Biomedical subjects

Diane Provencher

Publications and source records attributed to Diane Provencher.

At least 19 recordsLinked to original sources

PubMed2007

Global analysis of chromosome X gene expression in primary cultures of normal ovarian surface epithelial cells and epithelial ovarian cancer cell lines.

The interpretation of loss of heterozygosity (LOH) in cancers is complicated as genes that map to LOH regions may be transcriptionally active (Xa) or inactive (Xi) due to X chromosome inactivation (XCI). We have analyzed the chromosome X transcriptome in four epithelial ovarian cancer (EOC) cell lines (TOV21G, TOV81D, TOV112D, and OV90) and 12 primary cultures of normal ovarian surface epithelial (NOSE) cells in relation to chromosome X integrity. Two-way comparative analysis using HuGeneFL Affymetrix GeneChips of TOV21G, TOV81D and OV90 relative to the NOSE samples was highly correlated (> 89%) in contrast to that of TOV112D (56-69%). TOV112D, followed by TOV21G, exhibited the largest number of up-regulated genes. XIST expression by RT-PCR was not detectable in TOV112D or TOV21G. Allele-specific transcription by cDNA sequence analysis of genes known to be subjected to XCI revealed maintenance of XCI in TOV81D and OV90, but not TOV21G. Biallelic expression could not be assessed in TOV112D due to reduction to hemizygosity of chromosome X. Chromosome X rearrangements were observed in FISH analysis of TOV112D and TOV21G, and both of these EOC cell lines were negative for Barr body analysis. The differentially expressed genes did not appear to map to any particular region of the X chromosome in any EOC cell line. The absence of XIST expression is consistent with Barr body loss in TOV112D and TOV21G. The combined evidence is consistent with two proposed mechanisms to account for absence of Xi in female cancers: Xi loss followed by Xa duplication (exemplified by TOV112D) and transcriptional reactivation of Xi (exemplified by TOV21G). Despite an alteration in XIST expression and differences in allelic content in the EOC cell lines, the chromosome X transcriptome was modified modestly when compared with that of NOSE samples.

Cell Line, Tumor↗

PubMed2006

Haplotype analysis suggest common founders in carriers of the recurrent BRCA2 mutation, 3398delAAAAG, in French Canadian hereditary breast and/ovarian cancer families.

BACKGROUND: The 3398delAAAAG mutation in BRCA2 was recently found to recur in breast and/or ovarian cancer families from the French Canadian population of Quebec, a population that has genetic attributes consistent with a founder effect. To characterize the contribution of this mutation in this population, this study established the frequency of this mutation in breast and ovarian cancer cases unselected for family history of cancer, and determined if mutation carriers shared a common ancestry. METHODS: The frequency was estimated by assaying the mutation in series of French Canadian breast cancer cases diagnosed before age 41 (n = 60) or 80 (n = 127) years of age, and ovarian cancer cases (n = 80) unselected for family history of cancer by mutation analysis. Haplotype analysis was performed to determine if mutation carriers shared a common ancestry. Members from 11 families were analyzed using six polymorphic microsatellite markers (cen-D13S260-D13S1699-D13S1698-D13S1697-D13S1701-D13S171-tel) spanning approximately a 3.6 cM interval at the chromosomal region 13q13.1, which contains BRCA2. Allele frequencies were estimated by genotyping 47 unaffected female individuals derived from the same population. Haplotype reconstruction of unaffected individuals was performed using the program PHASE. RESULTS: The recurrent BRCA2 mutation occurred in 1 of 60 (1.7%) women diagnosed with breast cancer before 41 years of age and one of 80 (1.3%) women with ovarian cancer. No mutation carriers were identified in the series of breast cancer cases diagnosed before age 80. Mutation carriers harboured one of two haplotypes, 7-3-9-3 - [3/4]-7, that varied with marker D13S1701 and which occurred at a frequency of 0.001. The genetic analysis of D13S1695, a polymorphic marker located approximately 0.3 cM distal to D13S171, did not favour a genetic recombination event to account for the differences in D13S1701 alleles within the haplotype. Although mutation carriers harbour genotypes that are frequent in the French Canadian population, neither mutation-associated haplotype was plausible in reconstructed haplotypes of 47 individuals of French Canadian descent. CONCLUSION: These results suggest that mutation carriers share a related ancestry; further supporting the concept that recurrent BRCA1 and BRCA2 mutations in the French Canadian population could be attributed to common founders. This finding provides further support for targeted screening of recurrent mutations in this population before large-scale mutation analyses are performed.

Adult↗

PubMed2006

High-risk human papillomavirus infection of the genital tract of women with a previous history or current high-grade vulvar intraepithelial neoplasia.

Human papillomavirus (HPV) infection is associated with high-grade vulvar intraepithelial neoplasia (VIN-3). The prevalence of anogenital HPV infection in women with previously treated VIN-3 has not been documented yet. This cross-sectional study compared high-risk HPV DNA detection rates in women with past (n = 30) and current (n = 22) VIN-3 to those without current or past VIN (n = 86). HPV DNA was detected in vulvar and cervical samples with Hybrid Capture 2 (HC-2). Smoking was associated in multivariate analysis with current VIN-3 (odds ratio (OR) 8.3, 95% confidence interval (CI) 2.0-8.2) and any VIN-3 history (OR 6.5, 95% CI 2.5-16.5). High-risk HPV DNA was found on the vulva of 64%, 33%, and 20% of women with current VIN-3, past VIN-3, and without previous or current VIN, respectively. After controlling for age and smoking, high-risk HPV vulvar infection was associated with cervical high-risk HPV infection (OR 8.6, 95% CI 2.8-26.5; P = 0.001). After controlling for age, HPV infection was more often multifocal in women with current VIN-3 compared to women with previous but no current VIN-3 lesion (OR 17.6, 95% CI 1.4-227.2). Multifocal vulvar HPV infection was detected in women with previous or active VIN-3. Longitudinal studies are required to determine if the multifocality of HPV infection on the vulva could explain the high recurrence rate of VIN-3.

Adolescent↗

PubMed2005

Salvage treatment with high-dose-rate brachytherapy for isolated vaginal endometrial cancer recurrence.

OBJECTIVE: To evaluate the outcome of patients with recurrent vaginal endometrial cancer treated with high-dose-rate brachytherapy (HDRB) and external beam radiation therapy (EBRT). MATERIALS AND METHODS: The records of all patients diagnosed with endometrial cancer who had presented an isolated vaginal recurrence in our institution between January 1, 1997 and December 30, 2003 were reviewed. Twenty-two patients were identified; 18 (82%) received both EBRT and HDRB, and 4 (18%) received HDRB only. The median EBRT dose prescribed was 45 Gy (range: 44-50.4), and median HDRB was 26 Gy (range: 8-48). Recurrence-free intervals as well as disease-specific survival rates were noted. Complications were assessed in terms of early and late Radiation Therapy Oncology Group toxicity (grade 3 or worse) of the gastrointestinal tract, genitourinary tract and vagina. RESULTS: Median age at recurrence for the 22 patients was 72 years (range: 54-86). Median recurrence time was 20 months (range: 4-135). A complete response was achieved in 100% of patients. After a median follow-up of 32 months (range: 11-78), no patient had locoregional recurrence; 1 developed distant metastasis and died from the disease. Five-year local control, disease-free survival and disease-specific survival were 100%, 96% and 96%, respectively. Four patients (18%) presented grades 3-4 gastrointestinal toxicity, and 11 (50%), grade 3 vaginal toxicity. CONCLUSION: Recurrent vaginal endometrial cancer is amenable to salvage therapy with HDRB and EBRT.

Aged↗

PubMed2005

Self-sampling is associated with increased detection of human papillomavirus DNA in the genital tract of HIV-seropositive women.

BACKGROUND: Analysis of self-collected swab samples from the genital tract could improve accrual and retention of women in studies of human papillomavirus (HPV) infection and precancerous cervical lesions. Self-collected vaginal swab specimens and physician-collected cervical swab specimens were compared for detection and typing of HPV DNA in 158 HIV-seropositive women. METHODS: Paired samples were collected for 157 participants. Beta-globin was not detected in 6 (3.3%) physician-collected specimens and 8 (4.3%) self-obtained specimens collected from 11 women, leaving 146 paired samples suitable for PCR analysis. HPV DNA was amplified with the HPV primers PGMY09 and PGMY11 and typed using the line blot assay. RESULTS: HPV DNA was detected more frequently in self-collected samples (95 [65.1%] of 146), compared with physician-collected samples (78 [53.4%] of 146) (P = .04). Self-collected samples contained a greater number of types (mean +/- SD, 1.60 +/- 1.80 types; 95% confidence interval [CI], 1.31-1.90), compared with physician-collected samples (mean +/- SD, 1.25 +/- 1.66 types; 95% CI, 0.98-1.52) (P = .04). A good agreement between sampling methods was achieved for detection of any HPV DNA (kappa = 0.73; 95% CI, 0.58-0.89), high-risk types (kappa = 0.84; 95% CI, 0.68-0.99), and low-risk types (kappa = 0.71; 95% CI, 0.67-0.75). Agreement between sampling methods for detection of HPV DNA was found for 24 (88.8%) of 27 follow-up samples collected from a total of 20 women. A comparison of samples collected at consecutive visits revealed agreements for detection of any HPV DNA, detection of high-risk HPV, and HPV typing results between visits of 88.9% (24 of 27 samples), 81.5% (22 of 27), and 55.5% (15 of 27), respectively, for physician-collected samples, and 96.3% (26 of 27 samples), 92.6% (25 of 27), and 55.5% (15 of 27), respectively, for self-collected samples. CONCLUSION: Analysis of self-collected vaginal swab samples improved the detection rate of HPV, suggesting that such samples might be of greater value than physician-obtained samples in studies of HPV transmission.

Adolescent↗

PubMed2005

Loss of heterozygosity and transcriptome analyses of a 1.2 Mb candidate ovarian cancer tumor suppressor locus region at 17q25.1-q25.2.

Loss of heterozygosity (LOH) analysis was performed in epithelial ovarian cancers (EOC) to further characterize a previously identified candidate tumor suppressor gene (TSG) region encompassing D17S801 at chromosomal region 17q25.1. LOH of at least one informative marker was observed for 100 (71%) of 140 malignant EOC samples in an analysis of 6 polymorphic markers (cen-D17S1839-D17S785-D17S1817-D17S801-D17S751-D17S722-tel). The combined LOH analysis revealed a 453 kilobase (Kb) minimal region of deletion (MRD) bounded by D17S1817 and D17S751. Human and mouse genome assemblies were used to resolve marker inconsistencies in the D17S1839-D17S722 interval and identify candidates. The region contains 32 known and strongly predicted genes, 9 of which overlap the MRD. The reference genomic sequences share nearly identical gene structures and the organization of the region is highly collinear. Although, the region does not show any large internal duplications, a 1.5 Kb inverted duplicated sequence of 87% nucleotide identity was observed in a 13 Kb region surrounding D17S801. Transcriptome analysis by Affymetrix GeneChip and reverse transcription (RT)-polymerase chain reaction (PCR) methods of 3 well characterized EOC cell lines and primary cultures of normal ovarian surface epithelial (NOSE) cells was performed with 32 candidates spanning D17S1839-D17S722 interval. RT-PCR analysis of 8 known or strongly predicted genes residing in the MRD in 10 EOC samples, that exhibited LOH of the MRD, identified FLJ22341 as a strong candidate TSG. The proximal repeat sequence of D17S801 occurs 8 Kb upstream of the putative promoter region of FLJ22341. RT-PCR analysis of the EOC samples and cell lines identified DKFZP434P0316 that maps proximal to the MRD, as a candidate. While Affymetrix technology was useful for initially eliminating less promising candidates, subsequent RT-PCR analysis of well-characterized EOC samples was essential to prioritize TSG candidates for further study.

Chromosome Mapping↗

PubMed2005

Proteome profiling of human epithelial ovarian cancer cell line TOV-112D.

A proteome profiling of the epithelial ovarian cancer cell line TOV-112D was initiated as a protein expression reference in the study of ovarian cancer. Two complementary proteomic approaches were used in order to maximise protein identification: two-dimensional gel electrophoresis (2DE) protein separation coupled to matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and one-dimensional gel electrophoresis (1DE) coupled to liquid-chromatography tandem mass spectrometry (LC MS/MS). One hundred and seventy-two proteins have been identified among 288 spots selected on two-dimensional gels and a total of 579 proteins were identified with the 1DE LC MS/MS approach. This proteome profiling covers a wide range of protein expression and identifies several proteins known for their oncogenic properties. Bioinformatics tools were used to mine databases in order to determine whether the identified proteins have previously been implicated in pathways associated with carcinogenesis or cell proliferation. Indeed, several of the proteins have been reported to be specific ovarian cancer markers while others are common to many tumorigenic tissues or proliferating cells. The diversity of proteins found and their association with known oncogenic pathways validate this proteomic approach. The proteome 2D map of the TOV-112D cell line will provide a valuable resource in studies on differential protein expression of human ovarian carcinomas while the 1DE LC MS/MS approach gives a picture of the actual protein profile of the TOV-112D cell line. This work represents one of the most complete ovarian protein expression analysis reports to date and the first comparative study of gene expression profiling and proteomic patterns in ovarian cancer.

Cell Line, Transformed↗

PubMed2005

Identification of novel variant, 1484delG in the 3'UTR of H3F3B, a member of the histone 3B replacement family, in ovarian tumors.

Previous studies have implicated the chromosomal region at 17q25 as harboring tumor suppressor genes based on the frequent loss of heterozygosity (LOH) observed in epithelial ovarian cancers (EOC). RT-PCR validation of Affymetrix GeneChip expression of H3F3B, a member of the 3B histone family that maps to 17q25.1, revealed a doublet band in cDNA from one of four EOC cell lines, OV90. In contrast to three other EOC cell lines (TOV81D, TOV112D and TOV21G) and primary cultures derived from normal ovarian surface epithelial cells (NOSE), sequence analysis of the cDNA revealed a deletion of G at position 1484 of the transcribed sequence which is located within the 3'UTR of H3F3B. OV90 was derived from ascites fluid of an undifferentiated adenocarcinoma of ovarian origin. The variant allele was identified in 1 of 65 (2%) healthy women with no prior history of cancer and in 5 participants with ovarian tumors comprising of 4 of 79 (5%) malignant EOC, none of 10 low malignancy potential tumors, and 1 of 8 (13%) benign tumors. All carriers of the variant alleles were heterozygous and tumor samples did not exhibit preferential LOH of the normal allele. The variant allele was identified in EOC samples of clear cell (1 of 20), mucinous (1 of 8), mixed cell (1 of 3) and undifferentiated (1 of 2) histopathological subtypes but none of 34 serous or 12 endometrioid subtype tumors. One of 3 mucinous benign tumors also harbored the variant allele. The functional significance of the variant is unknown, however its presence in rare subtypes of ovarian epithelial tumors warrants further investigation.

3' Untranslated Regions↗

PubMed2005

OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer.

A Ser326Cys amino acid variant encoded by OGG1 that removes the highly mutagenic 8-oxo-7,8-dihydroguanine adducts resulting from the oxidative damage produced by reactive oxygen species, has been suggested to reduce activity of the enzyme and result in an increase in G:C --> T:A transversions. Carriers homozygous for the Cys326 variant have been associated with increased risk in some cancers. In this study, we tested the association of this polymorphism with epithelial ovarian cancer (EOC) (n=91 cases) in comparison with women unaffected by the disease (n=57). Although the genotype encoding the homozygous Cys326 variant was found more often in cases (11%) than controls (9%), this was not statistically significant (p=0.297). As OGG1 at chromosome band 3p25.3 overlaps a region exhibiting allelic imbalance (AI) in EOC, we also examined the frequency of AI of the OGG1 locus and its association with somatic mutations in the TP53 tumor suppressor gene, which is frequently mutated in EOC. The frequency of AI and TP53 mutations in EOC was 32 and 37%, respectively. Although the proportion of EOC cases harboring the genotype homozygous for Cys326 was greater in TP53 mutation-positive cases (5 of 34, 15%) than mutation-negative cases (5 of 57, 9%), the distribution of genotypes was not significantly different (p=0.289). Four of the six heterozygous Ser326/Cys326 samples exhibiting AI, displayed loss of the Ser326 variant. About 16% of samples exhibited both AI of the OGG1 locus and a TP53 mutation. Proportionately more EOC samples harbored a mutation in the group of samples exhibiting AI (15 of 29, 52%) in comparison to the group of samples with no AI (19 of 62, 31%) (p=0.036). Although the OGG1 Cys326 variant appears to play a minor role in conferring increased risk of ovarian cancer, the observed AI of the OGG1 locus in association with TP53 somatic mutations warrants further investigation in this disease.

Allelic Imbalance↗

PubMed2004

Significant proportion of breast and/or ovarian cancer families of French Canadian descent harbor 1 of 5 BRCA1 and BRCA2 mutations.

In 1998, we reported that a significant proportion of breast and/or ovarian cancer families of French Canadian descent harbor specific germline mutations in BRCA1 or BRCA2 attributed to common founders. Here we report the frequency of previously described mutations (n = 7) and 13 mutations identified in French Canadian families since 1998, in a new group of families (n = 88). Four of the previously described mutations, 4446C>T, 2953delGTAinsC, 8765delAG and 6085C>T, account for 72% and 69% of mutation-positive families in previously (n = 81) and recently ascertained groups, respectively. Only 2 of 13 recently identified mutations were found in more than 1 family: 3875delGTCT (n = 2) and 3398delAAAAG (n = 4). The 2 groups (ascertained pre- and post-gene discovery) did not differ significantly when distribution of mutations based on cancer syndrome phenotype and age of diagnosis or number of breast cancer cases were compared. Five common mutations accounted for a significant proportion (84%) of all mutation-positive families. The age of diagnosis of female breast cancer in mutation-negative families was significantly higher than that of the mutation-positive families (p<0.0001). The total number of cases of cancer per family was significantly lower in mutation-negative than mutation-positive families (p<0.001). Our results define a new mutation panel for screening BRCA1/2 mutations and the phenotype of mutation-positive families harboring the common mutations in the French Canadian population.

Adult↗

PubMed2004

Gene expression microarray analysis and genome databases facilitate the characterization of a chromosome 22 derived homogeneously staining region.

Karyotype and fluorescence in situ hybridization (FISH) analyses previously identified a homogeneously staining region (HSR) derived from chromosome 22 in OV90, an epithelial ovarian cancer (EOC) cell line. Affymetrix expression microarrays in combination with the UniGene and Human Genome Browser databases were used to identify the candidate genes comprising the amplicon of the HSR, based on comparison of expression profiles of OV90, EOC cell lines lacking HSRs and primary cultures of normal ovarian surface epithelial (NOSE) cells. A group of probe sets displaying a minimum 3-fold overexpression with a high reliability score (P-call) in OV90 were identified which represented genes that mapped within a 1-2 Mb interval on chromosome 22. A large number of probe sets, some of which represent the same genes, displayed no evidence of overexpression and/or low reliability scores (A-call). An investigation of the probe set sequences with the Affymetrix and Sanger Institute Chromosome 22 Group databases revealed that some of the probe sets displaying discordant results for the same gene were complementary to intronic sequences and/or the antisense strand. Microarray results were validated by RT-PCR. Genomic analysis suggests that the HSR was derived from the amplification of a 1.1 Mb interval defined by the chromosomal map positions of ZNF74 and Hs.372662, at 22q11.21. The deduced amplicon is derived from a complex region of chromosome 22 that harbors low-copy repeats (LCRs). The amplicon contains 18 genes as likely targets for gene amplification. This study illustrates that large-scale expression microarray analysis in combination with genome databases is sufficient for deducing target genes associated with amplicons and stresses the importance of investigating probe set design before engaging in validation studies.

Cell Line, Tumor↗

PubMed2004

The effect of music on the neurohormonal stress response to surgery under general anesthesia.

UNLABELLED: Several pharmacological interventions reduce perioperative stress hormone release during surgery under general anesthesia. Listening to music and therapeutic suggestions were also studied, but mostly in awake patients, and these have a positive effect on postoperative recovery and the need for analgesia. In this study, we evaluated the effect of listening to music under general anesthesia on the neurohormonal response to surgical stress as measured by epinephrine, norepinephrine, cortisol, and adrenocorticotropic hormone (ACTH) blood levels. Thirty female patients scheduled for abdominal gynecological procedures were enrolled and randomly divided into two groups: group NM (no music) and group M (music). In group M, music was played from after the induction of anesthesia until the end of surgery. In the NM group, the patients wore the headphones but no music was played. We established three sample times for hormonal dosage during the procedure and one in the recovery room. Hemodynamic data were recorded at all times, and postoperative consumption of morphine in the first 24 h was noted. There was no group difference at any sample time or in the postoperative period in terms of mean arterial blood pressure, heart rate, isoflurane end-tidal concentration, time of the day at which the surgery was performed, bispectral index (BIS) value, doses of fentanyl, or consumption of postoperative morphine. There was no difference between the two groups with regard to plasmatic levels of norepinephrine, epinephrine, cortisol, or ACTH at any sample time, although the blood level of these hormones significantly increased in each group with surgical stimulation. In conclusion, we could not demonstrate a significant effect of intraoperative music on surgical stress when used under general anesthesia. IMPLICATIONS: Listening to music under general anesthesia did not reduce perioperative stress hormone release or opioid consumption in patients undergoing gynecological surgery.

Adolescent↗

PubMed2004

Signature of a silent killer: expression profiling in epithelial ovarian cancer.

With the sequencing of the human genome and the simultaneous development of high-throughput strategies, cancer biologists have entered an exciting new area for gene expression analysis, with the ability to glimpse higher order patterns of genetic and epigenetic alterations in complex diseases. Ovarian cancer biologists are rising to the challenge of applying these new technologies to this silent killer, with the eventual goal of improving the quality of life and long-term survival of patients. This review provides a summary of the disease, a description of available technologies and their application to the ovarian cancer problem, as well as a discussion on the challenges and opportunities related to DNA microarray expression profiling-based research, including downstream clinical applications.

Biomarkers, Tumor↗

PubMed2004

Use of hormonal replacement therapy after treatment of breast cancer.

OBJECTIVE: To review the use of hormonal replacement therapy (HRT) after treatment of breast cancer. OPTIONS: The effect and role of estrogens on breast cancer. OUTCOME: Improved health and quality of life for women with breast cancer. VALUES: References were collected through MEDLINE searches up to 2002. EVIDENCE: The level of evidence and quality of recommendations have been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS, AND COSTS: Utilization of the information to make a proper risk-benefit assessment of HRT use in women with breast cancer. RECOMMENDATIONS: 1. HRT after treatment of breast cancer has not been demonstrated to have an adverse impact on recurrence and mortality.(II-2B) 2. HRT is an option in postmenopausal women with previously treated breast cancer.(II-2B) 3. Prospective, randomized clinical trial results are needed.(III-A) VALIDATION: Recommendations were reviewed and revised by the Breast Disease Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the Executive and Council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

Breast Neoplasms↗

PubMed2003

Patterns of expression of chromosome 17 genes in primary cultures of normal ovarian surface epithelia and epithelial ovarian cancer cell lines.

Oligonucleotide microarray analysis was applied to assess the expression profile of 332 probe sets representing 308 genes or expressed sequence tags (ESTs) that map to chromosome 17 in order to address epigenetic events that result in alterations in gene expression in epithelial ovarian cancer (EOC). Expression profiles were generated from 12 primary cultures derived from normal ovarian surface epithelium (NOSE) and four long-term cultures (TOV-81D, TOV-112D, TOV-21G and OV-90) derived from EOCs that have been previously characterized and shown to mimic features of the tumoral cells from which they were derived. The expression values of all 332 probe sets is highly correlated across the 12 NOSEs (89% correlation coefficients >0.90). In two-way comparisons, differential patterns of gene expression were observed for 157 probe sets for which the expression value of at least one EOC cell line fell outside the limits of the range of expression of the 12 NOSEs. When compared to NOSEs, four genes displayed similar differential patterns of gene expression across all four EOC cell lines, and 26 genes displayed similar differential patterns of gene expression across the three EOC cell lines (TOV-112D, TOV-21G and OV-90) representing tumoral cells derived from the most aggressive disease. A total of 17 genes displayed differential patterns of gene expression greater than threefold in at least one EOC cell line in comparison to NOSE, and three genes were differentially expressed greater than threefold across all aggressive cell lines. The analysis of a selected number of genes by RT-PCR revealed patterns of gene expression comparable to those observed by microarray analysis in the majority of samples tested. Comparison of expression profiles of differentially expressed genes identified by microarray analysis in two-way comparisons of the EOC cell lines and the NOSEs with published reports revealed 10 genes previously implicated in ovarian tumorigenesis and 18 in tumorigenesis of other types of cancer. The differential pattern of gene expression of genes that map to both the p and q arm of chromosome 17 is consistent with the hypothesis that a number of genes that map to this chromosome are implicated in the etiology of ovarian cancer.

Cells, Cultured↗

PubMed2003

Herpes simplex virus type II is not a cofactor to human papillomavirus in cancer of the uterine cervix.

OBJECTIVE: Cells that were cotransfected with herpes simplex virus-16 and the herpes simplex virus type 2 Xho -2 DNA induce tumors in nude mice. In a cross-sectional study, we investigated the role of herpes simplex virus type 2 as a cofactor to human papillomavirus in cervical cancer. STUDY DESIGN: Cervical cells that were obtained with an endocervical Cytobrush brush (Medscand) from 439 women (50 women with cancer lesions, 65 women with high-grade squamous intraepithelial lesions, 80 women with low-grade squamous intraepithelial lesions, 244 healthy subjects) and DNA that was extracted from 150 cervical cancer biopsy specimens were analyzed with polymerase chain reaction for herpes simplex virus type 2 Xho -2 and Bgl IIC transforming DNA sequences. RESULTS: All 439 cervical samples and 150 cervical cancer biopsy specimens tested negative for herpes simplex virus type 2 Xho -2 and Bgl IIC DNA by polymerase chain reaction. Overall, none of 200 samples (0%) from women with invasive cervical cancer contained herpes simplex virus type 2 Xho -2 or Bgl IIC DNA (95% CI, 0.0-1.8). CONCLUSION: Although herpes simplex virus type 2 Bgl IIN transforms epithelial cells in vitro, it was not detected in cervical cancer specimens.

Adenocarcinoma↗

PubMed2002

Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. METHODS: We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. RESULTS: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCA1 mutation carriers, ever use of oral contraceptives was associated with a modestly increased risk of breast cancer (OR = 1.20, 95% CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95% CI = 1.17 to 1.75). CONCLUSIONS: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.

Adolescent↗

PubMed2002

Detection of human herpes virus type 6 DNA in precancerous lesions of the uterine cervix.

Human herpes virus type 6 (HHV-6) DNA has been suggested to be a cofactor to human papillomavirus (HPV) in cervical cancer. In a cross-sectional study, we investigated the association between HHV-6 DNA detected in cervical brushings and high-grade squamous intraepithelial lesions (HSIL), while controlling for genital infection with 27 genotypes of HPV. Of the 320 women recruited from an oncologic gynecology clinic, 50 had invasive cervical cancer, 65 had HSIL, 80 had low-grade squamous intraepithelial lesions (LSIL), and 125 were normal. Four of the seven HHV-6-positive women had HSIL. HHV-6 was associated with HSIL after adjusting for age and socioeconomic status (odds ratio [OR] of 10.9, 95% confidence interval [CI]: 1.1-107.1). This association was no longer significant after controlling for HPV (OR = 6.4, 95% CI = 0.3-128.5). HHV-6 was detected in cervical samples from women with precancerous and cancerous lesions of the cervix, but not significantly more frequently than in normal women.

Adolescent↗