NTD Group Research Articles

Correlation of polymorphism of MTHFRs and RFC‐1 genes with neural tube defects in China

Maternal periconceptional supplementation of folate reduces the incidence of neonatal Neural Tube Defects, indicating that changes in folate metabolism play a role in formation of NTDs. The mutations on two genes involved in folate metabolism, the C677 of the MTHFR gene and the RFC-1(A80G) gene are potential risk factors of NTDs. In this study, we analyzed the genotypic distributions and allele frequencies of MTHFR C677T and RFC-1 A80G polymorphisms in DNA samples from mothers with at least one previous child with NTDs (the NTD group) and controls. Our results indicated that there was a significant difference in the genotype and allele frequencies of RFC-1 80A-->G between the NTD group and controls (p = .008 and p = .017, respectively). There was, however, no significant difference in the genotype and allele frequencies of the MTHFR 677C-->T polymorphism between the NTD group and controls. The NTD group was further separated into the upper and lower types by location of abnormalities. The frequency of RFC-1 80A/G and 80G/G was significantly higher in the upper group than the control (p = .009 and p = .005, respectively). The frequency of G-alleles was also significantly higher in the upper group than the control (OR 2.42; p = .006; 95% CI: 1.28-4.58). For the MTHFR C677 gene, the frequency of T-alleles was significantly lower in the lower defect type than the control group (OR 0.32; p = .027; 95% CI: 0.11-0.9). These results suggest that in the Shanxi population RFC-1 polymorphisms may play a role in NTD risk, whereas the impact of MTHFR C677T polymorphisms requires further clarification. Birth Defects Research (Part A) 2008.

An evaluation of maternal illnesses in the origin of neural-tube defects.

The objective of the study was to estimate risk of acute and chronic maternal diseases during pregnancy in the origin of neural-tube defects. Mothers with neural-tube defect fetuses/newborns (the NTD group), controls without any congenital defects (the normal control group) and controls with other defects (the other CA control group) were compared in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Of 1,202 cases with neural tube defects, 559 (49.8%) and 229 (19.1%) had mothers with one or more acute and chronic diseases, respectively. Of 38,151 mothers in the normal control group 14,004 (36.7%) and 8,328 (21.8%) had mothers with one or more acute or chronic diseases, respectively. Of 22,475 mothers in the other CA control group, 8,999 (40.0%) and 3,793 (16.9%) were affected with one or more acute or chronic maternal diseases, respectively. The prevalence of these diseases was evaluated in the 2nd months of gestation, however, if diseases occurred in the 1st month and continued in the 2nd month were also included. There was a potential recall bias between the NTD group and the normal control group, but not between the NTD group and the other CA control group. We suggest that maternal fever is a possible cause of neural-tube defects. Thus, these fevers should be treated with antipyretics during pregnancy. Among chronic maternal diseases, the possible association of migraine-headache, on the one hand and neural tube defects (particularly anencephaly) on the other hand cannot be excluded.

The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma

We evaluated the impact of overall treatment time on the disease-free survival (DFS) and local control after radiotherapy for nonsmall cell lung carcinoma. One hundred fifty-three cases considered as responders to radiotherapy were retrospectively analyzed. Patients with Karnofsky status < 70, pretreated with chemotherapy and with pleural or pericardial effusion, were excluded from the analysis. Radiation dose homogenization was done with calculation of the normalized total dose without (NTD) and with time correction (NTD-T) for alpha/beta = 10 Gy. Kaplan-Meier curves for 2-year DFS showed that any analysis based on radiation dose can prove to be erroneous when the time factor is neglected. Although there was no difference between the 47-55 Gy and 56-64 Gy NTD groups, a log rank test revealed a strong difference (p < 0.0002) between NTD-T groups. No difference was observed for patients with mediastinal involvement. Logistic regression analysis showed a statistical association of dose on 2-year local progression-free probability for different time compartments. For those cases without mediastinal involvement, the daily dose lost because of treatment protraction beyond 20 days after the beginning of radiotherapy was estimated to 0.2 Gy/day. When all cases were considered together this was calculated to 0.45 Gy/day. Time factor should not be underestimated when evaluating the results of radiotherapy for nonsmall cell lung cancer. There is strong evidence that prolonged overall treatment time could be a major cause of the failure of radiotherapy to control the local disease.