Specific BRCA1 gene variations amongst young Moroccan breast cancer patients.

Germline mutations in the BRCA1 gene are known predictive markers for the development of hereditary breast cancer. Nevertheless, no comprehensive study has been performed targeting the presence and relevance of BRCA1 mutations in Moroccan breast cancer patients. We here present an analysis of BRCA1 gene regions (exon 2 and exon 11a/b) of 50 female Moroccan breast cancer patients with early disease onset (≤ 40 years) or familial disease backgrounds. Results showed that no mutation was present in either exon 2 or exon 11a of the BRCA1 gene in any of the 50 patients analysed. However, in exon 11b, a mutation generated by a nucleotide exchange was detected in 8% of patients, most of whom were young women (≤ 40). This mutation leads to substitution of the amino acid glutamine by an arginine at position 356 of the polypeptide sequence (Q356R). Although this mutation was previously characterised at a lower frequency in western populations, our study is the first to describe it in a young Moroccan population. Furthermore, another mutation was detected with a high frequency (4%) on exon 11b of the BRCA1 gene in exclusively young patients (≤ 40). This mutation was silent, encoding the same threonine residue at position 327 (T327T) as the wild type. The present study is the first to describe this mutation as well, particularly in a young Moroccan population. Analysis of a larger population is required in order to highlight the relevance of the Q356R and T327T mutations in young Moroccan breast cancer patients.

Methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk in Moroccan women.

BACKGROUND: Methylenetetrahydrofolate (MTHFR) enzyme plays an important role in folate metabolism which is involved in DNA methylation, repair, and synthesis. OBJECTIVE: We investigated if the MTHFR C677T polymorphism modulates the risk of developing breast cancer in Moroccan women. METHODS: Genotyping was performed by PCR-RFLP method on a sample of 96 patients with breast cancer and 117 controls. RESULTS: A positive correlation was found between the MTHFR C677T polymorphism and progesterone receptors expression (p= 0.04). According to menopausal status, the heterozygous CT (OR = 2.29 and P = 0.03) was statistically significant in pre-menopausal women. There was a significant association between C677T polymorphism and breast cancer risk in both additive (OR = 2.2, 95% CI = 1.24-3.86, p = 0.007) and dominant (OR = 2.10, CI 95% = 1.21-3.64, p = 0.008) models. In addition, the T allele were associated with a high breast cancer risk (OR = 1.59, 95% CI = 1.04-2.44, p = 0.03). CONCLUSION: In the light of our preliminary study, 677T allele and 677CT MTHFR genotype may represent a genetic determinant increasing breast cancer risk in Moroccan women. A larger study including a larger sample size and more information is needed to confirm our conclusions.

[The ethical implications of conserving biological samples]. / Les implications éthiques de la conservation des échantillons biologiques.

The conservation and use of biological samples become more and more frequent all around the world. Biobanks of human body substances (blood, urine, DNA, tissues, cells, etc.), and personal data associated with them are created. They have a double character as they are collections of both human biological samples and personal data. In some cases, the gametes, reproductive tissues, embryos, foetal tissue after abortion or even specimens of dead donors are collected and conserved. Although biobanks raise hopes in both the development of new therapies, new drugs and their integration into clinical medicine, they also point to concerns related to ethical questions such as: the principles of information, the consent of the persons concerned, the confidentiality about the personal data, and in some cases discrimination and stigmatisation. Other ethical aspects could raise gradually as research advance. Research being carried out on human sample requires informed free consent from the person who should be able to consent. The donor must be sufficiently informed about the process of research, the purpose, benefits and the risks involved in participating in this research. In the case of persons unable to give consent such minors or persons with mental disabilities, special measures are undertaken. Once the consent was given, the right of withdrawal has been consistently supported by the various declarations and regulations, but some oppose this right for a number of reasons particularly in the case of research on the samples without risk of physical exposure. In this case the notion of human body integrity is different than in research involving therapeutic or clinical intervention. In the case of withdrawal of consent, the samples should be destroyed, but the anonymous results arising from them and their analysis are not affected. What is the case for future uses? Should the researcher obtain again the consent from the donor for a secondary use of the samples? This is a matter of debate in the public and scientific communities. In Morocco, research activities on humans are undertaken in the absence of legal framework. Among the ethical issues, the most frequent in Morocco are related to the informed and explicit consent. Illiteracy, which concerns half of the population, and the economic vulnerability of the largest proportion of the patient make the informed and explicit consent questionable. In this paper we aimed to describe the use and conservation of human biological samples in Morocco and to determine the ethical questions raised in this context. An anonymous questionnaire was sent to biologists working in the different laboratories. The response rate was only 59.2%. The human biological samples are generally used for diagnosis and clinical follow-up. The storage period ranged from 3 months to 1 year, it does not exceed one year. The percentage of conservation of biological samples in the laboratory for one year is 67% and no basic criterion is maintained in the selection of samples. All laboratories obtained their samples directly from patients; no exchange or duplicate samples were undertaken between institutions. The analyses performed on the stored samples are biochemical and immunological. The genetic analyses accounted for only 35% of the total samples. The laboratories involved a researcy activity accounted for only 13.6%. Some of them answered they had not obtained in a systematic manner the consent of the persons concerned. These results indicated a lack of information and guidance on bioethics in Morocco.