<Emphasis Type="Italic">ABI3</Emphasis> ectopic expression reduces <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>cell growth properties while inducing senescence

Background  

Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown.     

Comprehensive analysis of <Emphasis Type="Italic">NuMA</Emphasis>variation in breast cancer

Background  

A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer.     

Analysis of large deletions in <Emphasis Type="Italic">BRCA1</Emphasis>, <Emphasis Type="Italic">BRCA2</Emphasis> and <Emphasis Type="Italic">PALB2</Emphasis> genes in Finnish breast and ovarian cancer families

Background  

BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families.     

Post‐operative stereotactic radiotherapy for the treatment of intracranial haemangiopericytoma: ‘A Study of Dose and Outcome’

Introduction

This study was performed to assess the relationship between tumour response and radiation dose in equivalent 2 Gy per fraction (EQD2).

Method

A retrospective cohort analysis of 21 patients with a diagnosis of intracranial haemangiopericytoma between 2000 and 2013 was included in this study. A total of 39 lesions were analysed. The equivalent dose in 2 Gy per fraction was calculated by assigning an alpha–beta ratio of 12 Gy. A paired t‐test compared dose (EQD2) and tumour response, and as the outcome was binary, a logistic regression analysis was performed.

Results

In total, there were 14 cases of progression and 25 cases of non‐progression. It was estimated that for a one unit increase in EQD2, the odds of non‐progression were increased by a factor of 1.13 (P = 0.026). After adjusting for PTV volume, the estimated effect of EQD2 (min) on tumour response was stronger, with an estimated odds ratio of 1.36 for an increase of one unit and an odds ratio of 21.6 for an increase of 10 units (P = 0.015). The dose range varied with varying PTV volumes. Based on the logistic model, the probability of having non‐progression is larger than 50% for EQ2Dmin doses larger than 30–40 Gy, in particular for volumes larger than 3.67 cm³.

Conclusion

This study demonstrates that there is a relationship between dose (EQD2) and outcome. With increasing dose, the likelihood of regression is higher. When adjusted for PTV volume, the response appeared stronger. The dose varied significantly with changes in the size of the PTV.     

<Emphasis Type="Italic">ErbB3</Emphasis> is required for ductal morphogenesis in the mouse mammary gland

Introduction  

The receptor ErbB3/HER3 is often over-expressed in human breast cancers, frequently in conjunction with over-expression of the proto-oncogene ERBB2/HER2/NEU. Although the prognostic/predictive value of ErbB3 expression in breast cancer is unclear, ErbB3 is known to contribute to therapeutic resistance. Understanding ErbB3 functions in the normal mammary gland will help to explain its role in cancer etiology and as a modulator of signaling responses to the mammary oncogene ERBB2.     

<Emphasis Type="Italic">MGMT</Emphasis> promoter methylation,loss of expression and prognosis in 855 colorectal cancers

Objective  

O ⁶-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme. MGMT promoter hypermethylation and epigenetic silencing often occur as early events in carcinogenesis. However, prognostic significance of MGMT alterations in colorectal cancer remains uncertain.     

High resolution melting analysis for rapid and sensitive <Emphasis Type="Italic">EGFR</Emphasis> and <Emphasis Type="Italic">KRAS</Emphasis> mutation detection in formalin fixed paraffin embedded biopsies

Background  

Epithelial growth factor receptor (EGFR) and KRAS mutation status have been reported as predictive markers of tumour response to EGFR inhibitors. High resolution melting (HRM) analysis is an attractive screening method for the detection of both known and unknown mutations as it is rapid to set up and inexpensive to operate. However, up to now it has not been fully validated for clinical samples when formalin-fixed paraffin-embedded (FFPE) sections are the only material available for analysis as is often the case.     

Squamocin modulates histone H3 phosphorylation levels and induces G<Subscript>1</Subscript> phase arrest and apoptosis in cancer cells

Background  

Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected aurora B and MSK1 as representatives for testing various compounds and drugs, and found that squamocin, a bis-tetrahydrofuran annonaceous acetogenin, exerted a potent effect on histone H3 phosphorylation.     

Polymorphisms of the <Emphasis Type="Italic">XRCC1</Emphasis>, <Emphasis Type="Italic">XRCC3</Emphasis>, &; <Emphasis Type="Italic">XPD</Emphasis>genes,and colorectal cancer risk: a case-control study in Taiwan

Background  

Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer.     

High resolution melting for mutation scanning of <Emphasis Type="Italic">TP53</Emphasis>exons 5–8

Background  

p53 is commonly inactivated by mutations in the DNA-binding domain in a wide range of cancers. As mutant p53 often influences response to therapy, effective and rapid methods to scan for mutations in TP53 are likely to be of clinical value. We therefore evaluated the use of high resolution melting (HRM) as a rapid mutation scanning tool for TP53 in tumour samples.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.     

Characterisation of prostate cancer lesions in heterozygous <Emphasis Type="Italic">Men1</Emphasis> mutant mice

Background  

Mutations of the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that Men1 disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the Men1 mutant mice.     

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and cancer risk: A systematic review and meta-analysis

Background

The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A systematic review and meta-analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted.

Methods

MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta-analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1-point increment) and categorical (highest vs. lowest score category) variable using random-effects models were estimated.

Results

Eighteen studies (11 cohort; seven case-control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1-point increment in adherence score was 0.89 (95% CI, 0.85–0.93; I² = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84–0.91; I² = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86–0.98, I² = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta-analysis results using categorical adherence score variables were consistent with these findings.

Conclusions

Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted.

PROSPERO registration number

CRD42022313327.     

Simplifying the detection of <Emphasis Type="Italic">MUTYH</Emphasis> mutations by high resolution melting analysis

Background  

MUTYH-associated polyposis (MAP) is a disorder caused by bi-allelic germline MUTYH mutation, characterized by multiple colorectal adenomas. In order to identify mutations in MUTYH gene we applied High Resolution Melting (HRM) genotyping. HRM analysis is extensively employed as a scanning method for the detection of heterozygous mutations. Therefore, we applied HRM to show effectiveness in detecting homozygous mutations for these clinically important and frequent patients.     

Promoter hypermethylation of the <Emphasis Type="Italic">SFRP2</Emphasis> gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

Background  

We have previously reported that expression of the Wnt antagonist genes SFRP1 and SFRP5 is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether SFRP2 promoter methylation might serve as a potential tumor biomarker.     

<Emphasis Type="Italic">PTTG</Emphasis>/securin activates expression of <Emphasis Type="Italic">p53</Emphasis> and modulates its function

Background  

Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed abundantly in most tumors. Overexpression of PTTG induces cellular transformation and promotes tumor formation in nude mice. PTTG has been implicated in various cellular processes including sister chromatid separation during cell division as well as induction of apoptosis through p53-dependent and p53-independent mechanisms. The relationship between PTTG and p53 remains unclear, however.     

Genetic variants in <Emphasis Type="Italic">MMP9</Emphasis> and <Emphasis Type="Italic">TCF2</Emphasis> contribute to susceptibility to lung cancer

Objective|  

The Wnt signaling pathway is crucial for pulmonary development and differentiation; dysregulation of the Wnt signaling pathway may impair lung function. Indeed, single nucleotide polymorphisms (SNPs) of Wnt pathway-related genes have been suggested as risk factors for certain types of cancers. In this study, we aimed to evaluate the influence of SNPs in Wnt-related genes (TCF2, MMP9) on susceptibility to lung cancer.     

Polymorphisms in the cytochrome <Emphasis Type="Italic">P</Emphasis>450 genes <Emphasis Type="Italic">CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1</Emphasis>, <Emphasis Type="Italic">CYP19A1</Emphasis>and colorectal cancer risk

Background  

Cytochrome P 450 (CYP) enzymes have the potential to affect colorectal cancer (CRC) risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones.     

Non‐small cell lung cancer brain metastasis screening in the era of positron emission tomography‐CT staging: Current practice and outcomes

Introduction

Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non‐small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET‐CT).

Methods

We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET‐CT to stage extra‐cranial disease. BMS was defined as dedicated brain imaging with contrast‐enhanced computed tomography (CE‐CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits.

Results

A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE‐CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non‐brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N‐stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T‐stage (P = 0.001), N‐Stage (P < 0.001) and overall stage (P < 0.001).

Conclusions

Non‐small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system.