Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma

The RIZ (PRDM2) locus commonly undergoes loss of heterozygosity (LOH) and maps within the minimal deleted region on 1p36 in hepatocellular carcinoma (HCC). Although peptide-altering mutations of RIZ are rare in HCC, the RIZ1 product is commonly lost in HCC and has tumour suppressive activities. Here, we analysed RIZ gene mutations and LOH in HCC, breast cancer, familial melanoma, colon cancer, and stomach cancer. We found 7 polymorphisms but no mutations. By analysing the Pro704-deletion polymorphism, we detected LOH of RIZ in 31 of 79 (39%) informative HCC cases, 11 of 47 (23%) colon cancer cases, 8 of 43 (19%) breast cancer cases, 8 of 66 (12%) stomach cancer cases. Importantly, loss of the Pro704+allele was found in 74% of the 31 LOH positive HCC cases (P< 0.01), indicating a preferential loss and hence a stronger tumour suppressor role for this allele compared to the P704−allele. In addition, the Pro704+allele was found to be more common in Asians (0.61) than Caucasians (0.42) (P = 0.0000), suggesting an interesting link between gene polymorphisms and potential differences in tumour incidence between racial groups. © 2001 Cancer Research Campaign http://www.bjcancer.co

Requirement of RIZ1 for cancer prevention by methyl-balanced diet

The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Unlike most of its related enzymes, RIZ1 was upregulated by methyl-balanced diet. Methyl-balanced diet did not fully repress oncogenes such as c-Jun in the absence of RIZ1. The data identify RIZ1 as a critical target of methyl-balanced diet in cancer prevention. The molecular understanding of dietary carcinogenesis may help people make informed choices on diet, which may greatly reduce the incidence of cancer

Markers for the identification of late breast cancer recurrence

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The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research

Retrospective analysis of molecular scores for the prediction of distant recurrence according to baseline risk factors

This work was funded by grants from Cancer Research UK (programme Grant C569-A16891), the Royal Marsden NIHR Biomedical Research Centre, and AstraZenec

Interaction effects of region-level GDP per capita and age on labour market transition rates in Italy

Abstract The aim of this paper is to measure the effect of the interaction between age for the population of males and females aged 18 to 74 and region-level GDP per capita on labour market transition probabilities in Italy. We compare different occupational states in a sample of males and females who remained in their region of residence at two points in time (12 months apart). We estimate the transition probabilities using a flexible hierarchical logit model with interaction effects between worker age and region-level GDP per capita. We apply this model using longitudinal data from the Italian Labour Force Survey that cover the 2004–2013 period. We find empirical support for the assumption that people in the same age cohort have different labour market opportunities based on the level of GDP per capita in their region of residence. These differences are particularly relevant among younger workers

Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature

Backgroundoverexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome.Methodsin all, 168 T1-3, N0-1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy.Resultsin the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7, P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03) and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively.Interpretationthe 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome