Jan Lubinski

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..3% of individuals) and may be responsible for an important fraction of cancer cases. We estimate that the lifetime cancer risk among carriers of this allele is 30% higher than that of individuals with two wild-type alleles...

..Markers associated with majority of groups included: BRCA1, CHEK2, p53, TNRnTT, FGFRnAA, XPD CC/AA and XPD GG. Some markers appeared to be group specific and included polymorphisms in CDKN2A, CYP1B1, M3K nAA, and RS67...

..It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland...

..To investigate whether or not a genetic variant in BARD1 (Cys557Ser) contributes to early-onset breast cancer in Poland, or modifies the risk of breast cancer in women with an inherited predisposition to breast cancer...

..We are presenting it on examples of late-onset breast cancers from Poland, but it seems to be justified to expect that similar results can be achieved from other malignancies...

..The PHB 1630 C/T single nucleotide polymorphism was associated with breast cancers with clinical features typical for BRCA1-positive tumours and is deserving of further study...

..5; p < 0.0001). We conclude that the I157T variant of CHEK2 increases the risk of colorectal cancer among MMR-negative, HNPCC/HNPCC-related families in Poland...

..The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations...

..In conclusion, the RAD51 C allele seems to protect against both breast and ovarian cancer in women harboring BRCA1 mutations...

..0 years vs. 64.0) and the difference was significant (P = 0.05). This study suggests that BRCA1 mutations may be associated with early-onset of colorectal cancer...

..1-11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9-51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation...

..The results of this study revealed a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma...

..Two-gene models provide numerous challenges for gene identification and cancer risk assessment...

..It is important that other studies of CHEK2 mutation carriers be conducted to confirm this hypothesis...

..5; p = 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population...

..Together, it appears that functional polymorphisms in the MTHFR gene modify the risk of breast and may potentially alter the risk of ovarian cancer in women with an inherited predisposition...

..It appears that the 657del5 mutation in exon 6 of the NBS1 gene is responsible for the occurrence of a small but significant proportion of familial breast cancer patients...

..03). These data suggest that the BRCA2 T1915M polymorphism alone might be associated with a reduced risk of breast cancer, but among CHEK2 mutation carriers, it may lead to an unexpectedly high risk...

..To investigate the contribution of CDKN2A A148T common variant to early-onset breast cancer in Poland, and to establish the characteristic features of these cancers...

..Although the carcinogenic mechanism associated with this particular locus of 8q24 is unclear it appears to be specific to prostate cancer...

..Familial laryngeal cancer may not be a single site-specific cancer syndrome...

..The CYP1B1 gene is a polymorphic member of the P450 gene family and is considered to be a candidate gene for cancers of various types...

..Moreover, the G446A polymorphism is not significantly more frequent in CFA cases except for families in which the proband had melanoma. To confirm this result more cases of melanoma should be analysed...

..Breast cancer risk did not differ between carriers of the 300 T > G and 5382insC mutation. Our results suggest that the PHB 3'UTR T allele increases the risk of breast cancer in patients who are already at increased risk of disease...

..Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility...

..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...

..Thus, it appears that these polymorphisms do not influence disease risk in Polish women carrying one of the three common BRCA1 founder mutations...

..The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T...

..76), but significant associations were observed between the presence of the allele and early-onset breast cancer (OR = 1.9; p = 0.01) and between the allele and ductal breast cancer with an in situ component (OR = 2.2; p = 0.006)...

..This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers...

..This is one of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of all breast cancers in Poland can be attributed to one of three protein-truncating mutations in CHEK2...

..8 [95% confidence interval (CI) = 1.2-2.9; P = 0.01]. These observations support the hypothesis that early radiation exposure may be a risk factor for breast cancer in BRCA1 carriers...

..To assess retinal function in HNPCC gene mutation carriers...

..It is expected that the penetrance of BRCA2 mutations for stomach cancer will vary from country to country, reflecting local environmental and lifestyle factors...

..We concluded that cystadenoma is likely to be a characteristic feature of the subgroup of families with hereditary ovarian cancers unassociated with BRCA1/BRCA2 constitutional mutations...

..6; p > 0.0001). This is the first report to demonstrate that different mutations of the same gene may be associated with specific histologic subtypes of cancer...

..In conclusion, it appears that the 3020insC mutation of the NOD2/CARD15 gene may be a genetic predisposing factor for aggregations of breast and lung cancer...

..07-0.62; P = 0.0015). This finding suggests that RAD51 is a genetic modifier of breast cancer risk in BRCA1 carriers in the Polish population. It will be of interest to confirm this in other populations as well...

..A molecular basis was identified (the CYP1B1 355T/T genotype) in only 2 of the 8 early cases suggestive of there being additional, as yet unknown genes that are associated with an early-onset laryngeal-breast cancer phenotype...

..Among 14 families without BRCA1 Polish founder mutations in this gene were excluded in 2 families and BRCA2 mutation was excluded in one family...

..We found this model of genetic testing and delivery of genetic information to be very efficient in a population in which founder mutations predominate. There is a need for similar studies in other populations...

..To evaluate whether this CHK2 founder mutation is associated with MM in patients with LFS syndrome, more MM cases from LFS families should be examined...

..Our results provide evidence that the two truncating mutations of CHEK2 confer a moderate risk of prostate cancer in Polish men and that the missense change appears to confer a modest risk...

..63, 95% CI, 0.48-0.83), and a potential effect on ovarian cancer risk (OR(adj) 0.62, 95% CI, 0.33-1.18; OR(clustered) 0.62, 95% CI, 0.47-0.83). Thus, the 936_C>T polymorphism appears to modify disease risks in BRCA1 carriers...

..A CHEK2 mutation (all variants combined) was found in 10.6% of the cancer cases and in 5.9% of the controls (OR = 1.9; 95%CI 1.3-2.7; p = 0.0003). We conclude that CHEK2 mutations increase the risk of bladder cancer in the population...

..g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke. We speculate that lung cancer cells with impaired CHEK2 function undergo increased rates of cell death...

..Our results suggest that the range of cancers associated with the rs6983267 marker might be larger than previously thought...

..We investigated whether or not inherited variation in MSR1, RNASEL and E-cadherin contribute to prostate cancer risk in Poland...

..BRCA1 carriers with late age of menarche, lower parity and long-term breast-feeding were less likely to develop breast cancer. Oral contraceptives protected against ovarian cancer...

..For a deleterious variant, one would expect a greater allele frequency in breast cancer cases than in ethnic-matched controls. In contrast, neutral polymorphic variants should be equally frequent in the two groups...

..83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65)...

..To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers...

..To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer...

..This rapid test will facilitate large-scale national epidemiologic and clinical studies of hereditary breast cancer, potentially including studies of chemoprevention...

..We found no strong association between MMP1 variation and the risk of MM or breast cancer. The finding of this study indicates an influence of MMP8 gene variation on melanoma susceptibility...

..The results revealed a paucity of mutations in CDKN2A/ARF, suggesting that in the Polish population this gene does not contribute significantly to either FMM or MM within the context of CFA...

..To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen...

..New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization...

..Additional studies are required to confirm whether this particular change is associated with increased risk of other nonmelanoma malignancies...

..The aim of this study was to analyze the occurrence of clinical features characteristic of breast cancer type 1 susceptibility protein (BRCA-1)-dependent tumors in a series of BRCA-1 mutation carriers with laryngeal cancer...

..89-1.32). The polymorphism was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers. The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers...

..0; P = 0.03) compared to families of other ethnic origins. In conclusion, both the position of mutation and the ethnic background of the family appear to contribute to the phenotypic variation observed in families with BRCA2 mutations...

..These results suggest that the combined iPLEX/TaqMan test is an outstanding tool for identification of recurrent mutations among hereditary colorectal cancer patients...

..Our results and reports by others indicate that, besides colorectal and endometrial cancer, the late-onset endometrioid type of ovarian cancer can be a feature of families with MSH6 germline mutations...

..It is important that mutation surveys be conducted in other countries prior to the introduction of national genetic screening programs...

..It has also been suggested that BRCA1 mutation is involved given the fact that BRCA1 mutation carriers are at increased risk for pancreatic cancer. However, a role of this mutation is not fully understood...

..Our findings suggest that healthcare providers should consider including a brief pretest psychological assessment before initiating genetic testing for BRCA1 and BRCA2...

..DHPLC was confirmed to be highly sensitive, specific and a cost-effective technique with particularly high potential for the detection of MSH2 and MLH1 gene mutations in the diagnostic setting...

..These findings need confirmation by more extensive studies because only a limited number of cases were analysed and there are relatively few reports published...

..To describe a Polish population with nonalcoholic fatty liver disease (NAFLD) with regard to HFE gene mutations, as well as analyzing demographic and clinical data...

..It is genetic disorder of iron metabolism, leading to iron accumulation and increased liver fibrosis. The association between alcoholic liver disease (ALD) and HFE gene mutations remains unclear and requires clarification...

..We were able to obtain blood samples from 19 of mutation positive cases. Eight (42%) of these harboured germline mutations in persons from distinct undiagnosed VHL families...

..The association between interleukin-1 polymorphisms, H. pylori and increased gastric cancer risk remains controversial...

..23; P = 0.0046). The results indicate that NOD2 may be a predisposing factor to colorectal cancer characterized by an older average age of disease onset in persons who do not harbor any other genetic predisposition to disease...

..Our analysis shows that testing of 4153delA, 5382insC, C61G BRCA1 mutations should be extremely effective and inexpensive tool in testing Lithuanian population aimed to identify individuals with high risk of breast and ovarian cancers...

..In the present study, an association of MDR1 gene polymorphism and the occurrence of colon cancer were evaluated...

..We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls...

..A common missense variant of the CDKN2A gene (A148T) predisposes to malignant melanoma in Poland. An association between malignant melanoma and breast cancer has been reported in several families with CDKN2A mutations,..

..The results of this study suggest that germ-line BRCA2 mutations account for rather small proportion of male breast cancer in Poland...

..Our findings suggest that constitutively active ERK1/2 kinases contribute to the growth of melanoma cells by negative regulation of the p27/Kip1 inhibitor...