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It is quite well documented that the COVID-19 pandemic disrupted cancer screening services in all countries, irrespective of their resources and healthcare settings. While quantitative estimates on reduction in volume of screening tests or diagnostic evaluation are readily available from the high-income countries, very little data are available from the low- and middle-income countries (LMICs). From the CanScreen5 global cancer screening data repository we identified six LMICs through purposive sampling based on the availability of cancer screening data at least for the years 2019 and 2020. These countries represented those in high human development index (HDI) categories (Argentina, Colombia, Sri Lanka, and Thailand) and medium HDI categories (Bangladesh and Morocco). No data were available from low HDI countries to perform similar analysis. The reduction in the volume of tests in 2020 compared to the previous year ranged from 14.1% in Bangladesh to 72.9% in Argentina (regional programme) for cervical screening, from 14.2% in Bangladesh to 49.4% in Morocco for breast cancer screening and 30.7% in Thailand for colorectal cancer screening. Number of colposcopies was reduced in 2020 compared to previous year by 88.9% in Argentina, 38.2% in Colombia, 27.4% in Bangladesh, and 52.2% in Morocco. The reduction in detection rates of CIN 2 or worse lesions ranged from 20.7% in Morocco to 45.4% in Argentina. Reduction of breast cancer detection by 19.1% was reported from Morocco. No association of the impact of pandemic could be seen with HDI categories. Quantifying the impact of service disruptions in screening and diagnostic tests will allow the programmes to strategize how to ramp up services to clear the backlogs in screening and more crucially in further evaluation of screen positives. The data can be used to estimate the impact on stage distribution and avoidable mortality from these common cancers.

Significance In cancer, the metabolism of copper and sulfur are dysregulated, leading to deleterious side effects. These issues are commonly addressed by studying the variations of concentrations of the elements, but here we have used, for the first time to our knowledge, copper and sulfur stable isotope compositions variations, using methods widespread in Earth sciences. We show that in hepatocellular carcinomas patients, blood copper and sulfur are enriched in light isotopes compared with control subjects. These isotopic signatures are not compatible with a dietary origin, but rather reflect the massive reallocation in the body of copper immobilized within cysteine-rich proteins such as metallothioneins. We also propose that sulfur isotope compositions could serve to track sulfur originating from tumor-derived sulfides. The widespread hypoxic conditions of the tumor microenvironment can impair the metabolism of bioessential elements such as copper and sulfur, notably by changing their redox state and, as a consequence, their ability to bind specific molecules. Because competing redox state is known to drive isotopic fractionation, we have used here the stable isotope compositions of copper ( ⁶⁵Cu/ ⁶³Cu) and sulfur ( ³⁴S/ ³²S) in the blood of patients with hepatocellular carcinoma (HCC) as a tool to explore the cancer-driven copper and sulfur imbalances. We report that copper is ⁶³Cu-enriched by ∼0.4‰ and sulfur is ³²S-enriched by ∼1.5‰ in the blood of patients compared with that of control subjects. As expected, HCC patients have more copper in red blood cells and serum compared with control subjects. However, the isotopic signature of this blood extra copper burden is not in favor of a dietary origin but rather suggests a reallocation in the body of copper bound to cysteine-rich proteins such as metallothioneins. The magnitude of the sulfur isotope effect is similar in red blood cells and serum of HCC patients, implying that sulfur fractionation is systemic. The ³²S-enrichment of sulfur in the blood of HCC patients is compatible with the notion that sulfur partly originates from tumor-derived sulfides. The measurement of natural variations of stable isotope compositions, using techniques developed in the field of Earth sciences, can provide new means to detect and quantify cancer metabolic changes and provide insights into underlying mechanisms.

To identify the situation and possible work-related cancer risks among healthcare workers in cancer centers. This research was a 14-year retrospective cohort study of 2,331 healthcare workers at the National Cancer Institute and 7 regional cancer centers in Thailand. The study period consisted of a total of 18,939 person-years of observation. The demographic data, such as occupation and work area were collected by self-administered questionnaires or by use of a proxy. The cases were identified by the diagnoses of physicians. The incidence rates for each type of cancer, occupation and work area among the population of this study were compared with the general working population, based on national cancer statistics. The results were reported in terms of Standard Incidence Ratio (SIR) and a 95% confidence interval (CI), using Fisher's exact method. There were 12 different types of cancer identified in 35 cases during the 14 years of the study and breast cancer was found to be at the highest number. The overall cancer incidence rates were 221.04 and 173.43 per 100,000 person-years, in males and females, respectively. Leukemia showed statistically significant levels of high SIR among the female healthcare staffs (SIR = 11.54; 95% CI = 2.38-33.72). With regard to occupation, only the male physicians showed significant SIR = 6.02; 95% CI = 1.41-19.93, while this study did not identify significant SIR levels in any of the work areas. This study found that the risk of leukemia was higher than expected among healthcare workers and that physicians may have an increased risk of cancer compared to the general working population, which may be a work-related reflex. However, interpretations should be made with caution due to the small number of cases.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor sequencing to assess methylation on a panel of genes (FBLN1, HINT2, LAMC1, LTBP1, LTBP2, PSMA2, PSMA7, PXDN, TGFB1, UBE2L3, VIM and YWHAZ) in plasma circulating cell-free DNA (cfDNA) and to evaluate the potential of these genes as HCC biomarkers in two different series, one from France (42 HCC cases and 42 controls) and one from Thailand (42 HCC cases, 26 chronic liver disease cases and 42 controls). We also analyzed a set of HCC and adjacent tissues and liver cell lines to further compare with 'The Cancer Genome Atlas' (TCGA) data. The methylation in cfDNA was detected for FBLN1, PSMA7, PXDN and VIM, with differences in methylation patterns between cases and controls for FBLN1 and VIM. The average methylation level across analyzed CpG-sites was associated with higher odds of HCC for VIM (1.48 [1.02, 2.16] for French cases and 2.18 [1.28, 3.72] for Thai cases), and lower odds of HCC for FBLN1 (0.89 [0.76, 1.03] for French cases and 0.75 [0.63, 0.88] for Thai cases). In conclusion, our study provides evidence that changes in VIM and FBLN1 methylation levels in cfDNA are associated with HCC and could represent useful plasma-based biomarkers. Also, the potential to investigate methylation patterns in cfDNA could bring new strategies for HCC detection and monitoring high-risk groups and response to treatment.

Background Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. Methods We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. Results We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P  < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15–3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively. Conclusion Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.

Dietary folate as well as polymorphic variants in one-carbon metabolism genes may modulate risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Alcohol is well recognized as a risk factor for breast cancer, and interactions with one-carbon metabolism has also been suggested. The purpose of this study is to test the hypothesis that genetic polymorphisms in the folate and alcohol metabolic pathway are associated with breast cancer risk. Twenty-seven single nucleotide polymorphisms (SNPs) in the MTR , MTRR , MTHFR , TYMS , ADH1C , ALDH2 , GSTP1 , NAT1 , NAT2 , CYP2E1 DRD2 , DRD3 , and SLC6A4 were genotyped. Five hundred and seventy patients with histopathogically confirmed breast cancer and 497 controls were included in the present study. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). Increased risk was observed for homozygotes at the MTR SNPs (rs1770449 and rs1050993) with the OR = 2.21 (95% CI 1.18–4.16) and OR = 2.24 (95% CI 1.19–4.22), respectively. A stratified analysis by menopausal status indicated the association between the NAT2 SNP (rs1799930) and breast cancer was mainly evident in premenopausal women (OR 2.70, 95% CI 1.20–6.07), while the MTRR SNP (rs162049) was significant in postmenopausal women (OR 1.61, 95% CI 1.07–2.44). Furthermore, SNPs of the genes that contribute to alcohol behavior, DRD3 (rs167770), DRD2 (rs10891556), and SLC6A4 (rs140701), were also associated with an increased risk of breast cancer. No gene–gene or gene–environment interactions were observed in this study. Our results suggest that genetic polymorphisms in folate and alcohol metabolic pathway influence the risk of breast cancer in Thai population.

BackgroundPancreatic cancer is considered a rare type of cancer, but the mortality rate is high. Cannabinoids extracted from the cannabis plant have been interested as an alternative treatment in cancer patients. Only a few studies are available on the antitumor effects of cannabinoids in pancreatic cancer. Therefore, this study aims to evaluate the antitumor effects of cannabinoids in pancreatic cancer xenografted mouse model.Materials and MethodsTwenty-five nude mice were subcutaneously transplanted with a human pancreatic ductal adenocarcinoma cell line (Capan-2). All mice were randomly assigned into 5 groups including negative control (gavage with sesame oil), positive control (5 mg/kg 5-fluorouracil intraperitoneal administration), and cannabinoids groups that daily received THC:CBD, 1:6 at 1, 5, or 10 mg/kg body weight for 30 days, respectively. Xenograft tumors and internal organs were collected for histopathological examination and immunohistochemistry.ResultsThe average tumor volume was increased in all groups with no significant difference. The average apoptotic cells and caspase-3 positive cells were significantly increased in cannabinoid groups compared with the negative control group. The expression score of proliferating cell nuclear antigen in positive control and cannabinoids groups was decreased compared with the negative control group.ConclusionsCannabinoids have an antitumor effect on the Capan-2-derived xenograft mouse model though induce apoptosis and inhibit proliferation of tumor cells in a dose-dependent manner.

Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process. Clonality study in HCC finds diverse evolution patterns. Linear HCC is less aggressive, with GTF2IRD2B driver mutations. Non-linear has shallow/deep branching patterns with frequent TP53 driver mutations.

DNA repair plays an important role in tumor development. The base excision repair (BER) pathway mainly removes DNA damage caused by ionizing radiation and reactive oxidative species. Here, we examined possible associations between polymorphisms in three important BER genes ( OGG1 Ser326Cys, APEX1 Asp148Glu, XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln) and breast cancer incidence in Thai women. The study population consisted of 507 breast cancer cases and 425 controls. Odds ratios (OR) were adjusted by multivariate logistic regression analysis for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education. For homozygous carriers of the Glu allele in APEX1 , a significant protective effect was found when compared to Asp/Asp carriers (odds ratio (OR) = 0.60, 95% confidence interval (CI) = 0.38–0.94). Subgroup analysis based on menopausal status revealed increased breast cancer risk in postmenopausal women and OGG1 (OR = 2.05, 95% CI 1.14–3.69). Reconstructed diplotypes for XRCC1 showed that CGA/CGA carriers had an increased risk of breast cancer compared with carriers of the wild type diplotype CGG/CGG (OR = 2.56, 95% CI 1.28–5.15). When the joint effects of XRCC1 , APEX1 and OGG1 polymorphisms were evaluated, individuals homozygous for two or three risk alleles were at increased risk (OR = 1.88, 95% CI 1.26–2.82). In conclusion, our data suggest that Thai women with a certain XRCC1 diplotype or homozygous for two or three variant alleles of XRCC1 , OGG1 , and APEX1 are likely to have an increased susceptibility to breast cancer.

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥ 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection.