13 research outputs found
Association of some rare haplotypes and genotype combinations in the MDR1 gene with childhood acute lymphoblastic leukaemia.
To investigate their possible roles in disease susceptibility and some disease
characteristics we genotyped C3435T and G2677T/A polymorphisms in multidrug
resistance-1 (MDR1) gene with a single base extension method and the G34A and
C421A polymorphisms of the breast cancer resistance protein gene with an allelic
discrimination system in 396 children with acute lymphoblastic leukaemia (ALL)
and 192 control patients. While the distribution of individual alleles and
genotypes did not differ between patients and controls, there were significant
differences in the frequencies of some rare haplotypes and genotype combinations
in the MDR1 gene between the two groups
MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease
Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease. To evaluate the contribution of germline MSH6 mutations to early-onset colorectal cancer, we have analysed peripheral blood of 38 patients diagnosed with this disease before 45 years of age and who presented no family history of hereditary nonpolyposis colorectal cancer-related cancers. Blood samples from 108 healthy volunteers were analysed for those genetic alterations suspected to affect the function of MSH6. Of the seven (18.4%) MSH6 alterations found, we have identified three novel germline mutations, one 8 bp deletion leading to a truncated protein and two missense mutations resulting in the substitution of amino acids belonging to different polarity groups. High-frequency microsatellite instability was found in the patient with the MSH6 deletion, but not in the other 27 carcinomas analysed. No MLH1 promoter methylation was detected in tumour tissue. Our findings suggest that germline MSH6 mutations contribute to a subset of early-onset colorectal cancer. Further studies are warranted to understand the genetic and environmental factors responsible for the variable penetration of MSH6 germline mutations, as well as to identify other causes of early-onset colorectal cancer
Labormedizinische Leistungen für nichtinfektiöse Enteritis und Kolitis in der vertragsärztlichen Versorgung
Rapid Detection of Sex Chromosomal Aneuploidies by QF-PCR: Application in 200 Men with Severe Oligozoospermia or Azoospermia
Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy
Polymorphisms of the ABCB1 (MDR1) and ABCG2 (BCRP) genes were reported to alter
the expression and function of these drug transporters. Both proteins are present
at the main pharmacokinetic barriers including the blood-brain barrier. Data from
291 children with acute lymphoblastic leukaemia were analysed in this
retrospective study. ABCB1 3435T>C, 2677G>T/A, 1236C>T and ABCG2 421C>A, 34G>A
genotypes were determined. Encephalopathy episodes were more frequent among those
with ABCB1 3435TT genotype than in the 3435CC/CT group (odds ratio (OR) 3.5;
P=0.03). Patients with the ABCG2 421A allele tended to have more complications
than wild type homozygotes (OR=2.0; P=0.25). The rate of the adverse effect was
similar in those harbouring no or only one of the predisposing genotypes, that
is, either ABCB1 3435TT or ABCG2 421AA/AC. However, significantly more children
suffered encephalopathy in the group with both predisposing genotypes (OR=12.3;
P=0.005). In conclusion, these variations exert synergistic effect in
predisposing patients to toxic neurological complications of chemotherapy
The role of ABC-transporter gene polymorphisms in chemotherapy induced immunosuppression, a retrospective study in childhood acute lymphoblastic leukaemia
We examined the association of functional ABCB1 (MDR1) and ABCG2 (BCRP)
polymorphisms with acute side effects of chemotherapy. Analyses were performed on
clinical data from 138 patients treated with the ALL-BFM-95 protocol implying
several substrates of these transporters. ABCB1 3435T>C, 2677G>T/A 1236C>T and
ABCG2 421C>A genotypes were determined. A higher proportion of ABCB1 3435TT
patients suffered excessive infectious complications than those harbouring at
least one C allele (OR=2.5, p=0.03) during the whole half-year-long intensive
phase of chemotherapy. Weaker associations were calculated when ABCB1
1236T-2677T-3435T haplotype homozygotes were tested against the remaining part of
the population (OR=2.3, p=0.09). During the reinduction phase of therapy, the
occurrence of severe leukocytopenia was similar among ABCB1 genotype groups. The
frequency of any toxicities were not shown to differ according to the ABCG2
421C>A genotype. Our data suggest that the ABCB1 3435T>C genotype is associated
with the infectious complications of the applied chemotherapy regimen