Katarzyna Durda

A Low Selenium Level Is Associated with Lung and Laryngeal Cancers

Purpose It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls. Methods We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype. Results Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers. Conclusion A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.

Can selenium levels act as a marker of colorectal cancer risk

BackgroundSelenium has attracted attention because of its antioxidant properties. Antioxidants protects cells from damage. Certain breakdown products of selenium are believed to prevent tumor growth by enhancing the immune cell activity and suppressing the development of tumor blood vessels. In this observational study, selenium level was measured in a series of patients from Poland and Estonia to determine a correlation between levels of this microelement and colorectal cancer risk.MethodsA total of 169 colorectal cancer patients and 169 healthy controls were enrolled in the study after obtaining their informed consent. Selenium level in the blood serum was measured using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). The statistical analysis was performed by Fisher’s exact test.ResultsThe threshold point of selenium level was 55 μg/l and 65 μg/l for Poland and Estonia respectively, for an increase in cancer risk. The lower levels of selenium were associated with greater risk of colorectal cancer.ConclusionsThe result reveals a significant strong association between low selenium level and the colorectal cancer risk in both Estonian and Polish populations.

Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

Purpose This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs) and to poly(ADP-ribose) polymerase (PARP) inhibitors. Methods Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Results Thirty five (22.2%) of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7%) of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%), and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%). In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined) were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined) were identified in the hereditary non-triple-negative group. Conclusions Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

Arsenic (As) and breast cancer risk

The study was conducted to determine the correlations between serum concentration of arsenic (As) with increased or decreased predisposition to breast and ovarian cancer.

Selenium and the risk of cancer in BRCA1 carriers

It has not been established if dietary factors or nutritional supplements impact on the incidence of cancer in high-risk women. We randomised 1135 women with a BRCA1 mutation to 250 micrograms daily of elemental selenium as sodium selenite, or to placebo, in a double-blind trial. After a median follow-up period of 35 months (range 6 to 62 months), there were 60 incident cases of cancer diagnosed in the selenium-supplemented group, versus 45 cases in the placebo group (hazard ratio 1.4; 95% CI: 0.9 to 2.0). Selenium supplementation was not associated with a reduction in the risk of primary breast cancer (hazard ratio 1.3; 95% CI: 0.7 to 2.5), of contralateral breast cancer (hazard ratio 1.5; 95% CI: 0.7 to 3.2), or of ovarian cancer (hazard ratio 1.3; 95% CI: 0.6 to 2.7). The results of this study do not support the recommendation that selenium supplementation should be offered to BRCA1 carriers for chemoprevention. Part II Adnexectomy, genotypes and selenium level as markers of the risk of cancer In these part we conducted a nested case-control study of 68 women with breast cancer and 17 women with ovarian cancer and 170 controls matched 1 to 2. Cases and controls were matched for age at enrolment, past history of breast cancer, oophorectomy and whether they received selenium supplement or placebo during cancer chemoprevention trial. Combinations of clinical status, genotypes and selenium levels strongly associated with extremely low risk of cancer have been identified. The strongest associations have been found for GPX4 variants: a. all nTT and Se level 60-80µg/l – OR 0.32, p: 0.0009 b. all TT and Se level >80µg/l – OR 0.10, p: 0.047 c. for carriers without adnexectomy and with TT variant, Se level >80µg/l – OR 0.038, p: 0.014.

CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland

Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome characterized by a high risk of diffuse stomach cancer and lobular breast cancer. HDGC is caused by germline mutations in the CDH1 gene encoding the E-cadherin which is a member of the transmembrane glycoprotein family responsible for calcium-dependent, cell-to-cell adhesion and plays a fundamental role in the maintenance of cell differentiation and the normal architecture of epithelial tissues. Mutations in the CDH1 gene are detected in 30–46% of families that fulfil strong clinical criteria for HDGC and in about 11% of families fulfilling the modified criteria. In the present study, we investigated germline mutations in the CDH1 gene in Polish patients with HDGC. The entire coding sequence of CDH1 gene was analyzed by sequencing in 86 Polish cancer patients from families fulfilling the modified criteria of HDGC. We found several silent mutations including one common variant (c.2076T>C) present in 56 patients, and three rare variants (c.2253C>T, c.1896C>T, c.2634C>T) detected in 2 patients. In addition, we found four rare sequence variants of unknown significance localized in introns. We did not detect any deleterious mutations of the CDH1 gene. CDH1 gene mutations are not present in Polish families with HDGC defined by the modified clinical criteria. Further studies of families with HDGC matching the restrictive criteria for HDGC are needed.

Selenium as marker for cancer risk and prevention.

MARCIN LENER1*, KATARZYNA JAWORSKA1,3*, MAGDALENA MUSZYnSKA1,2, GRZEGORZ SUKIENNICKI1,2, KATARZYNA DURDA1, SATISH GUPTA1,3, ELŻBIETA ZŁOWOCKA-PERŁOWSKA1, JoZEF KŁADNY4, ANNA WIECHOWSKA-KOZŁOWSKA5, TOMASZ GRODZKI6, EWA JAWOROWSKA7, JAKUB LUBInSKI7, BARBARA GoRECKA-SZYLD8, GRAŻYNA WILK8, MIECZYSŁAW SULIKOWSKI9, TOMASZ HUZARSKI1, TOMASZ BYRSKI1, CEZARY CYBULSKI1, JACEK GRONWALD1, TADEUSZ DeBNIAK1, OLGIERD ASHURYK1, ALEKSANDRA TOŁOCZKO-GRABAREK1, ANNA JAKUBOWSKA1, ANTONI MORAWSKI10, JAN LUBInSKI1,2

Prospective observation of breast/ovarian cancer risk in BRCA1 carriers depending on serum selenium level optimized with diet

The aim of the study is to observe prospectively the possibility of lowering the cancer risk among BRCA1 carriers by optimizing selenium concentration in diet/organism. Results of studies performed in several centres, particularly of our own search, are strongly indicating on potential of decreasing breast/ovarian cancer risk among carriers by optimization of selenium concentration in the body. Studies will be performed on group of 1500 BRCA1 carriers. Cohort will be recruited during the first 6 months of the project. Mean length of follow-up will be 3 yrs. From all females serum will be collected for selenium analyses-at the beginning and, then, every 6 months. Participants will receive the list of products with selenium concentration estimated according to literature data and, additionally, information about e-store (http://www.dietaantyrakowa.pl) specialized in distribution of food products with defined amount of selenium. Information on optimal selenium concentration according to existing data will be provided also. It is expected that among ~750 carriers following recommended diet changes 38 cancers will be diagnosed and among the others ~750-60. The difference between groups will be statistically significant with p=0.0278. If necessary, investigation will be extended.

Selenium and the risk of cancer of the lung and larynx. A case-control study from a region with low selenium

Selenium deficiency has been suggested by several studies to be associated with cancer risk. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 86 cases of lung cancer, 87 cases of laryngeal cancer and an equal number of healthy controls. We studied the serum level of selenium and genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15) and the odds of being diagnosed with lung or laryngeal cancer. Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.7 µg/l for their matched controls (p 80 µg/l) was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.24 (95% CI 0.10 to 0.59; p = 0.002) for laryngeal cancer. In four selenoproteins studied here we found a modest associations of genetic variants in GPX1 and GPX4 with lung and TXNRD2 with laryngeal cancer risk. In this region of endemic low selenium level, there is a strong inverse association between the level of serum selenium and the risks of lung and laryngeal cancer.

Serum folate concentration and the incidence of lung cancer

Background Lung cancer is a leading cause of cancer-related mortality globally. Folate helps to maintain DNA integrity and to regulate gene expression. Serum folate levels may affect the risk of several cancers, including lung cancer. In this study we evaluated the association between serum folate concentration and variations in genes involved in folate metabolism with lung cancer incidence in Poland. Methods The study included 366 lung cancer patients and 366 control subjects. We measured serum folate concentration and genotyped six variants in MTHFR, MTR and MTRR genes. The odds ratios of being diagnosed with lung cancer were calculated using conditional univariable and multivariable logistic regression with respect to folate level and genotypes. Results The mean serum folate level was lower in lung cancer cases than in control group (20.07 nmol/l vs. 22.52 nmol/l, p = 0.002). The odds ratio for lung cancer declined with increasing serum content of the folate. The folate concentration of >25.71 nmol/l (IVth quartile) in comparison to <15.92 nmol/l (Ist quartile) was associated with an odds ratio of 0.61 (95%CI 0.40–0.95, p = 0.03). The analysis of variations in MTHFR, MTR and MTRR genes did not reveal any significant difference between lung cancer cases and controls in univariable and multivariable analyses. Conclusion In this case-control study, lower serum folate concentrations were associated with a higher risk of lung cancer diagnosis. Although previous findings have been somewhat mixed, our results add to the evidence that circulating folate levels may be an indicator of lung cancer risk.