European Journal of Cancer Prevention

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New information flows for cancer registries: testing the use of laboratory data in the province of Reggio Emilia, Italy

Haematological malignancies often escape the standard information flows of cancer registries because diagnosis is not always based on bone marrow histology but, rather, on other laboratory tests.
To quantify incident haematological malignancies identified exclusively through the laboratory information system and to measure the impact of that source on the sensitivity and accuracy of registering these malignancies.
We collected data from the only provincial laboratory of Reggio Emilia on molecular biology, flow cytometry tests and bone marrow smears to detect specific markers of some chronic haematological malignancies. We carried out a record linkage between laboratory reports (period 2013–2017) of patients resident in the province of Reggio Emilia and the Cancer Registry of Reggio Emilia.
Of the 303 patients who underwent at least one of these tests, 85 were not included in our Cancer Registry. Of these 85 patients, 42 had received a diagnosis of cancer: 34 myeloproliferative neoplasms, 3 chronic myeloid leukaemias, 3 myelodysplastic neoplasms, 1 multiple myeloma and 1 chronic lymphocytic leukaemia. We recovered 4.2% of the total number of chronic haemolymphopoietic cancers registered in the study period, accounting for 15% of myeloproliferative neoplasms. For 30% of prelinkage cases, the specificity of the morphological code improved.
Although the laboratory information system’s contribution to the completeness of Cancer Registry incident cases was modest, it is useful to add laboratory data to routine cancer registry information flows due to the increasing use of molecular characterisation and to the phenomenon of dehospitalisation.

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SETD2 as a regulator of N6-methyladenosine RNA methylation and modifiers in cancer

imageCancer is an unpleasant, painful disease. It is one of the most devastating diseases worldwide diminishing many lives. Many genetic and epigenetic changes occur before cancer develops. Mutation in SETD2 gene is one such example. RNA splicing, DNA damage repair, DNA methylation and histone methylation are some of the biological processes mediated by SETD2. SETD2 (histone H3 lysine 36 methyltransferase) is a frequently mutated gene in different types of cancer. Loss of SETD2 is associated with worse prognosis and aggressive phenotypes. Histone modification is one of the epigenetic regulation having a significant effect on gene regulation. N6-methyladenosine (m6A) mRNA modification is a well-known posttranscriptional modification playing a pivotal role in many normal and pathological processes affecting RNA metabolism. SETD2 catalyses H3K36 trimethylation and in turn H3K36me3 guides the deposition of m6A on nascent RNA transcripts. Finally, this review summarizes the deep understanding of the role of SETD2 in RNA methylation/modification and how SETD2 mutation contributes to tumour development.

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High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis

imageHigh mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating transcriptional activity of multiple genes indirectly through chromatin change and assembling enhanceosome. HMGA2 is overexpressed in multiple tumor types, suggesting its involvement in cancer initiation and progression, thus, making it an ideal candidate for cancer diagnostic and prognostic. We performed a systematic review to examine the role of HMGA2 as a universal tumor cancer diagnostic and prognostic marker. We used Reporting Recommendations for Tumor Marker Prognostic Studies to systematically search OvidMedline, PubMed, and the Cochrane Library for English language studies, published between 1995 and June 2019. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for an association between overall survival and recurrence of cancers for studies with available estimates. We identified 42 eligible studies with a total of 5123 tumor samples in 15 types of cancer. The pooled percentage of HMGA2 gene expression in tumor samples was 65.14%. Meta-analysis showed that cancer patients with HMGA2 positive have significantly reduced survival, compared to patients without HMGA2 gene [pooled-hazard ratio (HR) = 1.85, 95% CI 1.48–2.22]. There was a positive association between cancer patients with HMGA2 overexpression and cancer recurrence though this association did not reach significance (pooled-HR = 1.44, 95% CI 0.80–2.07). Overexpression of HMGA2 was found in 15 types of cancer. There was an association between HMGA2 overexpression with reduced survival of cancer patients. HMGA2 is thus considered a promising universal tumor marker for prognostics.

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HASPIN kinase inhibitor CHR-6494 suppresses intestinal polyp development, cachexia, and hypogonadism in Apcmin/+ mice

imageHASPIN has been identified as a nuclear Ser/Thr kinase specifically expressed in haploid germ cells. HASPIN kinase inhibitors were recently isolated, and their antitumor activity reported. Colorectal cancer occurs with high incidence worldwide. In this study, we examined whether HASPIN inhibitor CHR-6494 suppresses cancer progression in ApcMin/+ mice, a familial colon tumor disease model. Mice were treated by intraperitoneal injection of CHR-6494 for 50 days. Following the treatment period, intestinal polyps were counted and testosterone and spermatogenesis levels were observed. Intraperitoneal administration of CHR-6494 significantly inhibited intestinal polyp development and recovered body weight in ApcMin/+ mice. Although spermatogenesis was inhibited with increasing age in ApcMin/+ mice, CHR-6494 significantly improved blood testosterone levels and spermatogenesis. Our results suggest that HASPIN inhibitors may be useful as anti-cancer agents and for the treatment of hypogonadism in colorectal cancer patients.

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Outcomes and cost of lung cancer patients treated surgically or medically in Catalunya: cost–benefit implications for lung cancer screening programs

imageLung cancer screening programs with computed tomography of the chest reduce mortality by more than 20%. Yet, they have not been implemented widely because of logistic and cost implications. Here, we sought to: (1) use real-life data to compare the outcomes and cost of lung cancer patients with treated medically or surgically in our region and (2) from this data, estimate the cost–benefit ratio of a lung cancer screening program (CRIBAR) soon to be deployed in our region (Catalunya, Spain). We accessed the Catalan Health Surveillance System (CHSS) and analysed data of all patients with a first diagnosis of lung cancer between 1 January 2014 and 31 December 2016. Analysis was carried forward until 30 months (t = 30) after lung cancer diagnosis. Main results showed that: (1) surgically treated lung cancer patients have better survival and return earlier to regular home activities, use less healthcare related resources and cost less tax-payer money and (2) depending on incidence of lung cancer identified and treated in the program (1–2%), the return on investment for CRIBAR is expected to break even at 3–6 years, respectively, after its launch. Surgical treatment of lung cancer is cheaper and offers better outcomes. CRIBAR is estimated to be cost-effective soon after launch.

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Association between flavonoids, flavonoid subclasses intake and breast cancer risk: a case-control study in China

imageAnti-tumor effect of dietary flavonoids has been sustained by laboratory experiments, but epidemiological studies with breast cancer risk remained inconsistent and insufficient. This study aimed to investigate the associations between total and subclasses of flavonoid and breast cancer risk among Chinese population. This case-control study recruited 1522 eligible breast cancer cases and 1547 frequency-matched control subjects from June 2007 to July 2018 in Guangdong, China. Dietary intake was obtained by face-to-face interview using a validated food frequency questionnaire. Odds ratios and 95% confidence intervals were calculated by multivariable logistic regression models. After adjusting for potential confounders, inverse associations were observed between total flavonoids, anthocyanidins, proanthocyanidins, flavanones, flavones, flavonols and isoflavones and overall breast cancer risk. Comparing the highest versus the lowest quartile, odds ratio (95% confidence interval) was 0.66 (0.54–0.82) for total flavonoids, 0.61 (0.49–0.75) for anthocyanidins, 0.67 (0.54–0.83) for proanthocyanidins, 0.71 (0.57–0.88) for flavanones, 0.48 (0.39–0.60) for flavones, 0.51 (0.41–0.63) for flavonols and 0.67 (0.54–0.83) for isoflavones, respectively. No significant association was found between flavanols, flavan-3-ol monomers, theaflavins and breast cancer risk. Stratified analysis by menopausal status and estrogen receptor/progesterone receptor status showed that the associations of total flavonoids, most flavonoid subclasses with breast cancer risk were generally not modified by menopausal or estrogen receptor/progesterone receptor status. This study indicates that total flavonoids and most flavonoid subclasses intakes were inversely associated with breast cancer risk.

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Cesarean delivery may be protective against neoplasms of the uterine cervix in women of childbearing age

imageParity has been reported as a risk factor for cervical cancer. However, no study has investigated the risk of neoplasms of the uterine cervix according to the delivery type. We carried out a retrospective cohort study using nationwide data from the Korean Health Insurance Review and Assessment Database to investigate whether cesarean delivery might be associated with less development of neoplasms of the uterine cervix than a vaginal delivery in women of childbearing age. Women aged 20–44 years, who had undergone vaginal or cesarean deliveries in 2009 were included as subjects. Two individual datasets for carcinoma in situ (CIS) and cancer of the cervix were followed for 8 years until either disease outcomes or 31 December 2016. In total, 260 438 and 132 232 women had undergone vaginal only and cesarean only deliveries, respectively. There were 1505 and 423 new cases of CIS and cervical cancer, respectively, with median follow-up durations of 89.9 and 90.0 months for vaginal delivery and cesarean delivery, respectively. The unadjusted CIS risk ratio for cesarean delivery compared with vaginal delivery was 0.90 [95% confidence interval, (CI), 0.80–1.00]. After adjusting for categorical age, residential area, facility types, and number of visits to obstetrics and gynecology clinics, it was 0.83 (95% CI, 0.75–0.93). The unadjusted and adjusted risk ratios for cervical cancer for cesarean delivery were 0.98 (95% CI, 0.80–1.20) and 0.87 (95% CI, 0.71–1.08), respectively. Cesarean delivery may be more protective against CIS than vaginal delivery in women of childbearing age.

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Effectiveness of the cervical cancer prevention programme: a case-control mortality audit in Lithuania

imageThe cervical cancer burden in Lithuania has remained high, and there are no previous effectiveness studies of cervical cancer prevention programme in the country. We investigated the effect of a prevention programme on the risk of mortality from cervical cancer in Lithuania by conducting a mortality audit study. The register-based case-control study included 715 cervical cancer deaths that occurred during 2010–2015 in Lithuania and their 2145 matched controls. Screening histories for cases and controls were obtained from the National Health Insurance Fund database. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression and corrected for self-selection bias. Index screening was associated with a 56% reduction in the cervical cancer death risk, OR: 0.44; 95% CI 0.26–0.74. The ORs for stage I and stage II+ cancers were 0.80; 95% CI 0.32–2.00 and 0.36; 95% CI 0.21–0.62, respectively. The preventive effect was statistically significant for women aged ≥40 years, while nonsignificant for younger. In women who died of cervical cancer, 71% were not invited and 88% were not screened within the recommended 36 months prior to index date. Among cases with index invitation, 32% had index screening compared to 70% in controls. In conclusion, participation in screening has been effective in reducing cervical cancer mortality in Lithuania. The study shows poor screening attendance, emphasizing the importance of greater efforts at the national level to improve the effectiveness of the screening.

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Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population

imageEvaluation of the prevalence of POT1, ACD, and TERF2IP mutations among Polish melanoma patients. A cohort of 60 patients from melanoma-prone families, 1500 unselected cases and 1500 controls were genotyped. Methodology included Sanger sequencing, in-silico software predilection, and TaqMan assays. We identified three nonsynonymous variants: POT1 c.903 G>T; TERF2IP c.970 A>G; and ACD c.1544 T>C and a splice site variant ACD c.645 G>A. The c.903 G>T was predicted to be pathogenic according to PolyPhen-2, benign according to Mutation Taster, PROVEAN, AGVGD, and SIFT. The c.645 G>A was defined as disease caused by Mutation Taster and Human Splicing Finder and as variant of unknown significance by ClinVar. The other detected variants were described as benign. The c.903 G>T variant was present in two unselected cases and one control [P = 0.57, odds ratio (OR) = 2.00]; the c.645 G>A variant was not detected among the unselected cases and the controls; the c.970 A>G variant was present in 110 cases and 133 controls (P = 0.14, OR = 0.81); the c.1544 T>C variant was present in 687 cases and 642 controls (P = 0.11, OR = 1.07). We found no loss of heterozygosity of the c.903 G>T, c.970 A>G, and c.645 G>A variants. C.645 G>A variant had no effect on splicing or expression. The changes in POT1 c.903 G>T and ACD c.645 G>A can be classified as rare variants of unknown significance, the other variants appear to be polymorphisms. Germline mutations in POT1, ACD, and TERF2IP are infrequent among Polish melanoma patients.

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Association of poor mental health and skin cancer development: a cross-sectional study of adults in the United States

imageThe relationship between mental health and skin cancer is poorly characterized. This cross-sectional study used 2016 Behavioral Risk Factor Surveillance System data to evaluate the association between mental health problems and skin cancer development. Multivariate logistic regression analyses were performed to calculate adjusted odds ratio (aOR) for skin cancer development by mental health problems, adjusting for potentially confounding demographic and lifestyle factors. Odds of skin cancer were significantly higher in those with mental health problems problems [aOR 1.24, 95% confidence interval (CI) 1.17–1.31, P < 0.001]; this finding remained in sensitivity analysis adjusting for sunburn history (aOR 1.34, 95% CI 1.09–1.63, P = 0.004). Our findings reveal an association between poor mental health and increased skin cancer prevalence. The direction of this association is unclear. Distress of a skin cancer diagnosis may promote mental health problems, while, conversely, mental health problems may biologically potentiate skin cancer or be associated with risk factors like indoor tanning. Nevertheless, we demonstrate an elevated prevalence of mental health problems in patients with skin cancer.

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