Parents' Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease

The clinical advantages of the newborn screening programme (NBS) in the UK are well described in the literature. However, there has been little exploration of the psychosocial impact on the family. This study followed the principles of grounded theory to explore parents' experiences of receiving the initial positive NBS result for their child with cystic fibrosis (CF) or sickle cell disease (SCD). Semi-structured, qualitative interviews were conducted with 22 parents (12 mothers and 10 fathers) whose children had been diagnosed with CF or SCD via NBS and were under the age of 1 year at the time of interview. The main themes that arose from the data were; parents previous knowledge of the condition and the NBS programme, the method of delivery and parental reactions to the result, sharing the results with others, the impact on parental relationships and support strategies. Study conclusions indicate that most parents thought initial positive NBS results should be delivered by a health professional with condition specific knowledge, preferably with both parents present. Genetic counselling needs to include a focus on the impact of NBS results on parental relationships. Careful consideration needs to be given to strategies to support parents of babies who have positive NBS results both in terms of the psychological health and to assist them in sharing the diagnosis

Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States.

Peer reviewe

TNFRSF1B +676 T>G polymorphism predicts survival of non-Small cell lung cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in <it>TNF-α </it>and <it>TNFRSF1B </it>genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both <it>TNF-α </it>and <it>TNFRSF1B </it>and prognosis of NSCLC patients treated with chemoradiotherapy.</p> <p>Methods</p> <p>We genotyped five potentially functional polymorphisms of <it>TNF-α </it>and <it>TNFRSF1B </it>genes [<it>TNF-α </it>-308 G>A (rs1800629) and -1031 T>C (rs1799964); <it>TNFRSF1B </it>+676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).</p> <p>Results</p> <p>We found that the <it>TNFRSF1B </it>+676 GG genotype was associated with a significantly better OS of NSCLC (GG <it>vs. </it>TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG <it>vs. </it>GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the <it>TNFRSF1B </it>+676 GG was an independent prognosis predictor in this NSCLC cohort (GG <it>vs. </it>GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N_2-3<it>vs. </it>N_0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T_3-4<it>vs. </it>T_0-2: HR = 1.48, 95% CI = 1.08-2.03).</p> <p>Conclusions</p> <p>Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of <it>TNFRSF1B </it>+676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.</p

Incidence of hereditary non-polyposis colorectal cancer [HNPCC] in the city of Szczecin, north-western Poland

The study population consisted of 140 consecutive colorectal cancer patients, inhabitants of the city of Szczecin, north-west Poland, who were histopathologically diagnosed in the period of 2 years - 1991-1992. Family history was obtained in 124 (88.6%) of patients. A definitive diagnosis of HNPCC was established if requirements of the International Collaborative Group on HNPCC (ICG- HNPCC) were met. Suspected HNPCC were recognised according to criteria described by Ponz de Leon or Mecklin or Kunitomo. HNPCC as defined by International Collaborative Group on HNPCC was identified in 2 (1.6%) families. Suspected HNPCC were recognised in 16.9%, 3.2% and 4.0% of patients if Ponz de Leon or Mecklin or Kunitomo criteria were applied, respectively. In our series in 19 of 124 cases, colorectal carcinomas were diagnosed in patients under 50 years of age. Only in one of these cases, features characteristic of HNPCC other than young age were found which suggests that in our region the frequency of somatic or germ line de novo mutations in genes predisposing to colorectal cancer may be high. Our results suggest that the frequency of HNPCC inherited from ancestors in Poland and other countries is approximately similar and this syndrome is common disease everywhere

Increased constitutional chromosome sensitivity to bleomycin in patients with hereditary non-polyposis colorectal cancer [HNPCC]

It has been suggested that mutagen sensitivity is a constitutional factor which may be useful in identification of patients with an increased risk for the development of tumors. In this study, the chromosome sensitivity to bleomycin was measured according to Hsu in patients with hereditary non-polyposis colorectal cancer (HNPCC), sporadic colorectal cancer and in control persons with no tumor history in family. In vitro lymphocytes were exposed to bleomycin according to Hsu and chromosomal damage was quantified by scoring breaks of 100 cells. A significant difference (P < 0.01) in the mean number of breaks per cell (b/c) was found between HNPCC patients (0.59 ± 0.14; n = 12; mean age 55.4 yrs) and control individuals (0.35 ± 0.13: n = 12; mean age 55.8 yrs). In contrast, patients with sporadic colorectal cancer showed a mean b/c value of 0.43 ± 0.14 (n = 14; mean age 63.4 yrs) which was not significantly higher than that in control individuals for this group (0.42 ± 0.15; n = 14; mean age 63.1 yrs). Selenium protected lymphocytes of HNPCC patients against bleomycin activity in vitro