The impact of oophorectomy on survival after breast cancer in BRCA1-positive breast cancer patients.

The aim of the study is to identify treatments which predict survival for women with a BRCA1 mutation, including oophorectomy and chemotherapy. 476 women with stage I to stage III breast cancer who carried a BRCA1 mutation were followed from diagnosis until April 2015. Information on treatment was obtained from chart review and patient questionnaires. Dates of death were obtained from the Poland vital statistics registry. Survival curves were compared for different subgroups according to treatment received. Predictors of overall survival were determined using the Cox proportional hazards model. The ten-year overall survival was 78.3 % (95 % CI 74.2-82.6 %) and the ten-year breast cancer-specific survival was 84.2 % (95 % CI 80.5-88.0 %). Sixty-two patients died of breast cancer, 14 patients died of ovarian cancer, and 2 patients died of peritoneal cancer. Oophorectomy was associated with a significant reduction in all-cause mortality in the entire cohort (adjusted HR = 0.41; 95 % CI 0.24-0.69; p = 0.0008) and in breast cancer-specific mortality among ER-negative breast cancer patients (HR = 0.44; 95 % CI 0.22-0.89; p = 0.02). Among women with breast cancer and a BRCA1 mutation, survival is greatly improved by oophorectomy due to the prevention of deaths from both breast and ovarian cancer.

CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors.

OBJECTIVE: Three founder alleles of the CHEK2 gene have been associated with predisposition to a range of cancer types in Poland. Two founder alleles (1100delC and IVS2 + 1G >A) result in a truncated CHEK2 protein and the other is a missense substitution, leading to the replacement of a threonine with an isoleucine (I157T). METHODS: To establish if these variants play a role in the etiology of ovarian tumors, we genotyped 1108 Polish women with various types of ovarian tumors and 4000 controls for the three CHEK2 variants. We included 539 Polish women with benign ovarian cystadenomas, 122 women with borderline ovarian malignancies and 447 women with invasive ovarian cancer. RESULTS: Positive associations were seen with the CHEK2 I157T missense variant and ovarian cystadenomas (OR = 1.7; P = 0.005), with borderline ovarian cancers (OR = 2.6; P = 0.002) and with low-grade invasive cancers (OR = 2.1; P = 0.04). There was no association with ovarian cancer of high grade (OR = 1.0). The association between the I157T missense variant was then confirmed in a second sample of Russian patients with borderline ovarian cancers (OR = 2.7; P = 0.06). CONCLUSION: These data indicate that CHEK2 variants may predispose to a range of ovarian tumor types of low malignant potential, but not to aggressive cancers.

BRCA1-positive breast cancers in young women from Poland.

We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.

Single Nucleotide Polymorphisms in exon 3 of the adiponectin gene in subjects with type 2 diabetes mellitus.

PURPOSE: Adiponectin (APM1)--a newly discovered adipocytokine secreted by fat tissue--was recently suggested to play a role in the genetic predisposition to type 2 diabetes, obesity and insulin resistance. Adiponectin gene is localized on chromosome 3q27 within the region which was identified as susceptibility locus for type 2 diabetes and metabolic syndrome. Till now genetic associations of two SNP in exon 2 (+45T/G) and intron 2 (+276G/T) of adiponectin gene with type 2 diabetes and adiponectin level were reported in Japanese population and with insulin resistance in some Caucasian populations (Italy, Germany). Moreover, in the proximal promoter region of the APM1 gene: SNP-11426A/G and -11391A/-11377G haplotype predicted the associations with fasting plasma glucose, type 2 diabetes and adiponectin levels. On the other hand the role of mutations in exon 3 of the adiponectin gene is not so well studied. MATERIAL AND METHODS: The aim of our study was the screening for rare mutation in exon 3 of adiponectin gene in the Polish subjects with type 2 diabetes as there is no data available about the frequency and role of these mutations in our population. The study was performed in the group of 187 Polish origin patients with type 2 diabetes (32 female and 155 male, mean age 54.1 +/- 8.6 yrs) and 102 age and sex matched healthy controls. RESULTS: The frequency of adiponectin gene mutations in exon 3 was 3.9%, while in the control group 0.98% and this difference was not statistically significant. We also observed that adiponectin level is significantly lower in patients with c.331 T-->C mutation (Y111H) in comparison to subjects without this mutation (5.0 ug/ml vs 14.4 ug/ml, p=0.0148). CONCLUSIONS: To our knowledge the present study is the first which shows that in Polish populations.

Relationship between gastroesophageal reflux disease and myocardial ischemia. Effect of reflux on temporary activity of autonomic nervous system.

PURPOSE: Assessment of the gastroesophageal reflux disease (GERD) influence on myocardial ischemia and autonomic nervous system (ANS) activity. MATERIAL AND METHODS: In 50 patients with angiographically confirmed ischemic heart disease (IHD) in I-III CCS class, simultaneous 24-hour ECG and esophageal pH-metry monitoring was performed. We assessed: (1) GERD occurrence in patients with IHD, (2) influence of pathological reflux (PR) on myocardial ischemia--number and total duration of ST depression episodes in GERD and non-GERD patients, (3) temporary activity of ANS was determined according to the dynamics of spectral HRV (Heart Rate Variability) analysis components (LF, HF, VLF, LF/HF). RESULTS: 23 patients (46%) fullfilled the GERD criteria. Patients with GERD had significantly higher number of ST depression episodes (4.13 vs 2.85, p = 0.013) as well as longer total duration of ischemia (64.73 vs 35.2 min, p = 0.034). Spectral HRV analysis showed the significant decrease of LF/HF ratio (p < 0.035), which indicates the sympathovagal balance shift towards the parasympathetic system caused by PR. CONCLUSIONS: 1. GERD is frequent condition in patients with angiographically confirmed IHD. Coexistence of GERD may predispose to the myocardial ischemia. 2. Gastroesophageal reflux may cause the shift of sympathovagal balance towards its parasympathetic component. This mechanism may induce esophago-cardiac reflex, leading to diminished myocardial perfusion.

[Alpha fetoproteins in serum of a patients with Hodgkin's disease]. / Alfa-fetoproteina w surowicy chorego z ziarnica zlosliwa.

Presence of alfa-fetoprotein was found in serum of patient in whom primary hepatoma was suspected. The post-mortem microscopical examination did not confirm the clinical diagnosis ut showed changes typical for Hodgkin's disease.