Overabundant FANCD2, alone and combined with NQO1, is a sensitive marker of adverse prognosis in breast cancer.

BACKGROUND: Defective DNA repair is central to the progression and treatment of breast cancer. Immunohistochemically detected DNA repair markers may be good candidates for novel prognostic and predictive factors that could guide the selection of individualized treatment strategies. PATIENTS AND METHODS: We have analyzed nuclear immunohistochemical staining of BRCA1, FANCD2, RAD51, XPF, and PAR in relation to clinicopathological and survival data among 1240 paraffin-embedded breast tumors, and additional gene expression microarray data from 76 tumors. The antioxidant enzyme NQO1 was analyzed as a potential modifier of prognostic DNA repair markers. RESULTS: RAD51 [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.70-0.94, P = 0.0050] and FANCD2 expression (HR 1.50, 95% CI 1.28-1.76, P = 1.50 × 10(-7)) were associated with breast cancer survival. High FANCD2 expression correlated with markers of adverse prognosis but remained independently prognostic in multivariate analysis (HR 1.27, 95% CI 1.08-1.49, P = 0.0043). The FANCD2-associated survival effect was most pronounced in hormone receptor positive, HER2-negative tumors, and in tumors with above-median NQO1 expression. In the NQO1-high subset, patients belonging to the highest quartile of FANCD2 immunohistochemical scores had a threefold increased risk of metastasis or death (HR 3.10, 95% CI 1.96-4.92). Global gene expression analysis indicated that FANCD protein overabundance is associated with the upregulation of proliferation-related genes and a downregulated nucleotide excision repair pathway. CONCLUSION: FANCD2 immunohistochemistry is a sensitive, independent prognostic factor in breast cancer, particularly when standard markers indicate relatively favorable prognosis. Taken together, our results suggest that the prognostic effect is linked to proliferation, DNA damage, and oxidative stress; simultaneous detection of FANCD2 and NQO1 provides additional prognostic value.

cagA, vacA and iceA virulence genes of Helicobacter pylori isolates of children in Finland.

cagA, vacA s and m genotypes and iceA alleles were analyzed from Helicobacter pylori strains isolated from 17 Finnish children and 32 children of non-Finnish origin living in Finland. Twelve children in the latter group were eastern European and 15 were of African origin. Only three children of non-Finnish origin were born in Finland. The vacA sla subtype was more prevalent in the isolates from Finnish children than African children (76% vs. 7%, P<0.001); vacA s1b frequencies were 5% and 67%, respectively (P<0.001). The iceA1 allele was significantly more prevalent in African than Finnish isolates (93% vs. 35%, P< 0.01). Considerable variation was noted in the frequency of vacA s1 subtypes and iceA alleles in children originating from different geographic regions, but the geographic variation of s1 subtypes resembled that described in other reports.

The relationship between irritable bowel syndrome and psychiatric illness. A family study.

Although irritable bowel syndrome (IBS) is a common disorder among gastrointestinal clinic outpatients, it continues to be a diagnosis of exclusion. In treatment-seeking populations, IBS has been frequently associated with psychiatric illness, and this co-occurrence has added to controversy about the validity of the IBS diagnosis. This study is a preliminary effort to examine the nature of this relationship by using the family study design. The probands consisted of 20 patients with IBS and 20 patients who had undergone laproscopic cholecystectomy. Their first-degree relatives were interviewed to obtain lifetime diagnoses of functional gastrointestinal and psychiatric syndromes. Significantly more IBS probands had lifetime psychiatric illness than the cholecystectomy probands. The lifetime prevalence of IBS as well as other functional gastrointestinal syndromes was not significantly different between the groups of relatives. However, significantly more relatives of the IBS probands had lifetime psychiatric illness than the relatives of the cholecystectomy probands. Among the relatives with functional gastrointestinal disorders, significantly more had psychiatric illness. This preliminary study provides support for a relationship between IBS and psychiatric illness by the finding of an increased prevalence of psychiatric disorders among the relatives of patients who have IBS.