The analysis of the interaction between environmental and genetic factors is a matter of increasing interest in cancerology. More particularly the discovery of the BRCAx family and the high cumulated incidence of familial breast cancers related to mutations of these proteins raised the issue of the differential effect of long term and/or early exposure to oral contraceptives in the presence of these mutations. The classical case-control design assumes the presence of a control group, which can be sometimes difficult to obtain from both the technical and ethical points of view. Case-only or case-case studies, which are based only on series of cases, making them apparently attractive, have been proposed to analyze more specifically the interaction term. The aim of the present paper is to review and discuss the methodological basis and main assumptions of the case-only design, and their applicability to breast cancer studies. The measure of the interaction between an environmental factor and a susceptibility genetic factor differs in an important aspect from the measure of the association between an environmental factor and a acquired tumoral genetic factor; this aspect is reminded.

Chromatin restricts the accessibility of DNA to regulatory factors; its remodeling over the regulatory regions contributes to the control of gene expression. An increasing number of evidence links defects in chromatin remodeling machinery and cancer. Our aim is to elucidate the role of chromatin structure in the control of the expression of hormone-induced genes in breast cell lines estrogen-dependent or -independent for growth. Mammary tumor growth is controlled by steroid hormones via their nuclear receptor and by growth factors via tyrosine kinase receptors. 50 % of these tumors elude to hormonal control. This limits the anti-estrogen therapy. As a model, we have analyzed in several cell lines the chromatin organization of the regulatory regions of two genes, pS2 that is associated with a good prognostic, and cathepsin D (catD) that is a bad prognostic marker. The expression of the two genes is estrogen-regulated in estrogen-dependent cell line MCF7. In contrast in the hormone-independent cell line MDA MB 231, pS2 is not expressed and catD is constitutively expressed. Within the regulatory regions of pS2 gene, we have localized two regions that undergo a hormone-dependent change in chromatin structure in MCF7 cells but not in MDA MB 231. The lack of chromatin remodeling in MDA MB 231 cells is not due to the absence of expression of the estrogen receptor in the cell line. The expression of pS2 gene can be correlated with chromatin remodeling over the regulatory regions of pS2 gene. In contrast catD regulatory regions did not display hormone-dependent changes in chromatin structure, suggesting that hormone regulation takes place within regions with a constitutively open chromatin structure.

Human epithelial thyroid radiation-induced tumorigenesis is the most frequent radiation-induced tumorigenic process in man. Results of different studies, concerning the molecular mecanism(s) of epithelial thyroid radiation-associated tumorigenesis show : 1) that there is not a significant difference in the frequency of activation of ras, gsp and trk proto-oncogenes between radiation-associated and <<spontaneous >> thyroid tumors; 2) the relevant role played by RET/PTC ret proto-oncogene activating rearrangements, in the development of radiation-associated thyroid tumors originated after therapeutic radiation (mainly PTC 1) or the atomic accident of Chernobyl (mainly PTC 3) and 3) suggest that the patients who develop thyroid tumors after a history of irradiation, show a genomic instability consisting in a DNA repair defect.

The MTS1 (Multiple Tumor Suppressor 1) locus is a very original one as its organization results in the expression of two alternative transcripts that encode two structurally and functionally different proteins: INK4a and ARF (also designated p19ARF in mouse and p14ARF in man). Recent findings indicate that the latter is a major component of a regulatory pathway of oncogenic signals culminating in p53 activation by stabilisation of the protein. While the importance of this pathway has been overtly established in animal experimental oncology, it still has to be further documented in human oncology in order for this gene to acquire its full biological significance.

Progression in cell cycle is controlled by CDKs (cyclin dependent kinases) and their cyclins regulatory subunits. In mammalian cells, three dual specificity phosphatases called CDC25 activate CDKs/cyclin complexes. The activity of CDC25 is regulated by phosphorylation and dephosphorylation events. CDC25 phosphatases also participate in cell cycle checkpoints activated in response to DNA damage. Two members of this family, CDC25 A and CDC25 B, have oncogenic properties, and their overexpression has been detected in various types of tumors.

We report a family presenting the syndrome initially described by Oley characterized by congenital profus milia and hypotrichosis that regress during adolescence.

Gestational trophoblastic diseases amalgamate several entities with a common denominator which is a hypersecretion of hCG: complete mole, invasive or not, partial mole or triploid syndrome, gestational trophoblastic carcinoma and trophoblastic carcinoma from the implantation site. These entities differ by their origins, their morphology, their evolution and their treatments. Complete moles are diploid and in 80% of cases, chromosomes are only from paternal origin (diandry or dispermy). Their evolution is unpredictable whatever the molecular biology or cytogenetical methods are. Partial moles, generally triploid, are much more frequent (10-20% of miscarriages) than the number of cases diagnosed during the pregnancy. In 85% of cases, two sets of chromosomes are of paternal origin. The gestational trophoblastic carcinoma is diploid and its genetic material comes from both parents. This probably excludes a direct filiation between complete mole and gestational trophoblastic carcinoma. The trophoblastic tumor from the implantation site comes from the trophoblast of the implantation site which explain why its evolution and its prognosis are totally distinct from the previous one. In this report, we successively discuss the natural history of gestational trophoblastic diseases, their epidemiology and the genetic data explaining their origins.

To evaluate prospectively 90 consecutive cases of squamous cell carcinoma of penis, referred to our Institute, by flow cytometry analysis of cellular DNA content. To compare deoxyribonucleic acid (DNA) flow cytometry with clinical and pathological variables to determine the prognostic significance of this analysis to guide the selection of patients at high risk for development of lymph node metastases.

Certain HPV types have transforming properties. These oncogenic activities are related to the abilities of the viral proteins E6 and E7 to inhibit the products of two cellular tumor suppressor genes (p53 and Rb respectively). But the early steps of cervical carcinogenesis are not well known. The goal of our study was to evaluate cervical intraepithelial neoplasia (CIN) for the tumor suppressor genes p53 and pRb, the HPV status and the mitotic activity, in order to better understand the mechanism of carcinogenesis.