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1.
Hered Cancer Clin Pract ; 19(1): 6, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419454

RESUMO

INTRODUCTION: The role of PALB2 in carcinogenesis remains to be clarified. Our main goal was to determine the prevalence of PALB2 (509_510delGA and 172_175delTTGT) mutations in bladder and kidney cancer patients from Polish population. MATERIALS AND METHODS: 1413 patients with bladder and 810 cases with kidney cancer and 4702 controls were genotyped for two PALB2 variants: 509_510delGA and 172_175delTTGT. RESULTS: Two mutations of PALB2 gene were detected in 5 of 1413 (0.35%) unselected bladder cases and in 10 of 4702 controls (odds ratio [OR], 1.7; 95% CI 0.56-4.88; p = 0.52). Among 810 unselected kidney cancer cases two PALB2 mutations were reported in two patients (0,24%) (odds ratio [OR], (OR = 1.2; 95% CI 0.25-5.13; p = 0.84). In cases with mutations in PALB2 gene cancer family history was negative. CONCLUSION: We found no difference in the prevalence of recurrent PALB2 mutations between cases and healthy controls. The mutations in PALB2 gene seem not to play a major role in bladder and kidney cancer development in Polish patients.

3.
Nat Genet ; 53(1): 65-75, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33398198

RESUMO

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33423179

RESUMO

PURPOSE: It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80. METHODS: Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk. RESULTS: Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk. CONCLUSIONS: Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.

5.
J Trace Elem Med Biol ; 64: 126682, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33249371

RESUMO

BACKGROUND: We assessed whether blood cadmium levels were associated with incident lung cancer and could be used in the context of a screening program for early-stage lung cancer. MATERIAL AND METHODS: We measured blood cadmium levels among 205 lung cancer patients and 205 matched controls. Cases and controls were matched for sex, age and smoking history (total pack-years, years since cessation for former smokers). RESULTS: The odds ratio for those in the highest quartile of cadmium level (versus lowest) was four-fold (OR = 4.41, 95 % CI:2.01-9.67, p < 0.01). The association was present in former smokers (OR = 16.8, 95 % CI:3.96-71.2, p < 0.01), but not in current smokers (OR = 1.23, 95 % CI: 0.34-4.38) or in never smokers (OR not defined). Among former smokers, the association was present in both early- and late-stage lung cancer. CONCLUSION: Blood cadmium levels may be a marker to help with the early detection of lung cancer among former smokers.

6.
Gynecol Oncol ; 159(3): 820-826, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33010967

RESUMO

OBJECTIVE: BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation. METHOD: Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures. RESULTS: A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37-0.58; P < 0.0001). CONCLUSIONS: These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.

7.
Cancers (Basel) ; 12(10)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992489

RESUMO

Familial clustering, twin concordance, and identification of high- and low-penetrance cancer predisposition variants support the idea that there are families that are at a high to moderate excess risk of cancer. To what extent there may be families that are protected from cancer is unknown. We wanted to test genetically whether cancer-free families share fewer breast, colorectal, and prostate cancer risk alleles than the population at large. We addressed this question by whole-genome sequencing (WGS) of 51 elderly cancer-free individuals whose numerous (ca. 1000) family members were found to be cancer-free ('cancer-free families', CFFs) based on face-to-face interviews. The average coverage of the 51 samples in the WGS was 42x. We compared cancer risk allele frequencies in cancer-free individuals with those in the general population available in public databases. The CFF members had fewer loss-of-function variants in suggested cancer predisposition genes compared to the ExAC data, and for high-risk cancer predisposition genes, no pathogenic variants were found in CFFs. For common low-penetrance breast, colorectal, and prostate cancer risk alleles, the results were not conclusive. The results suggest that, in line with twin and family studies, random environmental causes are so dominant that a clear demarcation of cancer-free populations using genetic data may not be feasible.

8.
Breast Cancer ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32888145

RESUMO

BACKGROUND: The objective of this study was to determine spectrum and prevalence of germline mutations in TP53 gene among Polish women with early-onset breast cancer (BC), which has not been determined until now. METHODS: A cohort of 100 females with BC diagnosed ≤ 30 years of age and with a positive family history of cancer was used as a discovery cohort. 1880 women with BC ≤ 45 years old and a control group of 2000 healthy women were genotyped as a replication phase of this study. RESULTS: Four heterozygous pathogenic missense mutations were detected in a group of 100 patients with early-onset breast cancer. On the basis of software prediction and available literature data, all these variants were defined as pathogenic. None of these TP53 variants were detected among 1880 breast cancer patients and 2000 healthy controls. No large mutations were found among early-onset cases using MLPA reaction. CONCLUSION: Germline pathogenic TP53 variants were found in 4% early-onset Polish BC patients. No founder mutations were identified in Polish population. To improve the treatment and surveillance screening, the search for germline TP53 pathogenic variants is recommended for all female BC cases diagnosed ≤ 30 years old.

9.
Nutrients ; 12(9)2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32948020

RESUMO

As mothers age, the risk of adverse pregnancy outcomes may increase, but the results so far are controversial and several issues remain unknown, such as the impact of maternal weight on the effects associated with older age. In a prospective cohort of 912 Polish women with singleton pregnancies (recruited in 2015-2016), we assessed the pregnancy outcomes depending on the mother's age (18-24, 25-29, 30-34, 35-39, and ≥40 years). Women aged ≥35 years (vs. <35 years) were assessed in terms of body mass index (BMI). Multidimensional logistic regression was used to calculate the odds ratios (with 95% confidence intervals) of the pregnancy results. The risk profiles (using the Lowess method) were applied to determine the threshold risk. We found that both the youngest and the oldest group members displayed higher adjusted odds ratios of preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth <37th week (U-shaped risk). In the remaining cases, the age ≥40 years, compared to the youngest age 18-24 years, was associated with a higher adjusted risk of gestational hypertension (GH) (AOR = 5.76, p = 0.034), gestational diabetes mellitus GDM-1 (AOR = 7.06, p = 0.016), cesarean section (AOR = 6.97, p <0.001), and low birth weight LBW (AOR = 15.73, p = 0.033) as well as macrosomia >4000 g (AOR = 8.95, p = 0.048). We found that older age ≥35 years (vs. <35 years) was associated with higher adjusted odds ratios of all the pregnancy outcomes investigated. In obese women, these adverse older age related results were found to be more intense in GH study, as well as (though weaker) in birth <37th week study, small-for-gestational age birth weight (SGA), LBW, large-for-gestational age birth weight (LGA), and macrosomia. In overweight women, these adverse older age related results were found to be more intense in preterm birth study, as well as (though weaker) in SGA and LBW. In underweight women, adverse pregnancy outcomes related to older age were more intense in a study of cesarean section. At the same time, underweight was associated with reversal of some negative effects of older age (we found lower odds ratios of GDM-1 diabetes). The maternal threshold age above which the risk of GH, PE, GDM, caesarean section, and preterm birth increased was 33-34 years (lower than the threshold of 35 years assumed in the literature), and the threshold risk of IUGR, LBW, SGA, LGA, and macrosomia was 36-37 years. Main conclusions: Older maternal age was associated with a higher chance of all kinds of obstetric complications. Older women should particularly avoid obesity and overweight.

10.
Int J Cancer ; 147(10): 2793-2800, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32875559

RESUMO

In designing national strategies for genetic testing, it is important to define the full spectrum of pathogenic mutations in prostate cancer (PCa) susceptibility genes. To investigate the frequency of mutations in PCa susceptibility genes in Polish familial PCa cases and to estimate gene-related PCa risks and probability of aggressive disease, we analyzed the coding regions of 14 genes by exome sequencing in 390 men with familial prostate cancer and 308 cancer-free controls. We compared the mutation frequencies between PCa cases and controls. We also compared clinical characteristics of prostate cancers between mutation carriers and noncarriers. Of the 390 PCa cases, 76 men (19.5%) carried a mutation in BRCA1, BRCA2, NBN, ATM, CHEK2, HOXB13, MSH2 or MSH6 genes. No mutations were found in BRIP1, PTEN, TP53, MLH1, PMS2 and SPOP. Significant associations with familial PCa risk were observed for CHEK2, NBN, ATM, and HOXB13. High-grade (Gleason 8-10) tumors were seen in 56% of BRCA2, NBN or ATM carriers, compared to 21% of patients who tested negative for mutations in these genes (OR = 4.7, 95% CI 2.0-10.7, P = .0003). In summary, approximately 20% of familial prostate cancer cases in Poland can be attributed to mutations in eight susceptibility genes. Carriers of mutations in BRCA2, NBN and ATM develop aggressive disease and may benefit from intensified screening and/or chemotherapy.

11.
Eur J Cancer Prev ; 29(6): 511-519, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32976206

RESUMO

Evaluation 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.

12.
Nutrients ; 12(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887442

RESUMO

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.

13.
Cancers (Basel) ; 12(8)2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32824581

RESUMO

There are twenty recurrent mutations in six breast-cancer-predisposing genes in Poland (BRCA1, BRCA2, CHEK2, PALB2, NBN, and RECQL). The frequencies of the twenty alleles have not been measured in a large series of early-onset breast cancer patients from Poland unselected for family history. We genotyped 2464 women with breast cancer diagnosed below age 41 years for twenty recurrent germline mutations in six genes, including BRCA1, BRCA2 CHEK2, PALB2, NBN, and RECQL. A mutation in one of the six genes was identified in 419 of the 2464 early-onset breast cancer cases (17%), including 22.4% of those cases diagnosed below age 31. The mutation frequency was 18.8% for familial breast cancer cases and 6% for non-familial cases. Among women with breast cancer below age 31, the mutation frequency was 23.6% for familial cases and 17.4% in non-familial cases. The majority of mutations (76.2%) were seen in BRCA1 and BRCA2. In Poland, a panel of twenty recurrent mutations in six genes can identify a genetic basis for a high percentage of early-onset cases and testing is recommended for all women with breast cancer at age 40 or below.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32765800

RESUMO

Background: Matrix metalloproteinases (MMPs) and metallothioneins (MTs) are Zinc-related proteins which are involved in processes crucial for carcinogenesis such as angiogenesis, proliferation and apoptosis. Several single nucleotide polymorphisms (SNPs) in MMPs and MTs that affect genes expression have been associated with cancer risk, including breast, lung and colon. Methods: The study group consisted of 648 unselected patients (299 with breast cancer, 199 with lung cancer, 150 with colon cancer) and 648 unaffected individuals. Five SNPs, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A were genotyped and serum zinc (Zn) level was measured. The cancer risk was calculated using multivariable logistic regression with respect to Zn. Results: None of the 5 tested polymorphisms showed a correlation with cancer risk in studied groups, although for MMP-2, MMP-7 and MT2A non-significant differences in genotypes frequencies among cases and controls were observed. Conclusions: Analyses of polymorphisms, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A in relation to serum Zn level did not show significant association with breast, lung and colon cancer risk among polish patients. Further studies are needed to verify this observation.

15.
Biol Trace Elem Res ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32648197

RESUMO

Lung cancer is the leading cause of cancer-related death worldwide. Exposure to environmental and occupational carcinogens is an important cause of lung cancer. One of these substances is chromium, which is found ubiquitously across the planet. The International Agency for Research on Cancer has classified chromium(VI) as a human carcinogen. The aim of this study was to assess whether serum chromium levels, as well as DNA variants in selected genes involved in carcinogenesis, xenobiotic-metabolism, and oxidative stress could be helpful in the detection of lung cancer. We conducted a study using 218 lung cancer patients and 218 matched healthy controls. We measured serum chromium levels and genotyped ten genetic variants in ERCC2, XRCC1, MT1B, GSTP1, ABCB1, NQ01, CRTC3, GPX1, SOD2 and CAT. The odds ratios of being diagnosed with lung cancer were calculated using conditional logistic regression with respect to serum chromium level and genotypes. The odds ratio for the occurrence of lung cancer increased with increasing serum chromium levels. The difference between the quartiles with the lowest vs. highest chromium level was more than fourfold in the entire group (OR 4.52, CI 2.17-9.42, p < 0.01). This correlation was significantly increased by more than twice when specific genotypes were taken into consideration (ERCC-rs12181 TT, OR 12.34, CI 1.17-130.01, p = 0.04; CRTC3-rs12915189 non GG, OR 9.73, CI 1.58-60.10, p = 0.01; GSTP1-rs1695 non AA, OR 9.47, CI 2.06-43.49, p = < 0.01; CAT-rs1001179 non CC, OR 9.18, CI 1.64-51.24, p = 0.01). Total serum chromium levels > 0.1 µg/L were correlated with 73% (52/71) of lung cancers diagnosed with stage I disease. Our findings support the role of chromium and the influence of key proteins on lung cancer burden in the general population.

16.
J Med Genet ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546565

RESUMO

PURPOSE: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. METHODS: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. RESULTS: The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. CONCLUSIONS: We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.

17.
Breast Cancer Res Treat ; 181(2): 423-434, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279280

RESUMO

BACKGROUND: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). METHODS: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope. RESULTS: The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula. CONCLUSIONS: Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.


Assuntos
Neoplasias da Mama/patologia , Tomada de Decisão Clínica , Segunda Neoplasia Primária/patologia , Medição de Risco/métodos , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Agências Internacionais , Mastectomia , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/cirurgia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Fatores de Risco
18.
Nutrients ; 12(4)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316207

RESUMO

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 (ß = -0.130; p = 0.002), and Fe (ß = -0.164; p < 0.0001), but positive associations with Cu (ß = 0.320; p < 0.000001). The relationships between Se and maternal age (ß = 0.167; p < 0.0001), Se and smoking (ß = -0.106; p = 0.011) and Cu, and gestational age from the 10-14th week (ß = 0.142; p < 0.001) were also found. Secondary education was associated with Zn (ß = 0.132; p = 0.004) and higher education was associated with Cu (ß = -0.102; p = 0.023). A higher financial status was associated with Fe (ß = 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.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32211398

RESUMO

Hodgkin lymphoma (HL) is a lymphoproliferative malignancy of B-cell origin that accounts for 10% of all lymphomas. Despite evidence suggesting strong familial clustering of HL, there is no clear understanding of the contribution of genes predisposing to HL. In this study, whole genome sequencing (WGS) was performed on 7 affected and 9 unaffected family members from three HL-prone families and variants were prioritized using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2). WGS identified a total of 98,564, 170,550, and 113,654 variants which were reduced by pedigree-based filtering to 18,158, 465, and 26,465 in families I, II, and III, respectively. In addition to variants affecting amino acid sequences, variants in promoters, enhancers, transcription factors binding sites, and microRNA seed sequences were identified from upstream, downstream, 5' and 3' untranslated regions. A panel of 565 cancer predisposing and other cancer-related genes and of 2,383 potential candidate HL genes were also screened in these families to aid further prioritization. Pathway analysis of segregating genes with Combined Annotation Dependent Depletion Tool (CADD) scores >20 was performed using Ingenuity Pathway Analysis software which implicated several candidate genes in pathways involved in B-cell activation and proliferation and in the network of "Cancer, Hematological disease and Immunological Disease." We used the FCVPPv2 for further in silico analyses and prioritized 45 coding and 79 non-coding variants from the three families. Further literature-based analysis allowed us to constrict this list to one rare germline variant each in families I and II and two in family III. Functional studies were conducted on the candidate from family I in a previous study, resulting in the identification and functional validation of a novel heterozygous missense variant in the tumor suppressor gene DICER1 as potential HL predisposition factor. We aim to identify the individual genes responsible for predisposition in the remaining two families and will functionally validate these in further studies.

20.
Nutrients ; 12(3)2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32213887

RESUMO

Excessive birth weight has serious perinatal consequences, and it "programs" long-term health. Mother's nutritional status can be an important element in fetal "programming"; microelements such as selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) are involved in many metabolic processes. However, there are no studies assessing the relationship of the microelements in the peri-conceptual period with the risk of excessive birth weight. We performed a nested case control study of serum microelements' levels in the 10-14th week of pregnancy and assessed the risk of large-for-gestational age (LGA) newborns using the data from a prospective cohort of pregnant women recruited in 2015-2016 in Poznan, Poland. Mothers delivering LGA newborns (n = 66) were examined with matched mothers delivering appropriate-for-gestational age (AGA) newborns (n = 264). Microelements' levels were quantified using mass spectrometry. The odds ratios of LGA (and 95% confidence intervals) were calculated by multivariate logistic regression. In the whole group, women with the lowest quartile of Se had a 3 times higher LGA risk compared with women in the highest Se quartile (AOR = 3.00; p = 0.013). Importantly, the result was sustained in the subgroup of women with the normal pre-pregnancy BMI (AOR = 4.79; p = 0.033) and in women with a male fetus (AOR = 6.28; p = 0.004), but it was not sustained in women with a female fetus. There were no statistical associations between Zn, Cu, and Fe levels and LGA. Our study provides some preliminary evidence for the relationships between lower serum Se levels in early pregnancy and a higher risk of large-for-gestational age birth weight. Appropriate Se intake in the periconceptual period may be important for optimal fetal growth.

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