Biomedical subjects

Marie Plante

Publications and source records attributed to Marie Plante.

At least 19 recordsLinked to original sources

PubMed2026

Pragmatic gynecologic cancer clinical trials: statements and roadmap from the Gynecologic Cancer InterGroup Chicago Brainstorming Meeting.

Randomized controlled trials remain fundamental to evidence generation in oncology but are increasingly complex, costly, and often misaligned with real-world practice. Traditional explanatory trials, designed under ideal, controlled conditions, frequently enroll highly selected populations, limiting generalizability and underrepresenting key groups such as older adults, patients with comorbidities, and those from low- and middle-income countries. Pragmatic clinical trials offer an alternative by evaluating interventions under routine care conditions, with broader eligibility, simplified procedures, and patient-centered outcomes. To address these challenges, the Gynecologic Cancer InterGroup convened an international brainstorming meeting in May 2025 with multi-disciplinary experts, patients, and advocates to define priorities and develop a roadmap for pragmatic trials in gynecologic oncology. Key discussions emphasized embedding trial design within routine care, aligning eligibility criteria and procedures with standard practice, minimizing non-essential data collection, and prioritizing outcomes meaningful to patients, including quality of life. Innovative designs such as registry-based randomized trials, trials-within-cohorts, and cluster randomization were highlighted as feasible approaches to improve efficiency while preserving internal validity. Integration of patient-reported outcomes and real-world data was considered achievable when carefully streamlined. Major challenges identified included regulatory heterogeneity, consent complexity, data interoperability, and funding limitations, particularly in multi-national settings. Proposed solutions include simplified consent models, centralized ethics processes, hybrid funding strategies, and the responsible use of artificial intelligence to enhance patient identification, recruitment, and potential development of synthetic control arms. Patient engagement was recognized as essential to ensure relevance, feasibility, and equity. Incorporation of patient-reported outcomes was discussed as key to informing acceptance and tolerability. In summary, pragmatic trials within Gynecologic Cancer InterGroup represent a critical pathway to generate efficient, inclusive, and practice-changing evidence in gynecologic cancers across diverse health care settings.

Humans↗

PubMed2007

Effect of the Women's Health Initiative study publication on hormone replacement therapy use among women who have undergone BRCA1/2 testing.

BACKGROUND: Since the publication, in July 2002, of the Women's Health Initiative (WHI) study, use of hormone replacement therapy (HRT) has decreased substantially in the general population. However, little is known about the effect of WHI study results on HRT use among women at high risk of breast cancer. The purpose of this study is to compare HRT use, prepublication versus postpublication of the WHI study, among women tested for BRCA1/2 mutations. METHODS: Participants were >35 years of age and had received their result of genetic testing (delivered within the interdisciplinary research program Interdisciplinary Health Research International Team on Breast Cancer Susceptibility), no later than February 28, 2005. HRT use was reported in self-administered questionnaires, 1 year after result disclosure. Women returning their questionnaire before July 17, 2002 were classified as pre-WHI, whereas those returning it after October 15, 2002 comprised the post-WHI group. RESULTS: Four hundred fifty-seven women (199 and 258 in the pre-WIH and post-WHI groups, respectively) were included in this analysis. Globally, there was no difference in HRT use between prepublication and postpublication of the WHI study (8% and 11%, respectively; prevalence ratio, 0.74; 95% confidence interval, 0.43-1.28). However, noncarriers of the familial mutation were less likely to use HRT after publication of the WHI study results (9%) than before (21%; P = 0.03). CONCLUSIONS: Overall, HRT use among women tested for BRCA1/2 mutations is relatively low and apparently uninfluenced by the WHI study findings. However, the HRT use reduction among noncarriers is similar to that of women in the general population and consistent with the Canadian Cancer Society's recent HRT use recommendations.

Adult↗

PubMed2006

Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families.

BACKGROUND: Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. METHODS: ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD), haplotype analyses, and tagging SNP (tSNP) identification. Expression analyses were carried out using real-time PCR. RESULTS: The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. CONCLUSION: Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. In addition, our study led to the characterization of a novel Delta33 splice form, which could generate a putative truncated protein lacking several functional domains. Additional studies in large cohorts and other populations will be needed to further evaluate if common and/or rare ATR sequence variants can be associated with a modest or intermediate breast cancer risk.

Adult↗

PubMed2006

Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG.

PURPOSE: Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients. METHODS: Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS). RESULTS: Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted. CONCLUSION: Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.

Adult↗

PubMed2006

Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer.

BACKGROUND AND OBJECTIVE: In clinical settings with fixed resources allocated to predictive genetic testing for high-risk cancer predisposition genes, optimal strategies for mutation screening programmes are critically important. These depend on the mutation spectrum found in the population under consideration and the frequency of mutations detected as a function of the personal and family history of cancer, which are both affected by the presence of founder mutations and demographic characteristics of the underlying population. The results of multistep genetic testing for mutations in BRCA1 or BRCA2 in a large series of families with breast cancer in the French-Canadian population of Quebec, Canada are reported. METHODS: A total of 256 high-risk families were ascertained from regional familial cancer clinics throughout the province of Quebec. Initially, families were tested for a panel of specific mutations known to occur in this population. Families in which no mutation was identified were then comprehensively tested. Three algorithms to predict the presence of mutations were evaluated, including the prevalence tables provided by Myriad Genetics Laboratories, the Manchester Scoring System and a logistic regression approach based on the data from this study. RESULTS: 8 of the 15 distinct mutations found in 62 BRCA1/BRCA2-positive families had never been previously reported in this population, whereas 82% carried 1 of the 4 mutations currently observed in > or =2 families. In the subset of 191 families in which at least 1 affected individual was tested, 29% carried a mutation. Of these 27 BRCA1-positive and 29 BRCA2-positive families, 48 (86%) were found to harbour a mutation detected by the initial test. Among the remaining 143 inconclusive families, all 8 families found to have a mutation after complete sequencing had Manchester Scores > or =18. The logistic regression and Manchester Scores provided equal predictive power, and both were significantly better than the Myriad Genetics Laboratories prevalence tables (p<0.001). A threshold of Manchester Score > or =18 provided an overall sensitivity of 86% and a specificity of 82%, with a positive predictive value of 66% in this population. CONCLUSION: In this population, a testing strategy with an initial test using a panel of reported recurrent mutations, followed by full sequencing in families with Manchester Scores > or =18, represents an efficient test in terms of overall cost and sensitivity.

Adolescent↗

PubMed2006

Negative sentinel lymph node accurately predicts negative status of pelvic lymph nodes in uterine cervix carcinoma.

OBJECTIVE: The significance of negative sentinel lymph nodes (SLN) is important in the staging and treatment of melanoma and a few other cancers, but is controversial in uterine cervix carcinoma. Our study was aimed at correlating the SLN status in cervical carcinoma with non-sentinel lymph nodes (non-SLN), in a uniform and well controlled population. METHODS: This study includes 36 patients with stage I and IIA cervical carcinoma and bilaterally negative SLN on final pathology. SLN were identified using blue dye and radioisotopic techniques. Frozen section examination was performed for all SLN; the rest of the tissue was formalin fixed and paraffin embedded. The protocol used for SLN was also applied for non-SLN. For each block, six 4-micro m thick sections were cut at 40 micro m intervals and stained with H and E; an additional section taken between the 3rd and 4th levels was imunostained using AE1/AE3 cytokeratin. RESULTS: The mean age for the study population was 39 years (range 25-76); the number of SLN ranged from 2 to 6 (mean 2.7) and the non-SLN from 8 to 49 (mean 23) per case. No metastasis was found in any SLN and non-SLN by step sections and IHC. CONCLUSION: Our study demonstrates that bilaterally negative SLN on final pathology accurately predict the absence of metastases in non-SLN in cervical carcinoma. If confirmed by larger trials, these results may influence the clinical management of early cervical cancer.

Adult↗

PubMed2006

Neoadjuvant chemotherapy followed by vaginal radical trachelectomy in bulky stage IB1 cervical cancer: case report.

BACKGROUND: We present 3 young women with bulky stage IB1 cervical cancer treated with neoadjuvant chemotherapy followed by laparoscopic pelvic node dissection and vaginal radical trachelectomy. CASES: In the last year, we have treated 3 young women with large cervical lesions who wished to preserve fertility with induction chemotherapy followed by fertility-sparing surgery. They all had lesions measuring 3 to 4 cm and felt to be too big to safely undergo a radical trachelectomy. Three cycles of platinum-based combination chemotherapy were given and were well tolerated. The 3 patients had a significant clinical response to chemotherapy. A complete pathological response was confirmed by the absence of residual invasive cancer in the three trachelectomy specimens. There has been no recurrence so far and no pregnancy yet. CONCLUSION: Neoadjuvant chemotherapy followed by a fertility-sparing surgery may become a valuable option for young women with bulky stage IB1 cervical cancer who wish to preserve their fertility potential.

Adult↗

PubMed2006

Characterization of common UGT1A8, UGT1A9, and UGT2B7 variants with different capacities to inactivate mutagenic 4-hydroxylated metabolites of estradiol and estrone.

The oxidative metabolism of estrone (E1) and estradiol (E2) to form carcinogenic 4-hydroxy-catecholestrogens (4-OHCE) is associated with uterine and breast carcinogenesis. In this study, we conducted functional analyses of genetic variants in the UDP-glucuronosyltransferase UGT1A8, UGT1A9, and UGT2B7 enzymes primarily involved in the inactivation of 4-OHCEs. Compared with UGT2B7*2 (H268Y), UGT2B7*1 exhibited a 2-fold lower efficiency (intrinsic clearance) at conjugating 4-hydroxyestrone and 4-hydroxyestradiol at positions 3 and 4 caused by altered capacities (Vmax) and affinities (Km). The -79 G>A promoter variation, characterizing the UGT2B7*2g haplotype, leads to a 50% reduction of transcription (P < 0.001) in human endometrial carcinoma-1B cells. Furthermore, a >12-fold decreased intrinsic clearance of the *1 proteins was induced by selected amino acid substitutions in UGT1A8 (*3 C277Y) and UGT1A9 (*3 M33T). Frequencies of the low-activity alleles in Caucasians were 45% for UGT2B7*1, 5% for the -79A promoter variant, 1.2% for UGT1A8*3, and 2.2% for UGT1A9*3. Supporting a protective role in two organs sensitive to 4-OHCE-induced damages, the expression of UGT enzymes was shown by immunohistochemistry in normal breast and endometrial tissues and confirmed by Western blotting in a subset of samples. Altogether, findings suggest that specific polymorphisms in UGT genes may modulate the exposure to carcinogenic metabolites of E2 and potentially lead to an altered risk of breast and endometrial cancers in women carrying the variant alleles.

Biotransformation↗

PubMed2006

Partnering in oncogenetic research--the INHERIT BRCAs experience: opportunities and challenges.

Today it is common to conduct research in collaboration with colleagues from different disciplines and institutions. The INterdisciplinary HEalth Research International Team on BReast CAncer susceptibility (INHERIT BRCAs), involves Canadian and international experts from diverse fields working with health service providers, patients and collaborators from the World Health Organization and other European networks. Evidence-based information and knowledge transfer drive our efforts to advance genomic research to understand the genetic basis of cancer susceptibility and treatment response. Several goals reveal the interdisciplinary team approach: (a) to estimate the prevalence and penetrance of BRCA1 and BRCA2 mutations and their deleterious impact upon different populations; (b) to pinpoint novel breast cancer susceptibility loci; (c) to assess the efficacy of clinical interventions; (d) to address changes in quality of life and health-related behaviour from the decision to undergo genetics testing and during follow-up; (e) to evaluate legal, social and ethical implications; and, finally; (f) to promote professional and public education by facilitating the transfer of research findings to clinical practice and informing policy makers. The lessons learned by the INHERIT research team and future challenges are presented.

Breast Neoplasms↗

PubMed2006

No Evidence of BRCA1/2 genomic rearrangements in high-risk French-Canadian breast/ovarian cancer families.

The discovery of deleterious mutations in the breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, has facilitated the identification of individuals at particularly high risk of these diseases. There is a wide variation between populations in the prevalence and related risks of various types of BRCA1/2 mutations, so estimates cannot be extrapolated to Canadians, especially not founder populations such as French- Canadians. Polymerase chain reaction (PCR)-based methods were used to detect the majority of these mutations. These approaches usually failed to detect large DNA rearrangements, which have been claimed to be involved in other populations in 5% to up to 36% of BRCA1-positive families. There is very little information about the contribution of this type of mutation in BRCA2-positive families. To investigate if our available mutation spectrum of BRCA1 and BRCA2 in high-risk French-Canadian breast/ovarian cancer families has been biased by PCR-based direct sequencing methods, we first used Southern blot analysis to test DNA samples from 61 affected/obligate carrier individuals from 58 families in which no BRCA1/2 deleterious mutation was found. Finally, 154 individuals from 135 BRCA1/2 nonconclusive families, including all those tested previously by Southern blot analysis, were tested with the new multiplex ligation probe amplification (MLPA) technique. These approaches failed to detect any rearrangement. Moreover, if the frequency of MLPA-detectable rearrangements in our cohort of 135 BRCA1/2 nonconclusive families was 2.2% or higher, we would have had a 95% or greater chance of observing at least one such rearrangement. As no rearrangements were identified, such large rearrangements must be quite rare in our population.

Blotting, Southern↗

PubMed2006

Fertility-preserving options for cervical cancer.

Childbearing is one of the most important life goals for many women, and fertility preservation is a very important factor in the overall quality of life of cancer survivors. Cervical cancer frequently affects young women; because some women tend to delay childbearing, fertility preservation must be considered when treatment options are discussed. Over the past decade, the radical trachelectomy procedure has become a well established fertility-preserving option for young women with early-stage cancer; this procedure is associated with low morbidity, good oncologic outcome, and a high proportion of pregnancies that reach the third trimester and babies that are delivered at term. This article will review available literature on the vaginal radical trachelectomy procedure and data from other surgical approaches, such as the abdominal radical trachelectomy. In addition, the potential future application of neoadjuvant chemotherapy followed by fertility-preserving surgery in patients with locally advanced cervical cancer will be examined. Finally, ultraconservative surgical approaches (eg, conization alone with or without laparoscopic lymphadenectomy) in very early-stage disease will be discussed.

Abdomen↗

PubMed2006

Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors.

Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in paired tumor samples taken prior to and after CT treatment from 6 patients with predominantly advanced stage, high-grade epithelial ovarian cancer. A subset of differentially expressed genes was selected from all microarray data by initial filtering on confidence at p=0.05, followed by filtering on expression level (>or=2-fold). Using these selection criteria, we found 121 genes to be commonly up-regulated and 54 genes to be down-regulated in the post-CT tumors, compared to primary tumors. Up-regulated genes in post-CT tumors included substantial number of genes with previously known implication in mechanisms of chemoresistance (TOP2A, ETV4, ABCF2, PRDX2, COX2, COX7B, MUC1, MT3, MT2A), and tumorigenesis (SCGB2A2, S100A9, YWHAE, SFN, ATP6AP1, MGC5528, ASS, TACC3, ARHGAP4, SRA1; MGC35136, PSAP, SPTAN1, LGALS3BP, TUBA4, AMY2B, PPIA, COX1, GRB2, CTSL). Down-regulated genes in post-CT samples mostly included genes implicated in chemosensitivity (GRP, TRA1, ADPRTL1, TRF4-2), cell proliferation and cell cycle control (NGFRAP1, TPD52L1, TAX1BP1) and tumor suppression and apoptosis (SMOC2, TIMP3, AXIN1, CASP4, P53SCV). Additionally, gene clustering analysis revealed the existence of two distinct expression signatures of chemoresistant tumors, which was further confirmed by assessment of some genetic (p53 gene mutation status) and clinical parameters (CT regimens). Our data suggest that intrinsic and acquired chemoresistant phenotypes of post-CT tumors may be attributed to the combined action of different factors implicated in mechanisms of chemoresistance, tumor invasion/progression and control of cell proliferation. This type of molecular profiling could have important clinical implications in resolving chemoresistance and the development of novel treatment strategies designed to prevent its emergence.

Adult↗

PubMed2006

Gene expression patterns of chemoresistant and chemosensitive serous epithelial ovarian tumors with possible predictive value in response to initial chemotherapy.

Chemotherapy (CT) resistance in ovarian cancer is broad and encompasses diverse, unrelated drugs, suggesting more than one mechanism of resistance. We aimed to analyze the gene expression patterns in primary serous epithelial ovarian cancer (EOC) samples displaying different responses to first-line CT in an attempt to identify specific molecular signatures associated with response to CT. Initially, the expression profiles of 15 chemoresistant serous EOC tumors [time to recurrence (TTR) </=6 months] and 10 chemosensitive serous EOC tumors (TTR > or =30 months) were independently analyzed which allowed the identification of specific sets of differentially expressed genes that might be functionally implicated in the evolution of the chemoresistant or the chemosensitive phenotype. Our data suggest that the intrinsic chemoresistance in serous EOC cells may be attributed to the combined action of different molecular mechanisms and factors linked with drug influx and efflux and cell proliferation, as possible implications of other molecular events including altered metabolism, apoptosis and inflammation cannot be excluded. Next, gene expression comparison using hierarchical clustering clearly distinguished chemosensitive and chemoresistant tumors from the 25 serous EOC samples (training set), and consecutive class prediction analysis was used to develop a 43-gene classifier that was further validated in an independent cohort of 15 serous EOC patients and 2 patients with other ovarian cancer histotypes (test set). The 43-gene predictor set properly classified serous EOC patients at high risk for early (< or =22 months) versus late (>22 months) relapse after initial CT. Thus, gene expression array technology can effectively classify serous EOC tumors according to CT response. The proposed 43-gene model needs further validation.

Aged↗

PubMed2005

A new alternative splice variant of BRCA1 containing an additional in-frame exon.

The breast/ovarian cancer susceptibility gene BRCA1 interact with multiple protein complexes involved in cellular mechanisms, such as DNA repair, transcription, homologous recombination and cell cycle regulation. Extensive analyses over the past decade led to the detection of several BRCA1 alternative splice variants. Here, we identify the first BRCA1 alternative splice variant containing an additional in-frame exon. This previously unknown exon 13A-containing transcript is generated by the insertion of 66 nucleotides between exons 13 and 14, due to alternative splicing in intron 13 (IVS13-2786-2720). Furthermore, exon 13A-containing transcript was detectable in total RNA samples from 12 normal tissues and several breast and other cancer cell lines. As revealed by real-time PCR analysis, this transcript corresponds to 20 to 25% of the total BRCA1 mRNA expression levels in leukocytes, brain and cerebellum tissues, whereas its relative level of expression is less than 5% in other tested tissues and cancer cell lines. This novel alternative transcript adds 22 amino acids after residue 1452, thus modifying the primary structure of the trans-activation domain 1 (AD1) and the protein-protein interacting domain of BRCA1 with BRCA2, AR and MSH2. No sequence variant has been detected by direct genomic sequencing of exon 13A in individuals originating from high-risk breast/ovarian cancer families.

Alternative Splicing↗

PubMed2005

Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer.

PURPOSE: To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells. PATIENTS AND METHODS: This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated--a 50-mg and a 200--mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. RESULTS: One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, stomatitis) toxicity, asthenia, and rash. No responses were observed. Stable disease was confirmed in 34% and 26% of patients in the 200-mg and 50-mg arms, respectively, and 1-year survival rates were 38.5% and 37.7%, respectively. Baseline erbB3 and erbB4 revealed the highest frequencies of expression, while erbB2 was the lowest. CONCLUSION: CI-1033 did not show activity in unscreened patients with advanced ovarian cancer. At 50 mg/d, CI-1033 had a more favorable adverse events profile than at 200 mg/d. erbB3 and erbB4 receptors showed the highest expression in tumor samples while erbB2 revealed the least. There appears to be no association between baseline erbB expression and disease stability.

Administration, Oral↗

PubMed2005

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families.

The Quebec population contains about six-million French Canadians, descended from the French settlers who colonized "Nouvelle-France" between 1608 and 1765. Although the relative genetic contribution of each of these founders is highly variable, altogether they account for the major part of the contemporary French-Canadian gene pool. This study was designed to analyze the role of this founder effect in the introduction and diffusion of the BRCA1 recurrent R1443X mutant allele. A highly conserved haplotype, observed in 18 French-Canadian families and generated using 17 microsatellite markers surrounding the BRCA1 locus, supports the fact that the R1443X mutation is a founder mutation in the Quebec population. We also performed haplotyping analysis of R1443X carriers on 19 other families from seven different nationalities; although the same alleles are shared for three markers surrounding the BRCA1 gene, distinct haplotypes were obtained in four families, suggesting multiple origins for the R1443X mutation. Ascending genealogies of the 18 French Canadian families and of controls were reconstructed on an average depth of 10 generations. We identified the founder couple with the highest probability of having introduced the mutation in the population. Based on the descending genealogy of this couple, we detected the presence of geographical concentration in the diffusion pattern of the mutation. This study demonstrates how molecular genetics and demogenetic analyses can complement each other to provide findings that could have an impact on public health. Moreover, this approach is certainly not unique to breast cancer genetics and could be used to understand other complex traits.

Alleles↗

PubMed2005

Laparoscopically assisted vaginal radical hysterectomy.

Young patients affected by an early-stage invasive cancer of the cervix are usually treated by surgery. Abdominal radical hysterectomy with pelvic lymphadenectomy is the most widely used technique. With the advent of more conservative surgical approaches, laparoscopy has gained acceptance in gynecologic oncology, opening the way for radical vaginal surgery for cervical cancer. Before this technique becomes widely accepted, it has to be demonstrated that the results, in terms of safety and efficacy, are comparable with the 'standard' abdominal approach. In this chapter we review the technique of laparoscopically assisted radical vaginal hysterectomy and evaluate results of published series.

Female↗

PubMed2005

Vaginal radical trachelectomy: a valuable fertility-preserving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature.

OBJECTIVE: To report the obstetrical results following vaginal radical trachelectomy (VRT), a fertility-preserving surgery in the treatment of early-stage cervical cancer. METHODS: Retrospective review of our first 72 patients treated by a laparoscopic pelvic lymphadenectomy followed by a VRT from October 1991 to October 2003 with regards to their reproductive function. RESULTS: Patients' median age was 32 years old (21-42) and 53 (74%) were nulligravida. A total of 50 pregnancies occurred in 31 women. The majority (66%) had only one pregnancy, 19% had 2 pregnancies and 16% had 3 pregnancies or more. The rate of first trimester miscarriage was 16%, the rate of second trimester miscarriage was (4%) and 2 women (4%) elected to have pregnancy termination. A total of 36 pregnancies (72%) reached the third trimester. Of those, 3 (8%) ended prematurely at <32 weeks gestation, 5 (14%) delivered between 32 and 36 weeks and 28 (78%) delivered at term (>37 weeks). One newborn died of neonatal sepsis from E. coli infection and one died from cardiac malformation (trisomy-18). Seven patients (10%) had infertility problems: 3 from ovulatory causes of which 2 successfully conceived with IVF, one from endometriosis and low sperm count and 3 from probable cervical cause of which one conceived with IUI. One patient had a twin pregnancy following IVF and elected to have embryo reduction and subsequently delivered at 37 weeks. CONCLUSION: Based on our experience, the obstetrical results following VRT for early-stage cervical cancer are very encouraging. The majority of women can anticipate to conceive spontaneously and deliver near term.

Adult↗