Common variants of DNA repair genes and malignant melanoma.

In the current study, we evaluated the possible associations of seven common variants of the DNA repair and cell cycle control genes BRCA2 and CHEK2 with malignant melanoma (MM). We genotyped 630 unselected MM patients and over 3700 controls (newborns, age- and sex-matched healthy adults with negative cancer family histories, and the adults selected at random by family doctors) for the prevalence of three common variants of the BRCA2 (T1915M, N991D and N372H) and four common variants of the CHEK2 (1100delC, VS2+1G --> A, I157T and del5395). Our study strongly suggests that the common variant of the BRCA2 gene -- the N991D variant is associated with malignant melanoma risk (OR=1.8, p=0.002 after Bonferroni correction). Patients homozygote for the N991D variant were present in 0.32% of cases and only 0.13% of controls. The other variants studied were not over-represented among MM patients when compared to the general population. In conclusion, we report an increased melanoma risk among carriers of the N991D change of the BRCA2 and no association of the CHEK2 changes with malignant melanoma.

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.

XPD common variants and their association with melanoma and breast cancer risk.

There are suggestions in the literature that common variants in the XPD gene may be associated with an altered risk of melanoma and breast cancer. To establish if the XPD common variants Asp312Asn and Lys751Gln are associated with an increased melanoma or breast cancer risk we performed an association study based on genotyping 426 unselected patients with malignant melanoma (MM) and 1830 consecutive breast cancer cases and compared the results to 1262 geographically matched newborns, 621 adults from the region of Szczecin (unselected for age and cancer family history), 421 healthy adults age- and sex-matched with the melanoma cases and 511 healthy controls matched with the breast cancer patients from the region of Szczecin. Additionally we examined the prevalence of three additional XPD variants, Gly156Gly, Leu485Pro and Arg112His amongst the 421 unselected melanoma patients. All of the variants when evaluated singularly were found not to be associated either with melanoma or breast cancer risk in younger or older patients. A modest association was observed with breast cancer risk when the Lys751Gln_CC/Asp312Asn_AA genotype (OR=1.5, p<0.05) segregated together. Individuals harboring the Lys751Gln_CC/Gly156Gly_CC genotype were significantly over-represented among late-onset melanoma cases (OR=1.7, p<0.05). The results of analyses of linkage disequilibrium and haplotype frequency support the thesis that a combination of at least two SNPs (Lys751Gln_CC/Gly156Gly_CC or Lys751Gln_CC/Asp312Asn_AA) inherited as a haplotype was associated with disease. These two pairs of SNPs could therefore be regarded as a single hereditary unit that would have a very small probability of being disrupted by recombination. Additional studies are required to determine whether these particular changes can be associated with an increased risk of other malignancies at different sites of origin.

NOD2 variants and the risk of malignant melanoma.

Both hereditary and environmental factors are important in the aetiology of malignant melanoma. Among the risk factors for malignant melanoma are immunodeficiency and immunosuppression. The recently identified NOD2 gene is involved in the regulation of immune function through activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Three common NOD2 mutations -- 3020insC, G908R and R702W -- have been shown to be associated with chronic inflammatory disease such as Crohn's disease, the 3020insC also with human malignancy colorectal cancer. We examined the frequency of the NOD2 variants in 424 patients with malignant melanoma and 649 controls. The 3020insC mutation was present in 6.9% of unselected cases and 7% of the controls (odds ratio (OR) 1.0; P not significant). The mutation was present in 6.8% of 162 cases diagnosed under the age of 50 and in 7.1% of cases diagnosed after the age of 50. A mutation was present in the index case in 5% of 40 familial melanomas (OR 0.7; P not significant). There were no statistically significant differences between prevalence of G908R and R702W in malignant melanoma patients and controls. In conclusion, the three common NOD2 mutations are not associated with increased risk of development of malignant melanoma.

Increased risk of breast cancer in relatives of malignant melanoma patients from families with strong cancer familial aggregation.

The aim of this study was to evaluate the risk of occurrence of malignancies of different site of origin in patients with malignant melanoma (MM) of the skin and their first-degree relatives from families with cancer familial aggregations with unknown pathogenetic background (CFA). We analysed tumour spectrum and age at diagnosis of malignancies in 51 families with MM/CFA. In addition, we evaluated observed frequency (OF); expected frequency (EF); and relative risk (RR) of occurrence of malignancies in these families. In all cases peripheral blood examination of common Polish founder BRCA1 mutations was performed. In 25 families, we analysed loss of heterozygosity of BRCA1 and BRCA2 genes. We identified two subgroups of cases: 22 MM/CFA families with MM diagnosed before 55 years (< or =55 MM/CFA) and 29 MM/CFA families with MM diagnosed after 55 (>55 MM/CFA). In these families we observed increased proportion of breast cancers: 17.52% in the first subgroup (mean age of diagnosis 48.5) and 12.15% in the second subgroup. The odds ratio for breast tumours occurring before 50 in < or =55 MM/CFA families was 3.71. We also observed increased numbers of liver cancers, CSU and leukaemias. OF and EF analyses revealed increased risk of occurrence of cancers of breast (OF 10.4%, EF 4.5%) and liver (OF 1.9%, EF 0.8%) in women from MM/CFA families, RR for breast tumours was approximately 3.3 in < or =55 MM/CFA families. Molecular examination of MM/CFA families revealed no alterations within the BRCA2 gene and one germline mutation of the BRCA1 gene. In conclusion, it seems to be justified to consider systematic breast surveillance beginning at the age around 35-40 years as an option in women from < or =55 MM/CFA families.

Fetal and placental power Doppler imaging in normal and high-risk pregnancy.

OBJECTIVE: Computer analysis of organ power Doppler (PD) imaging has recently become available. The aim of the study was to evaluate gestational trends in placenta-, fetal lung-, liver- and kidney-blood flow in normal pregnancies and relate it to signals in high-risk pregnancies. METHODS: PD signals were recorded in normal singleton pregnancies between 26 and 42 weeks of gestation. Signals were also recorded in 63 high-risk pregnancies. Fixed preinstalled PD system installations for each organ were used during examinations. Images from PD scan were recorded on video tape and off-line analysed by computer. Mean flow signal intensity was calculated for each organ. Umbilical and uterine artery Doppler velocimetry were also recorded in high-risk pregnancies. RESULTS: PD signals from the four organs indicated increasing organ blood flow until approximately 34 weeks of gestation, from where the organ signals seemed to decrease. High-risk pregnancies seemed to have lower PD signal intensity, which was more pronounced in cases with signs of placental vascular resistance. CONCLUSION: The results suggest that a decrease in fetal organ blood flow might indicate a centralisation of fetal circulation in normal pregnancy at term, as a physiological response to a decrease in placental perfusion. In the high-risk pregnancies the placental and fetal organ blood flow seem to be even further reduced, suggesting a more intense centralisation of circulation.

[The use of color Doppler ultrasonography in the diagnosis of benign breast tumors]. / Zastosowanie techniki koloroweo Dopplera w diagnostyce Lagodnych schorzen gruczolu sutkowego.

The paper describes Color Doppler Velocity (CDV) technique with clinical implications in examinations of patients with benign breast lesions. Results suggest that CDV might be useful in differentiation of the breast lesions in routine clinical work.

[Meigs syndrome--diagnostic difficulties]. / Zespól meigsa--trudnosci diagnostyczne.

Meigs' syndrome in 68 years woman with pleural effusion and ovarian tumour was described. The cause of the pleural liquid in Meigs' syndrome is still not clear. New views on the pathogenesis and diagnostic methods of pleural liquids causes were presented.

[Evaluation of using the B-mode color system in sonomammography with computer analysis of images compared with conventional gray scale modalities]. / Ocena zastosowania systemu B-mode color w sonomammografii wraz z komputerowa analiza obrazów uzyskiwanych w tym systemie w porównaniu z konwencjonalna skala szarosci.

The paper describes B-mode color and B-tag modalities with clinical implications in breast examinations. New color techniques show increased sensitivity of the human eye to color pictures compared to gray scale levels. Computer analysis of pictures obtained in color mode and gray scale supports these findings.

[Major risk factors for endometrial carcinoma]. / Glówne czynniki ryzyka w raku trzonu macicy.

Our results were compared with the results from numerous recent studies concerning important risk factors for the endometrial carcinoma. We revealed that only age more then 50 with conjunction with obesity is the important risk factor. We didn't proved the protection role of the pregnancy emphasized in the literature. The role of others epidemiologic risk factors for the endometrial carcinoma remains still unequivocally explained.

[A rare case of appendicitis in pregnancy]. / Rzadki przypadek zapalenia wyrostka robaczkowego w ciazy.

It has been described a case of appendicitis in atypical appendix localisation complicated by perforation with coexisting pleuropneumonia on the right side in 21 year old primipara in 33 week of gestation. It has been performed cesarean section with simultaneous surgical intervention.

[Role of laparoscopy in diagnosis and therapy of pain syndromes of the small pelvis in women]. / Rola laparoskopii w diagnostyce i terapii zespolów bólowych miednicy malej u kobiet.

An analysis was done of 36 female patients with chronic pain in the small pelvis, not regressing after long-term treatment with antibiotics on an outpatient basis. During laparoscopic examination the following was diagnosed: post-inflammatory changes in 61.3%, varicosity of the parametrium in 11.0%, ovarian cysts, ovarian polycystic degeneration, foci of endometriosis, and postoperative adhesions were diagnosed in an equal per cent of 5.5%. During laparoscopy 21 operations were carried out. The obtained results prove that laparoscopy is a valuable diagnostic and therapeutic method.