The most prevalent type of cancer among males is prostate cancer. Survival is considered quite good, but it can be further improved when risk factors are optimized. One of these factors is ...micronutrients, including Se and Zn. To our knowledge, the interaction between Se and Zn and prostate cancer remains undescribed. This study aimed to investigate the optimal levels of selenium (Se) and zinc (Zn) and their impact on the survival of individuals diagnosed with prostate cancer. A total of 338 prostate cancer patients were enrolled in this study, which was conducted in Poland between 2009 and 2015. Mass spectrometry, which uses inductively coupled plasma mass, was used to assess serum element levels before treatment. The study participants were categorized into quartiles (QI-QIV) based on the distributions of Se and Zn levels observed among surviving participants. Cox regression was used to assess the association between serum Se and Zn levels and the survival of prostate cancer patients. Our results reveal the effect of combined Se and Zn levels on survival in prostate cancer patients (SeQI-ZnQI vs. SeQIV-ZnQIV; HR = 20.9). These results need further research to establish Se/Zn norms for different populations.
There is emerging interest in the relationship between several serum micronutrients and the prognosis of patients with breast cancer. The relationship between serum zinc and copper levels and breast ...cancer prognosis is unclear. In our study, we included 583 patients with breast cancer diagnosed between 2008 and 2015 in the region of Szczecin, Poland. In a blood sample obtained before treatment, serum zinc and copper levels were quantified by mass spectroscopy. Each patient was assigned to one of four categories (quartiles) based on the distribution of the elements in the entire cohort. Patients were followed from diagnosis to death over a mean of 10.0 years. The 10-year overall survival was 58.3% for women in the highest and 82.1% for those in the lowest quartile of serum copper/zinc ratio (
< 0.001). The multivariate hazard ratio (HR) for breast cancer death was 2.07 (95% CI 1.17-3.63;
= 0.01) for patients in the highest quartile of serum copper/zinc ratio compared to those in the lowest. There is evidence that the serum zinc level and copper/zinc ratio provide an independent predictive value for overall survival and breast cancer-specific survival after breast cancer diagnosis.
In a prospective study, we measured the associations between three serum elements (Se, Zn and Cu) and the prognosis of 1475 patients with four different types of cancer (breast, prostate, lung and ...larynx) from University Hospitals in Szczecin, Poland. The elements were measured in serum taken after diagnosis and prior to treatment. Patients were followed from the date of diagnosis until death from any cause or until the last follow-up date (mean years of follow-up: 6.0-9.8 years, according to site). Kaplan-Meier curves were constructed for all cancers combined and for each cancer separately. Age-adjusted hazard ratios (HRs) were estimated using Cox regression. The outcome was all-cause mortality. A Se level in the highest quartile was also associated with a reduced mortality (HR = 0.66; 95%CI 0.49-0.88;
= 0.005) in all-cause mortality for all cancers combined. Zn level in the highest quartile was also associated with reduced mortality (HR = 0.55; 95%CI 0.41-0.75;
= 0.0001). In contrast, a Cu level in the highest quartile was associated with an increase in mortality (HR = 1.91; 95%CI 1.56-2.08;
= 0.0001). Three serum elements-selenium, zinc and copper-are associated with the prognosis of different types of cancer.
The association of BRCA1/2 mutations with melanoma is not completely determined; the interpretation of variants of unknown significance is also problematic. To evaluate these issues we explored the ...molecular basis of melanoma risk by performing whole-exome sequencing on a cohort of 96 unrelated Polish early-onset melanoma patients and targeted sequencing of BRCA1/2 genes on additional 30 melanoma patients with familial aggregation of breast and other cancers. Sequencing was performed on peripheral blood. We evaluated MutationTaster, Polyphen2, SIFT, PROVEAN algorithms, analyzed segregation with cancer disease (in both families with identified BRCA2 variants) and in one family performed LOH (based on 2 primary tumors). We found neither pathogenic mutations nor variants of unknown significance within BRCA1. We identified two BRCA2 variants of unknown significance: c.9334G>A and c.4534 C>T. Disease allele frequency was evaluated by genotyping of 1230 consecutive melanoma cases, 5000 breast cancer patients, 3500 prostate cancers and 9900 controls. Both variants were found to be absent among unselected cancer patients and healthy controls. The MutationTaster, Polyphen2 and SIFT algorithms indicate that c.9334G>A is a damaging variant. Due to lack of tumour tissue LOH analysis could not be performed for this variant. The variant segregated with the disease. The c.4534 C>T variant did not segregate with disease, there was no LOH of the variant. The c.9334G>A variant, classified as a rare variant of unknown significance, on current evidence may predisposes to cancers of the breast, prostate and melanoma. Functional studies to describe how the DNA change affects the protein function and a large multi-center study to evaluate its penetrance are required.
The effects of heavy metals on cancer risk have been widely studied in recent decades, but there is limited data on the effects of these elements on cancer survival. In this research, we examined ...whether blood concentrations of the heavy metals arsenic, cadmium, mercury and lead were associated with the overall survival of lung cancer patients. The study group consisted of 336 patients with lung cancer who were prospectively observed. Blood concentrations of heavy metals were measured to study the relationship between their levels and overall survival using Cox proportional hazards analysis. The hazard ratio of death from all causes was 0.99 (p = 0.94) for arsenic, 1.37 (p = 0.15) for cadmium, 1.55 (p = 0.04) for mercury, and 1.18 (p = 0.47) for lead in patients from the lowest concentration quartile, compared with those in the highest quartile. Among the patients with stage IA disease, this relationship was statistically significant (HR = 7.36; p < 0.01) for cadmium levels in the highest quartile (>1.97–7.77 µg/L) compared to quartile I (0.23–0.57 µg/L, reference). This study revealed that low blood cadmium levels <1.47 µg/L are probably associated with improved overall survival in treated patients with stage IA disease.
Understanding of the etiology and pathogenesis of pancreatic cancer (PaCa) is still insufficient. This study evaluated the associations between concentrations of selenium (Se) and copper (Cu) in the ...serum of PaCa patients.
The study included 100 PaCa patients and 100 control subjects from the same geographical region in Poland. To determine the average concentration of Se, Cu, and ratio Cu:Se in the Polish population, assay for Se and Cu was performed in 480 healthy individuals. Serum levels of Se and Cu were measured using inductively coupled plasma mass spectrometry.
In the control group, the average Se level was 76 µg/L and Cu 1,098 µg/L. The average Se level among PaCa patients was 60 µg/L and the mean Cu level was 1,432 µg/L. The threshold point at which any decrease in Se concentration was associated with PaCa was 67.45 µg/L. The threshold point of Cu level above which there was an increase in the prevalence of PaCa was 1,214.58 µg/L. In addition, a positive relationship was observed between increasing survival time and Se plasma level.
This retrospective study suggests that low levels of Se and high levels of Cu might influence development of PaCa and that higher levels of Se are associated with longer survival in patients with PaCa. The results suggest that determining the level of Se and Cu could be incorporated into a risk stratification scheme for the selection and surveillance control examination to complement existing screening and diagnostic procedures.
There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the ...presence of colorectal cancer. The blood copper level was measured among 187 colorectal cancer patients and 187 matched controls. Cases and controls were matched for sex, smoking status (yes/no) and year of birth. Among the cases, the mean blood copper level was 1031 µg/L (range 657 µg/L to 2043 µg/L) and among the controls, the mean blood copper level was 864 µg/L (range 589 µg/L to 1433 µg/L). The odds ratio for colorectal cancer for those in the highest quartile of copper level (versus the lowest) was 12.7 (95% CI: 4.98–32.3; p < 0.001). Of the patients with stage I–II colon cancer, 62% had a copper level in the highest quartile. A blood copper level in excess of 930 µg/L is associated with an increase in the prevalence of colorectal cancer in the Polish population and its potential use in early detection programs should be considered.
Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic ...loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968A, rs8034191G) and 5p15 (rs402710T) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p ≤ 0.0001, 0.0005, 0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findings on lung cancer but fails to show association of SNPs located in 15q25.1 and 5p15 region with other smoking related cancers like bladder and laryngeal cancer.
An important group of breast cancers is those associated with inherited susceptibility. In women, several predisposing mutations in genes involved in DNA repair have been discovered. Women with a ...germline pathogenic variant in BRCA1 have a lifetime cancer risk of 70%. As part of a larger prospective study on heavy metals, our aim was to investigate if blood arsenic levels are associated with breast cancer risk among women with inherited BRCA1 mutations. A total of 1084 participants with pathogenic variants in BRCA1 were enrolled in this study. Subjects were followed from 2011 to 2020 (mean follow-up time: 3.75 years). During that time, 90 cancers were diagnosed, including 67 breast and 10 ovarian cancers. The group was stratified into two categories (lower and higher blood As levels), divided at the median (<0.85 µg/L and ≥0.85 µg/L) As level among all unaffected participants. Cox proportional hazards models were used to model the association between As levels and cancer incidence. A high blood As level (≥0.85 µg/L) was associated with a significantly increased risk of developing breast cancer (HR = 2.05; 95%CI: 1.18–3.56; p = 0.01) and of any cancer (HR = 1.73; 95%CI: 1.09–2.74; p = 0.02). These findings suggest a possible role of environmental arsenic in the development of cancers among women with germline pathogenic variants in BRCA1.
Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among PaCa patients and ...assessed their possible association with the risk of disease in Poland. In the study 383 PaCa patients and 4,000 control subjects were genotyped for founder mutations in: BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1 (657del5) and PALB2 (509_510delGA, 172_175delTTGT). A statistically significant association between the 657del5 mutation and an increased risk of pancreatic cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA) was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000 (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509_510delGA and 172_175delTTGT mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8 (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000 (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1 (657del5) was associated with an increased risk of PaCa in heterozygous carriers, indicating that this mutation appears to predispose to cancer of the pancreas. By identifying pancreatic cancer risk groups, founder mutation testing in Poland should be considered for people at risk for PaCa.
What's new?
The genetic and molecular mechanisms that lead to pancreatic cancer are still poorly understood. In this study, the authors examined founder mutations that are known to be associated with several types of cancer in Poland. They found that a particular mutation in NBS1 was associated with a significant increase in the risk of pancreatic cancer. Screening for this mutation may therefore help identify people who are at risk for pancreatic cancer in Poland and probably other Slavic populations.
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