small intestine and liver. Interestingly, diabetes also reduced risk of prostate cancer, an effect that may be partially buffered by genetic and early-life influences. The authors recommend screening programs to prevent late-life cancer development in individuals with diabetes.

What's new?

Pancreatic cancer (PC) has been associated with alcohol consumption but studies are inconsistent and hampered by low numbers of incident events. Here, the authors studied more than 1000 PC cases and found that baseline and lifetime alcohol intakes were positively related to PC, with stronger risks for beer and spirit than wine intake. Associations were not modulated by smoking habits, underscoring the role of alcohol as a potential carcinogen for PC.

What's new?

OncoE6, an immunoassay detecting the oncogenic E6 protein from human papilloma virus (HPV) type 16 and 18, is a rapid, simple and affordable HPV test. Here the authors report that OncoE6 – while less sensitive than PCR-based HPV detection – was more specific in patients with high-grade cervical intraepithelial neoplasia. The authors consider E6 as a useful tool for cervical cancer screening and also a potential biomarker for cervical lesion progression.

What's new?

Background parenchymal enhancement (BPE) on breast MRI is an emerging marker of breast cancer risk. Both MRI-density, an established risk factor, and BPE are knwon to be sensitive to hormonal exposures, but the relationship between MRI-density, BPE, and serum hormone levels remains unstudied. Here, no significant associations between MRI-density and serum E1, E2 and bioavailable E2 were observed after adjustment for body mass index in postmenopausal women without cancer. Serum estrogen concentrations were, however, positively associated with BPE, providing further evidence of its hormone-sensitive nature, and suggesting its potential role as an imaging marker of hormonal exposures in the breast.

What's new?

Esophageal and gastric cancers occur more frequently in men than women. While these malignancies have been associated with hormonal and reproductive factors in women, whether such associations also exist in men is unclear. The authors of the present study investigated potential links between upper gastrointestinal cancer risk and male hormonal and reproductive factors in men enrolled in the UK Biobank prospective study. Only male pattern baldness was associated with gastric cancer risk. The relationship was strongest for frontal male pattern baldness. The findings warrant further investigation for possible relationships between hormone levels and upper gastrointestinal cancer risk.

What's new?

The value of breast cancer screening is still under debate. To date, most observational studies have reported the incidence of early and advanced breast cancer without differentiating by screening status. This study compared the age-specific incidence rates of early and advanced breast cancer among attenders and non-attenders of a fully implemented, steady-state screening program based on individual screening status and background incidence of breast cancer. There was a significantly lower incidence of advanced breast cancer in patients who attended screening compared with patients who did not. Breast cancer screening is associated with earlier stage at diagnosis, which should improve outcomes.

What's new?

While it is known that infection with human papilloma virus (HPV) type 16 can lead to highest-grade cervical intraepithelial neoplasia (CIN3+), the HPV types associated with progression to the less dysplastic CIN2+ stage are less well studied. Here the authors analyzed data from a national screening program in Norway and found that HPV35, along with HPV31 and 33, was quite common with a CIN2+ progression risk similar to HPV16. However, HPV16 had the strongest association with progression to CIN3+, underscoring the heterogeneity observed in the CIN2+ progression risk group.

What's new?

Taking samples in the privacy of one's own home (self sampling) makes it possible to reach non-attendees of medical screening programs such as those for cervical human papilloma virus (HPV) infection. The authors evaluated the effectiveness of two different strategies of offering an HPV-self sampling program, and compared these strategies with the standard recall letter or no intervention at all. Their results support the efficacy of a self-sampling strategy particularly in postmenopausal non-responders. Future research should focus on the performance of different self-sampling devices in post-menopausal women as low DNA concentrations exponentially increased over age.

What's new?

Liver cancer represents a leading cause of cancer-related mortality in West Africa. While hepatitis B virus has been previously identified as the major contributor to liver cancer in this endemic region, limited information is available on other risk factors. Here, the authors conducted a case–control study in hospitals in Côte d'Ivoire, Mali and Togo. Aside the independent association of alcohol use and HBV and HCV infection with liver cancer, a synergic effect between alcohol use and HBV infection was identified. Timely screening and care of HBV infection and hazardous drinking might significantly curb HCC in West Africa.

What's new?

Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, germline-somatic interactions in lung cancer largely remain unknown. Here, the authors investigated whether lung cancer driver genes (CDGs) were more likely to locate within cancer susceptibility regions. They found that CDGs were enriched in cancer susceptibility regions. Lung cancer susceptibility genes and CDGs were both enriched in nine pathways. Further analysis associated risk SNPs with somatic mutations at the level of genes, pathways, and APOBEC mutagenesis. These results indicate germline-somatic interactions in lung tumorigenesis, and help to uncover the molecular mechanisms underlying lung cancer risk SNPs.

What's new?

Free fatty acid receptor 2 (FFAR2) is involved in colonic inflammation. However, it remains unclear whether FFAR2 is an epigenetic regulator that suppresses colon tumorigenesis. This study suggests that loss of FFAR2 epigenetically promotes colon cancer development. The authors found in FFAR2-deficient mice that the downstream cAMP–PKA–CREB–HDAC pathway was enhanced. H3K27me3 and H3K4me3 histone marks differentially bound onto the promoter regions of inflammation suppressors, resulting in their lower expression. More neutrophils infiltrated into tumors and colonic lamina propria. FFAR2 is required for butyrate, a natural ligand of FFAR2, to suppress HDAC expression and hypermethylation of inflammation suppressors.

What's new?

Prostate cancer patients who also have metabolic syndrome often find their cancers more aggressive. A new study examines the molecular link between metabolic syndrome and cancer. According to previous results, a lack of the transcriptional corepressor CTBP1 hinders the growth of prostate cancer. In this study, the authors looked at whether CTBP1 influences expression of the tumor suppressor CLCA2. They found that CTBP1 stopped transcription of CLCA2 by binding to its promoter. In mice with metabolic syndrome given cancers cells that lacked CLCA2, more circulating tumor cells arose than in mice with control tumors, suggesting that suppressing CLCA2 expression promotes EMT.

What's new?

Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while genetic alterations are already used as prognostic and predictive biomarkers, epigenetic alterations are less well characterized. Here, the authors identified and validated a panel of 74 altered CpG islands able to discriminate CRCs and adenomas from peritumoral and normal mucosa with very high specificity and sensitivity. Three selected markers were tested and detected through non-invasive techniques, both in circulating tumor DNA and in stool DNA. The earliest methylation alterations affected genes coding for proteins involved in the crosstalk between tumor cells and their surrounding environment.

What's new?

The main function of caspase-3 is to eliminate damaged cells. Following activation, it cleaves proteins vital to cell function, thereby fueling apoptosis. As a result, caspase-3 generally is thought to be a beneficial factor in cancer therapy. This study shows, however, that caspase-3 plays important roles in promoting colon cancer cell invasion and metastasis. Compared to control cells, caspase-3 knockout colon cancer cells (CASP3KO) demonstrated significantly reduced invasive potential in vitro. In vivo, tumors formed by CASP3KO cells exhibited increased sensitivity to radiotherapy and reduced metastatic tendency. The findings suggest that caspase-3 is a potential target for colon cancer therapy.

What's new?

Drugs that block the immune-checkpoint protein PD-L1 have potent antitumor effects. They also increase expression of interferon-γ (IFN-γ). In this study, the authors found that patients whose tumors expressed both IFN-γ and PD-L1 had a more favorable prognosis than those that expressed IFN-γ alone. Co-expression of these molecules may thus serve as a biomarker for a tumor's sensitivity to IFN-γ. The study also analyzed the JAK2-STAT1 and PI3K-AKT pathways in these tumors. Further understanding of how these pathways interact with IFN-γ might offer novel approaches to targeted therapy and immunotherapy.

What's new?

Little is known about the contribution of microRNA dysregulation to the pathogenesis of adrenocortical carcinoma (ACC), a highly aggressive malignancy. This work provides first evidence that two overexpressed microRNAs, miR-483-5p and miR-139-5p, respectively target two members of the N-myc downstream-regulated gene family, NDRG2 and NDRG4. Key factors mediating epithelial-to-mesenchymal transition are downstream effectors of miR-483-5p/NDRG2 and miR-139-5p/NDRG4 pathways. miR-483-5p and miR-139-5p promote ACC migration and invasion by suppressing NDRG2 and NDRG4 expression. Both target genes are strikingly under-expressed in patients with aggressive tumors. Thus, miR-483-5p/NDRG2 and miR-139-5p/NDRG4 axes may represent novel targets for therapeutic intervention in ACC with poor outcome.

What's new?

In search of new inroads against chronic lymphocytic leukemia, these authors turned to the NOTCH1 signalling pathway. Could inhibiting NOTCH1 help treat CLL? To find out, they first identified the calcium channel blocker bepridil as a NOTCH1 inhibitor. Next, they showed that bepredil induced apoptosis in isolated CLL cells, regardless of whether they bore NOTCH1 mutations. In mice bearing CLL cells, bepredil inhibited the proliferation of the tumor cells with no overt signs of toxicity. Thus, it seems advisable to pursue bepredil as a possible candidate for treating CLL.

What's new?

In addition to lowering cholesterol, statins may reduce the risk of several cancers. The impact of these drugs on non-Hodgkin lymphoma (NHL) has been unclear, however. In this study, the authors examined associations between different types of statins and various subtypes of NHL. They found that high-potency and highly lipophilic statins were associated with reduced risk of diffuse large B-cell lymphomas (DLBCL) and plasma cell lymphomas, but not other NHL types. Further studies are needed to verify these associations and to understand the underlying mechanisms.

What's new?

The root of the Tsoong herb or C. cordifolioidea has been used as a herbal remedy in the Chinese Yunnan province since ancient times. Here the authors studied the effect of verbascoside, a major bioactive constituent of Tsoong, in human oral squamous cell carcinoma (OSCC). They find that verbascoside inhibited cell growth and promoted apoptosis in in vitro and in vivo models of OSCC by interfering with the activation of the transcription factor NF-κB, pointing to a potential therapeutic function of verbascoside or Tsoong in OSCC patients.

What's new?

Targeting metabolic dependencies of tumor cells has emerged as a promising new therapeutic approach. Here the authors used an approved anti-obesity drug, orlistat, as an adjuvant treatment for platinum-resistant ovarian cancer. They show that in mice addition of orlistat re-sensitises tumors to cisplatin therapy and speculate that the combination of orlistat and cisplatin could be used clinically to treat patients with platinum-refractory ovarian cancer.