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"Lubinski, Jan"
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Serum selenium levels and the risk of progression of laryngeal cancer
by
Mojsiewicz, Magdalena
,
Muszynska, Magdalena
,
Kaczmarek, Katarzyna
in
Adult
,
Aged
,
Aged, 80 and over
2018
Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival has not been evaluated.
We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry.
The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 μg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile. The corresponding multivariate HR was 3.07 (95% CI 1.59 to 5.94).
This study suggests that a selenium level in excess of 70 μg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis.
Journal Article
Serum Selenium Level in Early Healthy Pregnancy as a Risk Marker of Pregnancy Induced Hypertension
by
Sajdak, Stefan
,
Lewandowska, Małgorzata
,
Lubiński, Jan
in
Adult
,
antioxidants
,
Biomarkers - blood
2019
Selenium (Se) is an antioxidant nutrient whose deficiency can influence adverse outcomes of pregnancy. The aim of this study is to determine whether serum Se level in early healthy pregnancy may be a risk marker for pregnancy induced hypertension. We obtained data from our prospective study in which we recruited healthy women in weeks 10–14 of a single pregnancy. In this analysis, we examined 121 women who subsequently developed pregnancy-induced hypertension and matched 363 women who remained normotensive. We measured Se levels (using the ICP-MS technique) in the serum in weeks 10–14 of the pregnancy. The odds ratios of pregnancy-induced hypertension (95% confidence intervals) were calculated using multivariate logistic regression. We found that the mean Se level was lower in the case group compared to the control (57.51 vs. 62.89 μg/L; p = 2.6 × 10−10). Excessive body mass index (BMI) and smoking influenced the estimated odds ratios. In the subgroup of women who had never smoked with normal pre-pregnancy BMI, the adjusted odds ratio (AOR) of pregnancy-induced hypertension was 15.34 (95% CI: 2.73–86.31, p = 0.002) for Se levels in the lowest quartile (≤57.68 µg/L), as compared to the highest quartile (>66.60 µg/L), after adjusting for all the accepted confounders. In the whole cohort, the prognostic value of Se by logistic regression showed that the area under curve (AUC) = 0.814. In our study, one can consider the role of Se as a risk marker of pregnancy-induced hypertension.
Journal Article
The Role of Early Pregnancy Maternal Selenium Levels on the Risk for Small-for-Gestational Age Newborns
2019
It has not yet been established, whether or not the maternal serum selenium (Se) in early pregnancy may be a risk marker of small-for-gestational age (SGA) birth weight. Selenium is important for human health and is involved in oxidative balance, a key element in the development of the placenta and fetus. This innovative study was nested in a prospective cohort of 750 women recruited in the 10-14th week of a single pregnancy, all of whom were healthy during recruitment. We examined mothers delivering SGA infants (with birth weight <10th percentile) (
= 48) and matched mothers delivering appropriate-for-gestational age (AGA) infants (between 10-90th percentile) (
= 192). We measured the maternal microelement concentrations in the serum from the 10-14th gestational week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of SGA (and 95% confidence intervals) were assessed in logistic regression. The mean maternal Se concentrations were lower in mothers in the SGA group compared to the AGA group (59.60 vs. 62.54 µg/L;
= 0.020). Women in the lowest Q
quartile of Se (≤56.60 µg/L) have about three times higher risk of SGA compared to women in the higher quartiles (Q
or Q
); the odds ratio of SGA was OR = 3.02 (
= 0.019) for Q
vs. Q
quartile. The risk profile graph confirms the results. We found that excessive pre-pregnancy BMI (body mass index) affected the estimated SGA odds ratios. Early pregnancy maternal serum selenium status can be a risk marker of SGA newborns and more research is needed in larger groups.
Journal Article
Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial
by
Fodde, Riccardo
,
Movahedi, Mohammad
,
Moeslein, Gabriela
in
Adenoma - prevention & control
,
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
,
aspirin
2011
Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo.
In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990.
861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95% CI 0·35–1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95% CI 0·32–0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19–0·86, p=0·02) and an IRR of 0·37 (0·18–0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups.
600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment.
European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma.
Journal Article
First Trimester Microelements and Their Relationships with Pregnancy Outcomes and Complications
by
Sajdak, Stefan
,
Więckowska, Barbara
,
Lewandowska, Małgorzata
in
birth weight
,
blood serum
,
Body Mass Index
2020
Microelements involved in the oxidative balance have a significant impact on human health, but their role in pregnancy are poorly studied. We examined the relationships between first trimester levels of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu), as well as maternal characteristics and pregnancy results. The data came from a Polish prospective cohort of women in a single pregnancy without chronic diseases. A group of 563 women who had a complete set of data, including serum microelements in the 10–14th week was examined, and the following were found: 47 deliveries <37th week; 48 cases of birth weight <10th and 64 newborns >90th percentile; 13 intrauterine growth restriction (IUGR) cases; 105 gestational hypertension (GH) and 15 preeclampsia (PE) cases; and 110 gestational diabetes mellitus (GDM) cases. The microelements were quantified using mass spectrometry. The average concentrations (and ranges) of the elements were as follows: Se: 60.75 µg/L (40.91–125.54); Zn: 618.50 µg/L (394.04–3238.90); Cu: 1735.91 µg/L (883.61–3956.76); and Fe: 1018.33 µg/L (217.55–2806.24). In the multivariate logistic regression, we found that an increase in Se of 1 µg/L reduces the risk of GH by 6% (AOR = 0.94; p = 0.004), the risk of IUGR by 11% (AOR = 0.89; p = 0.013), and the risk of birth <34th week by 7% (but close to the significance) (AOR = 0.93; p = 0.061). An increase in Fe of 100 µg/L reduces the risk of PE by 27% (AOR = 0.73; p = 0.009). In the multivariable linear regression, we found negative strong associations between prepregnancy BMI, Se (β = −0.130; p = 0.002), and Fe (β = −0.164; p < 0.0001), but positive associations with Cu (β = 0.320; p < 0.000001). The relationships between Se and maternal age (β = 0.167; p < 0.0001), Se and smoking (β = −0.106; p = 0.011) and Cu, and gestational age from the 10–14th week (β = 0.142; p < 0.001) were also found. Secondary education was associated with Zn (β = 0.132; p = 0.004) and higher education was associated with Cu (β = −0.102; p = 0.023). A higher financial status was associated with Fe (β = 0.195; p = 0.005). Other relationships were statistically insignificant. Further research is needed to clarify relationships between first trimester microelements and pregnancy complications. In addition, attention should be paid to lifestyle-related and socioeconomic factors that affect microelement levels.
Journal Article
First Trimester Serum Copper or Zinc Levels, and Risk of Pregnancy-Induced Hypertension
2019
Early identification of women at risk of developing pregnancy-induced hypertension (PIH) is very important. The involvement of copper (Cu) and zinc (Zn) in the oxidative balance suggests the possibility of their association with this disease, in which oxidative stress plays a key role. However, it has not been established so far whether the microelement levels in early pregnancy may be risk markers of the disease, as prospective studies are limited in number. In our innovative single-center study, we identified from a prospective cohort of healthy women in the 10–14th week of a single pregnancy: women subsequently developing pregnancy-induced hypertension (n = 121) and matched women remaining normotensive (n = 363). We measured the concentrations of microelements in the serum from 10–14 week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of the disease (and 95% confidence intervals) were assessed in logistic regression. In the whole cohort, the odds ratio (OR) of PIH was 1.52 (p = 0.174) for women in the lowest (Q1) quartile of Cu (≤1540.58 µg/L) compared with women in the highest (Q4) quartile (>1937.46 µg/L), but adjusted odds ratio (AOR) was 2.17 (p = 0.019) after adjusted for pre-pregnancy body mass index (BMI) and gestational age at recruitment. The higher levels of Cu in the subgroup of BMI ≥ 25 kg/m2 compared to normal BMI were found (1847.64 vs. 1673.36 µg/L; p < 0.0001). In the subgroup of women with the normal pre-pregnancy BMI, the adjusted odds ratio of PIH was AOR = 2.95 (p = 0.040) for Q1 vs. Q4 quartile. Our results suggest that lower Cu levels in early pregnancy may be connected with higher risk of PIH, but BMI affected estimated odds ratios. Zinc levels had no effect on the risk.
Journal Article
Correction: Serum selenium levels and the risk of progression of laryngeal cancer
by
Mojsiewicz, Magdalena
,
Muszynska, Magdalena
,
Lubiński, Jakub
in
Health risks
,
Laryngeal cancer
,
Selenium
2018
[This corrects the article DOI: 10.1371/journal.pone.0184873.].
Journal Article
Pre-Pregnancy Obesity vs. Other Risk Factors in Probability Models of Preeclampsia and Gestational Hypertension
2020
In the face of the obesity epidemic around the world, attention should be focused on the role of maternal obesity in the development of pregnancy. The purpose of this analysis was to evaluate the prediction of preeclampsia (PE) and isolated gestational hypertension (GH) for a number of maternal factors, in order to investigate the importance of pre-pregnancy obesity (body mass index, BMI ≥ 30 kg/m2), compared to other risk factors (e.g., prior PE, pregnancy weight gain (GWG), infertility treatment, interpregnancy interval, family history, the lack of vitamin supplementation, urogenital infection, and socioeconomic factors). In total, 912 women without chronic diseases were examined in a Polish prospective cohort of women with a single pregnancy (recruited in 2015–2016). Separate analyses were performed for the women who developed GH (n = 113) vs. 775 women who remained normotensive, as well as for those who developed PE (n = 24) vs. 775 controls. The probability of each disease was assessed for the base prediction model (age + primiparity) and for the model extended by one (test) variable, using logistic regression. Three measures were used to assess the prediction: area under curve (AUC) of the base and extended model, integrated discrimination improvement (IDI) (the index shows the difference between the value of the mean change in the predicted probability between the group of sick and healthy women when a new factor is added to the model), and net reclassification improvement (NRI) (the index focuses on the reclassification table describing the number of women in whom an upward or downward shift in the disease probability value occurred after a new factor had been added, including results for healthy and sick women). In the GH prediction, AUC increased most strongly when we added BMI (kg/m2) as a continuous variable (AUC = 0.716, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.068, p < 0.001). The addition of BMI as a continuous variable or BMI ≥ 25 kg/m2 improved the classification for healthy and sick women the most (NRI = 0.571, p < 0.001). In the PE prediction, AUC increased most strongly when we added BMI categories (AUC = 0.726, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.050, p = 0.080). The addition of BMI categories improved the classification for healthy and sick women the most (NRI = 0.688; p = 0.001). After summing up the results of three indexes, the probability of hypertension in pregnancy was most strongly improved by BMI, including BMI ≥ 25 kg/m2 for the GH prediction, and BMI ≥ 30 kg/m2 for the PE prediction. Main conclusions: Pre-pregnancy BMI was the most likely factor to increase the probability of developing hypertension in pregnancy, compared to other risk factors. Hierarchies of PE and GH risk factors may suggest different (or common) mechanisms of their development.
Journal Article
Can Serum Iron Concentrations in Early Healthy Pregnancy Be Risk Marker of Pregnancy-Induced Hypertension?
2019
The aim of this study was to assess the relationship between serum iron concentrations in early healthy pregnancy and the risk of pregnancy-induced hypertension. The data comes from our prospective cohort study in which we recruited healthy women in week 10–14 of single pregnancy. We examined a study group (n = 121) consisting of women subsequently developing pregnancy-induced hypertension and a control group (n = 363) of matched women remaining normotensive. We measured iron concentrations in the serum collected in 10–14 gestational week, using the ICP-MS technique (mass spectrometry with inductively coupled plasma). The odds ratios of the disease (95% confidence intervals) for iron concentrations were assessed in multivariate logistic regression. We found that the mean microelement concentration was lower in the case group compared to normotensive controls (p = 0.011). Women in the lowest quartile of iron (≤801.20 µg/L) had a 2.19-fold increase in pregnancy-induced hypertension risk compared with women in the highest quartile (>1211.75 µg/L) (odds ratio (OR) = 2.19; 95% CI: 1.24–3.88; p = 0.007). This result was sustained after adjusted for all the accepted confounders. Women in the higher Q2 quartile (801.20–982.33 µg/L) had a 17% lower risk, compared with those in the highest quartile (OR = 0.83; 95% CI: 0.65–2.32; p = 0.519).
Journal Article
PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy
by
Gugala, Karol
,
Lubinski, Jan
,
Domagala, Pawel
in
Biological and medical sciences
,
Biomarkers, Tumor - genetics
,
BRCA1 Protein - biosynthesis
2011
Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including
BRCA1
-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130
BRCA1
-associated and 594
BRCA1
-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in
BRCA1
-associated versus
BRCA1
-non-associated carcinomas in all tumors (
P
< 0.0001), in the basal-like group (
P
= 0.0086), TN (
P
= 0.0015), and non-basal-like groups (
P
= 0.016) but not in the non-TN group. Among
BRCA1
-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among
BRCA1
-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with
BRCA1
status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.
Journal Article