FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Common variations in ERCC2 are associated with response to cisplatin chemotherapy and clinical outcome in osteosarcoma patients.

Platinum agents cause DNA cross-linking. Nucleotide excision repair genes play a key role in DNA damage repair. This study aims to investigate whether polymorphisms in these genes are associated with tumor response and survival in cisplatin-treated osteosarcoma patients. Eight single nucleotide polymorphisms in ERCC2, XPC, XPA, ERCC1, ERCC4 and ERCC5 genes were analyzed in 91 patients diagnosed with osteosarcoma and treated with cisplatin. A significant association with tumor response, after correction for multiple testing, was found for the Lys751Gln polymorphism in the ERCC2 gene. We found that only 45% of patients with at least one polymorphic G allele responded compared with 80% of patients homozygous for the common T allele (odds ratio=4.9, 95% confidence interval=1.64-14.54, adjusted P-value=0.047). In addition, carrying at least one ERCC2 Lys751GlnG allele was significantly associated with shorter event-free survival (median=184 months, compared with 240 months for TT homozygotes; hazard ratio=5.76, 95% confidence interval=1.30-25.55; P-value=0.021). Although ototoxicity was only recorded in 32 patients, we found weak evidence of an association with the CC genotype of XPC Lys939Gln (P-value= 0.042). This is the first pharmacogenetic study focused on osteosarcoma treatment providing evidence that polymorphic variants in DNA repair genes could be useful predictors of response to cisplatin chemotherapy in osteosarcoma patients.

Choleretic effect and intestinal propulsion of 'mate' (Ilex paraguariensis) and its substitutes or adulterants.

'Mate' or 'Yerba mate' (Ilex paraguariensis, Aquifoliaceae) is a tonic and stimulant beverage widely used in South America. It is also traditionally used in gastrointestinal disorders as eupeptic and choleretic agent. Accordingly, the effect of decoctions of the leaves of I. paraguariensis and three of its substitutes or adulterants (Ilex brevicuspis, Ilex argentina and Ilex theezans) on bile flow (BF) and intestinal propulsion were investigated. I. paraguariensis and I. brevicuspis induced an increase in BF, while the latter also enhanced intestinal transit. In contrast, neither I. argentina nor I. theezans exerted any effect on BF or intestinal propulsion. These results suggest that the therapeutic properties of I. paraguariensis will be affected when at least an adulterant is present in the final commercial product of Yerba mate.

[Epidemiologic study of an outbreak of echovirus type-9 meningitis]. / Estudio epidemiológico de un brote de meningitis por echovirus tipo-9.

BACKGROUND: Several agents are able to produce lymphocytic meningitis, but sometimes it's not possible their identification. The viruses are the etiological agents more frequently found, especially enteroviruses, mumps virus and herpes simplex virus, with different epidemiological patterns depending on time and geographic location. Most of the infections caused by enteroviruses are asymptomatics. In general the viral meningitis have a good prognostic with an acute benign course and serious signs of neurological affectation are infrequent. From 1991 it has been observed an increase of nonpolio enteroviral meningitis outbreaks in our Country. Echovirus-4 was isolated in most of the outbreaks notified during that year. Echovirus-9 was not isolated in any of them. METHODS: We describe the epidemiological and clinical characteristics of a lymphocytic meningitis outbreak that took place from June to July of 1993 in Burgos. RESULTS: Forty-eight patients, most of them children, were hospitalized with fever, headache, vomits and stiff neck with an increase in the total cell count in cerebospinal fluid (CSF). Echovirus-9 was isolated from fecal samples in eight patients. CONCLUSIONS: The etiology was attributed to Echovirus-9 because of microbiologic and epidemiologic findings. The incubation period can fluctuate between four an five days and fecal-oral transmission is the most probable mechanism.