Association between endometriosis and polymorphisms in insulin-like growth factor binding protein genes in Korean women

Objective

Genetic factors are known to be associated with the development and progression of endometriosis, but the genes related to endometriosis have not been defined. Insulin-like growth factor binding proteins (IGFBPs) are believed to be involved in the proliferation and apoptosis of cells that play an important role in the pathophysiologic mechanism of endometriosis. This study aimed to determine the association between endometriosis and polymorphisms of the IGFBP genes in Korean women.

Study design

In a case–control study, the rs1995051, rs1065780 and c.759A > G single nucleotide polymorphisms (SNPs) in the IGFBP1 gene and the −672A > G, −202A > C and c.95C > G SNPs in the IGFBP3 gene were analyzed in 128 women with endometriosis and 108 normal control women.

Results

The haplotype genotype composed of a combination of three IGFBP1 gene polymorphisms was not related to endometriosis, while the haplotype genotype of the IGFBP3 gene had a significant association with endometriosis. Women not carrying the AAG (−672A/−202A/c.95G) haplotype allele of three IGFBP3 gene polymorphisms have a 3.19-times higher risk of endometriosis compared with women with AAG homozygotes, and this trend was found in women with advanced endometriosis but not in women with early endometriosis.

Conclusions

The AAG haplotype allele of the −672A > G, −202A > C and c.95C > G polymorphisms in the IGFBP3 gene may be associated with advanced endometriosis in Korean women.     

Interleukin-1 beta gene polymorphisms and preterm birth

Objective

To investigate the association between two genetic variations in the Interleukin-1 beta (IL1B) gene and preterm birth.

Study design

In this case-control study we tested the allelic distribution of two of its common polymorphisms (IL1B +3953C>T [rs1143634], IL1B −511C>T [rs16944]) in one hundred women with preterm birth and one hundred healthy women with at least one uncomplicated full term pregnancy and no history of preterm birth.

Results

A significant association was found between the presence of the IL1B +3953C>T polymorphism and preterm birth (p = 0.049, OR 0.6 [0.3–1.0]). No significant association was found between the IL1B −511C>T polymorphism and preterm birth (p = 0.471, OR 1.3 [0.7–2.3]).

Conclusion

Our findings suggest that the IL1B +3953C>T polymorphism is associated with a risk reduction for preterm birth in Caucasian women, possibly by altering the inflammatory response during pregnancy.     

Younger age distribution of cervical cancer incidence among survivors of pediatric and young adult cancers

Background

Pediatric and young adult (PAYA) cancer survivors may have an earlier onset of chronic diseases compared with the general population. We compared the age at cervical cancer diagnosis between PAYA cancer survivors and females in the general US population.

Methods

We used longitudinal data from 9 population-based registries of the Surveillance, Epidemiology, and End Results program collected between 1973 and 2010. PAYA cancer survivors were females diagnosed with any cancer before age 30 years, survived at least 5 years post-diagnosis, and were subsequently diagnosed with invasive cervical cancer (n = 46). The general US population comprised females who were diagnosed with invasive cervical cancer as the primary malignancy (n = 26,956). We estimated the difference in median age at diagnosis (ß₅₀) and bootstrap 95% confidence limits (CL) of invasive cervical cancer after adjustment for year of diagnosis and race.

Results

The median age at diagnosis of invasive cervical cancer was 33 years for female PAYA cancer survivors and 40 years for females in the general US population (ß₅₀ = − 7.0, 95% CL: − 11, − 3.2). Similar differences were observed across subgroups of stage and histologic subtype of invasive cervical cancer.

Conclusion

Our results suggest that PAYA cancer survivors are diagnosed with invasive cervical cancer at a substantially younger age compared with females without a prior cancer diagnosis in the general US population. This issue warrants further study, and could have implications for determining age at initiation or frequency of cervical cancer screening if younger age at diagnosis is attributable to an underlying biological phenomenon.     

Genetic variations of interleukin-1 and -6 genes and risk of cervical intraepithelial neoplasia

Objective

To evaluate the association between five interleukin-1 (IL-1) and -6 gene polymorphisms and risk of high grade cervical intraepithelial neoplasia (CIN 2-3).

Methods

This case-control study investigates five common IL-1 and IL-6 gene polymorphisms in 131 women with CIN 2-3 and 209 controls by pyrosequencing and polymerase chain reaction. Associations between gene polymorphisms and risk of CIN 2-3 are analysed by univariate and multivariable models. Their combined effect on the risk of CIN is evaluated by haplotype analysis.

Results

In a multivariable regression model IL1A −889 (odds ratio 0.3 [95% confidence interval 0.1-0.8], p = 0.01) and smoking (4.0 [1.7-9.1], p = 0.001) are independently associated with the risk of high grade CIN. Haplotype analysis does not reveal any high-risk combinations for the susceptibility of CIN.

Conclusion

The single nucleotide polymorphism IL1A −889 is independently associated with risk of high grade CIN.     

A genetic variant in pre-miR-27a is associated with a reduced cervical cancer risk in southern Chinese women

Objective

MicroRNAs (miRNAs) play critical roles in cervical carcinogenesis. Common single nucleotide polymorphisms (SNPs) in pre/pri-miRNAs may change their property through altering miRNAs expression and/or maturation. Here we aimed to investigate the influence of three common SNPs in pre/pri-miRNAs (pri-miR-26a-1 rs7372209, pre-miR-27a rs895819 and pri-miR-100 rs1834306) on individual susceptibility to cervical cancer.

Methods

We genotyped these three polymorphisms in 103 cervical cancer cases and 417 cancer-free female subjects using polymerase chain reaction–ligation detection reaction (PCR–LDR) method. Unconditional logistic regression analysis was utilized to estimate the association between these polymorphisms and the risk of cervical cancer.

Results

In a logistic regression analysis, we found that the rs895819 polymorphism in pre-miR-27a exhibited a significant effect on cervical cancer risk; T allele (OR = 0.68, 95% CI = 0.49–0.95, P = 0.025), and CT (OR = 0.33, 95% CI = 0.15–0.74, P = 0.007) or TT (OR = 0.33, 95% CI = 0.15–0.72, P = 0.006) genotype were associated with the decreased risk, compared to C and CC respectively. As we used further genotype association models, we found a similar trend of the association in additive (OR = 0.70, P = 0.041) and recessive model (OR = 0.33, P = 0.004). We did not detect any association of the other two SNPs in pri-miR-26a-1 (rs7372209) and pri-miR-100 (rs1834306) with cervical cancer risk.

Conclusion

Our study provides the first evidence that the miR-27a rs895819 polymorphism is associated with a decreased risk of cervical cancer in southern Chinese women.     

Polymorphisms in immune mediators associate with risk of cervical cancer

Objective

The immune system is critical for controlling the progression of HPV cervical disease and the development of cancer. This study aimed to identify cervical cancer susceptibility alleles in candidate immune-modulating genes.

Methods

Our family-based study involved a cohort of 641 probands (women with ICC/CIN III) and their biologic parents or siblings (641 trios). In the discovery phase (stage 1), involving 288 of the trios, 80 tag single nucleotide polymorphisms (SNPs) in 11 immune-modulating genes (IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1, STAT6, IL12A, TNF, LTA and LTB) were evaluated on the GoldenGate platform. We used the combined dataset for a total of 641 trios (stage 2) and the Taqman platform to validate the SNPs that had proved significant in the discovery dataset. The transmission disequilibrium test was used to detect significant shifts in allelic transmissions in the datasets.

Results

Two SNPs in JAK2 and one SNP in STAT6 showed significant allelic association with cervical cancer in the stage 1 discovery dataset and were replicated in the larger joint analysis stage 2 dataset (JAK2 rs10815144, P = 0.0029 and rs12349785, P = 0.0058; and STAT6 rs3024971, P = 0.0127). An additional SNP in exon 19 of JAK2 (rs2230724) was also examined in the combined dataset due to its strong linkage disequilibrium (LD) with rs10815144. It was also significant (P = 0.0335).

Conclusions

Our results suggest an association of SNPs in JAK2 and STAT6 with cervical cancer. This association should be investigated in additional cervical cancer populations.     

Vascular endothelial growth factor gene polymorphisms in Korean patients with premature ovarian failure

Objective

To study the association of vascular endothelial growth factor (VEGF) polymorphisms (−2578C>A, −1154G>A, −634G>C, and 936C>T) with premature ovarian failure (POF) in Korean patients.

Study design

Prospective case-control study. One hundred and thirty five patients with POF and confirmed serum follicle-stimulating hormone levels of >40 IU/L before the age of 40 years and 120 healthy controls with at least one live birth, regular menstrual cycles, and karyotype 46, XX.

Results

POF patients exhibited significantly different frequencies of the VEGF −1154GA genotype (odds ratio [OR], 2.002; 95% confidence interval [CI], 1.116-3.592; P = 0.019), and −2578CA+AA/−1154GA+AA combination genotype (OR, 1.805; 95% CI, 1.013-3.217; P = 0.044) compared to the control group. The frequency of the −2578A/−1154A haplotype (OR, 1.647; 95% CI, 1.017-2.677; P = 0.041) was significantly higher in the POF group than in the control group.

Conclusion

The VEGF −1154G>A mutation, −2578CA+AA/−1154GA+AA combination genotype, and −2578A/−1154A haplotype are significantly associated with POF in Korean women.     

The association of IL-1β, IL-2, and IL-6 gene polymorphisms with bone mineral density and osteoporosis in postmenopausal women

Objective

Osteoporosis is a common disorder with a strong genetic component. The genetics of osteoporosis impacts on the prediction, diagnosis, prognosis, and treatment of the disease.

Study design

The aim of the present study was to examine associations between cytokine gene polymorphisms (IL-1β, IL-2, IL-6) and bone mineral density (BMD) values in postmenopausal women.The study included 226 postmenopausal women with a diagnosed BMD T-score lower than −2.5 SD (mean: −3.02 ± .053) and 224 postmenopausal women with a BMD T-score greater than −2.5 SD (mean: −1.33 ± 0.51).

Results

Among the women with T-scores below −2.5 SD, the BMD values were significantly lower in the carriers of the IL-6 GG genotype compared with those with the CC and GC genotypes (0.70 ± 0.38 vs. 0.73 ± 0.25 and 0.74 ± 0.23 for the lumbar spine, 0.54 ± 0.18 vs. 0.56 ± 0.15 and 0.58 ± 0.22 for the femoral neck). There were no statistically significant associations between the IL-1β and IL-2 genotypes and BMD values in the group of women with T-scores below −2.5 SD.

Conclusion

The results of the present study suggest an association of the IL-6 −174 G/C polymorphism with osteoporosis in postmenopausal women.     

Polymorphisms of FAS and FAS ligand genes in preeclamptic women

Objectives

This study investigated the influence that Fas and Fas ligand gene polymorphisms might have on preeclampsia. The pathogenesis of preeclampsia is still enigmatic and several studies have proposed that it may, in part, be determined by genetic susceptibility. Therefore, the identification of a gene polymorphism associated with an increased risk of preeclampsia might well represent a useful tool in the identification of at risk pregnant women enabling the setup of preventive therapy.Apoptosis has also been implied in the pathogenesis of preeclampsia and since Fas and Fas ligand are the main apoptotic pathway members, they may represent candidate genes involved in the development of preeclampsia.A polymorphism at the 670 position (A–G) in the Fas gene has been found more frequently in Hungarian women with preeclampsia.

Study design

The study cohort was a group of 50 women with preeclampsia and 142 healthy control subjects from the general Italian population. They were studied, by RFLP analysis, to validate the role that the 670 G Fas gene polymorphism plays in preeclampsia, and to evaluate the Fas ligand IVS2nt 124 G polymorphism. The Fisher's exact test was used to compute the statistical difference between groups.

Results

The presence of the 670 G Fas gene variant was observed in 42 preeclamptic patients (84%) and 96 members of the general population control group (67.6%) (p = 0.029). Regarding the Fas ligand gene, the IVS2nt 124 G variant was present in 14 preeclamptic patients (28%) and in 47 of the general population control subjects (33.1%) (p = 0.6).

Conclusions

The present study validated the hypothesis that the Fas 670 G variant may have an influencing role in preeclampsia.     

Campaña de lucha contra el cáncer de cuello uterino en Guinea-Bissau. Estudio de las citologías de un trimestre

Objective

To study 300 cytologies from a single trimester, within a campaign against uterine cervical cancer in Guinea-Bissau.

Design

We compared 300 cytologies from Guinea-Bissau with 880 cytologies performed in a single month in autochthonous women attending our hospital for vaginal infections and cervical lesions.

Results

Significant differences between women in Guinea-Bissau and autochthonous women were found in Trichomonal infection (2% versus 0,34%, respectively; P < .001) and in low-grade squamous intraepithelial lesions (2% versus 0,68%, respectively; P = .05). One case of cervical cancer was detected in a 75-year-old multiparous woman. The mean number of deceased children in these women was 2 (range 1-8).

Conclusions

To avoid both cervical cancer and neonatal mortality, a permanent program for the early detection of cervical cancer in Guinea-Bissau is clearly needed, together with family planning, prenatal care and obstetric assistance.     

Genetic variations in EGFR and ERBB4 increase susceptibility to cervical cancer

Objectives

Inherited genetic variability contributes to susceptibility to cervical cancer. We investigated the association of single nucleotide polymorphisms (SNPs) in the human epidermal growth factor receptor (ERBB) family with cervical cancer.

Methods

We used the transmission disequilibrium test (TDT) to look for excessive transmission of tag single nucleotide polymorphisms (tSNPs) in ERBB family members EGFR, ERBB2, ERBB3, and ERBB4 in a large sample of women with invasive and in situ cervical cancer and their biological parents (628 trios). The study used a discovery set of trios (244) analyzed by Illumina GoldenGate in which SNPs reaching a P < .05 were re-tested by TaqMan in the combined set of 628. We also explored collaborative effects of different ERBB alleles.

Results

Based on single SNP TDT tests we identified 16 significant SNPs in the discover stage and six of 14 SNPs that could be assayed by TaqMan were significantly overtransmitted in women with cervical cancer in the combined replication set. Four SNPs were located in intron 1 of EGFR and two SNPs in intron 24 of ERBB4. The EGFR variants are located near multiple enhancers, silencers, and the previously identified functional common polymorphisms in intron 1.

Conclusions

Our data provide evidence for the involvement of intron 1 EGFR variants and intron 24 ERBB4 variants in modulating risk for the development of in situ and invasive cervical cancer. These variants should be examined in additional populations and functional studies would be needed to confirm this hypothesis.     

Distribution of human papillomavirus genotypes in women with cervical cancer in Slovenia

Objective

The purpose of the present study was to establish the distribution of human papillomavirus (HPV) genotypes in a representative population of women with cervical cancer in Slovenia in order to contribute to the lacking data on HPV in cervical cancer and to assess the potential local benefit of future prophylactic HPV vaccination.

Study design

A total of 284 samples of cervical cancer were analyzed including archival samples, cervical scrapes and fresh tissue samples. Polymerase chain reaction with GP5+/GP6+ primers was performed in all samples for HPV deoxyribonucleic acid (DNA) detection. All GP5+/GP6+ negative samples were additionally tested using CPI/CPIIg primers and INNO-LiPA HPV genotyping assay.

Results

After exclusion of 6 samples with unsuccessful amplification of beta-globin gene, 262 of 278 cervical cancer samples (94.2%) were HPV DNA positive. HPV genotypes found in the decreasing order of frequency were: HPV 16 (64.9%), HPV 18 (12.2%), HPV 33 (4.7%), HPV 45 (4.1%), followed by HPV 31, 51, 58, 59, 35, 52, 73 and 82 (3.5–0.2%). HPV positive samples were more frequent among squamous cell carcinomas than among adenocarcinomas/adenosquamous carcinomas (95.8% versus 85.5%; P = 0.003). HPV 16 was more frequently found in squamous cell carcinomas than in adenocarcinomas/adenosquamous carcinomas (69.9% versus 37.5%; P < 0.001), while the opposite was true for HPV 18 (6% versus 41.7%; P < 0.001).

Conclusion

Prophylactic HPV vaccination with currently available vaccines could prevent up to 77.1% of cervical cancer in Slovenia, which is caused by HPV 16 or HPV 18.     

The immunomodulatory effects of pegylated liposomal doxorubicin are amplified in BRCA1 − deficient ovarian tumors and can be exploited to improve treatment response in a mouse model

Objective

Women with BRCA-associated ovarian cancer demonstrate excellent responses to Pegylated Liposomal Doxorubicin (PLD). PLD has also been shown to enhance T cell recognition of tumor cells. Here we characterize immunophenotypic changes associated with BRCA1 dysfunction in ovarian cancer cells, and evaluate the T cell contribution to the therapeutic efficacy of PLD in a BRCA1 − ovarian cancer model to determine whether enhanced anti-tumor immunity contributes to the improved response to PLD in BRCA1 − ovarian cancers.

Methods

The immunophenotype of BRCA1 − and wild-type (WT) ovarian cancer cells and their response to PLD were compared in vitro using flow cytometry. T cell recruitment to BRCA1 − tumors was evaluated with flow cytometry and immunohistochemistry. The contribution of T cell populations to the therapeutic effect of PLD in a BRCA1 − model was evaluated using immunodepleting antibodies with PLD in vivo.

Results

The cytotoxic response to PLD was similar in BRCA1 − and WT cells in vitro. BRCA1 − inactivation resulted in higher expression of Fas and MHC-I at baseline and after PLD exposure. PLD prolonged the survival of BRCA1 − tumor bearing mice and increased intratumoral T cell recruitment. CD4 + depletion combined with PLD significantly prolonged overall survival (p = 0.0204) in BRCA1 − tumor-bearing mice.

Conclusion

Differences in the immunophenotype of BRCA1 − and WT cells are amplified by PLD exposure. The enhanced immunomodulatory effects of PLD in BRCA1 − tumors may be exploited therapeutically by eliminating suppressive CD4 + T cells. Our results support further study of combination therapy using PLD and immune agents, particularly in women with BRCA gene mutations.     

Vitamin D receptor Fok I polymorphism is associated with low bone mineral density in postmenopausal women: a meta-analysis focused on populations in Asian countries

Objective

To explore the associations between vitamin D receptor (VDR) gene polymorphisms (including Fok I, Bsm I and Apa I) and bone mineral density (BMD) in postmenopausal Asian women.

Study design

Databases of Medline, Embase and Wangfang were retrieved to identify eligible studies, with update to 1st February 2012. Standardized mean difference (SMD) and 95% confidence intervals were calculated by using fixed- or random-effect model. Best genetic comparison model was determined by using the Thakkinstian method.

Results

A total of 14 studies with 3243 healthy postmenopausal Asian women were included in this meta-analysis. Overall, pooled analyses indicated that the f allele of VDR Fok I was significantly associated with decreased BMD in the lumbar spine (ff vs. FF: SMD (95% CI): −0.87 (−1.38, −0.35); P = 0.001 for lumbar spine; −0.43 (−0.93, 0.06), P = 0.086 for femoral neck). In contrast, we did not observe overall associations between VDR Bsm I and Apa I polymorphisms and BMD in either lumbar spine or femoral neck (Bsm I bb vs. BB: SMD (95% CI): 0.61 (−1.30, 2.53), P = 0.531 for lumbar spine; Apa I aa vs. AA: SMD (95% CI): 0.66 (−0.16, 1.48), P = 0.113 for lumbar spine). When subgroup analyses were conducted according to countries, Indians carrying the VDR Fok I ff genotype were at risk of low BMD at lumbar spine (ff vs. FF: SMD (95% CI): −0.57 (−0.85, −0.29), P < 0.001). Sensitivity analyses indicated that no single study had substantial influence on all combined analyses. In addition, no publication bias was identified.

Conclusions

This meta-analysis indicated that VDR Fok I, rather than Bsm I and Apa I polymorphisms, is associated with bone mineral density in postmenopausal Asian women (especially for Indian women), and can probably be used with other genetic markers together to identify individuals at high risk of osteoporosis.     

Association of GSTP1 −313A/G polymorphisms and endometriosis risk: a meta-analysis of case–control studies

Objectives

In view of the controversies surrounding the association of glutathione S-transferases (GST) P1 with endometriosis, a meta-analysis of GSTP1 −313A/G polymorphism with endometriosis risk was performed.

Study design

The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct and Chinese Biomedical Literature Database (CBM) until March 2013. The association between GSTP1 −313A/G polymorphism and endometriosis risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95% CIs).

Results

A total of eight case–control studies were eventually identified. We found that GSTP1-313A/G polymorphism was not associated with endometriosis risk in the overall population (A vs. G: OR = 1.02, 95% CI = 0.97–1.07, P = 0.511; AA vs. GG: OR = 1.02, 95% CI = 0.98–1.06, P = 0.359; GA vs. GG: OR = 1.03, 95% CI = 0.98–1.08, P = 0.299; AA vs. GA/GG: OR = 1.01, 95% CI = 0.96–1.07, P = 0.621; AA/GA vs. GG: OR = 1.00, 95% CI = 0.97–1.03, P = 0.972). In the sub-group analysis based on ethnicity, a significant association was found in Caucasians under the recessive model (AA vs. GA/GG: OR = 1.28, 95% CI = 1.08–1.53, P = 0.006).

Conclusions

GSTP1 −313A/G polymorphism may not be associated with endometriosis risk, while the observed increase in risk of endometriosis may be due to small-study bias. Considering the limited sample size and ethnicity included in our meta-analysis, an updated meta-analysis will be urgently needed when further larger and well-designed studies are published.     

Methylation marker analysis and HPV16/18 genotyping in high-risk HPV positive self-sampled specimens to identify women with high grade CIN or cervical cancer

Objectives

Methylation marker analysis using bi-marker panel MAL/miR-124-2 is a promising triage test for identifying cervical (pre)cancer in high-risk human papillomavirus (hrHPV) positive women. Bi-marker panel MAL/miR-124-2 can be applied directly on self-sampled cervico-vaginal material and its sensitivity is non-inferior to that of cytology, yet at the cost of more colposcopy referrals. Our objective was to increase specificity of MAL/miR-124-2 methylation analysis by varying the assay thresholds and adding HPV16/18 genotyping.

Methods

1019 hrHPV-positive women were selected from a randomized controlled self-sampling trial (PROHTECT-3; 33–63 years, n = 46,001) and nine triage strategies with methylation testing of MAL/miR-124-2 and HPV16/18 genotyping were evaluated. The methylation assay threshold was set at four different predefined levels which correspond with clinical specificities for end-point cervical intra-epithelial grade 3 or worse (CIN3 +) of 50%, 60%, 70%, and 80%.

Results

The CIN3 + sensitivity of methylation analysis decreased (73.5 to 44.9%) while specificity increased (47.2 to 83.4%) when increasing the assay threshold. CIN3 + sensitivity and specificity of HPV16/18 genotyping were 68.0% and 65.6%, respectively. Combined methylation analysis at threshold-80 and HPV16/18 genotyping yielded similar CIN3 + sensitivity as that of methylation only at threshold-50 (77.6%) with an increased specificity (54.8%).

Conclusions

Combined triage by MAL/miR-124-2 methylation analysis with threshold-80 and HPV16/18 genotyping reaches high CIN3 + sensitivity with increased specificity to identify women with cervical (pre)cancer among HPV self-sample positive women. The combined strategy is attractive as it is fully molecular and identifies women at the highest risk of cervical (pre)cancer because of strongly elevated methylation levels and/or HPV16/18 positivity.     

Tumor necrosis factor α (−308), interleukin-6 (−174) and interleukin-10 (−1082) gene polymorphisms in polycystic ovary syndrome

Objective

The imbalance between pro- and anti-inflammatory cytokines and polymorphism of cytokine genes may play a role in the etiology of the polycystic ovary syndrome (PCOS). The aim of this study was to investigate the association of polymorphisms of TNFα, IL-6 and IL-10 genes with the occurrence and the clinical/laboratory characteristics of PCOS in the Turkish population.

Study design

Single nucleotide polymorphisms (SNPs) of TNFα (−308 G/A), IL-6 (−174 G/C), IL-10 (−1082 G/A) genes in DNA from peripheral blood leukocytes of 97 PCOS patients and 95 healthy control women were investigated.

Results

There is a tendency toward lower frequency of the IL-6 CC genotype and C allele among PCOS women compared with healthy controls although the difference did not reach a significant level. No notable differences were observed in allele or genotype frequencies for TNFα and IL-10 genes between groups. The concomitant presence of wild homozygous TNFα genotype together with mutant IL-6 C allele has a protective effect against PCOS with an OR = 0.45 (95% CI = 0.23–0.86). While TNFα (−308) and IL-10 (−1082) genotypes did not influence clinical/laboratory parameters in PCOS, IL-6 (−174) CC or pooled CG + CC genotypes have lower glucose, insulin, HOMA, cholesterol, triglyceride, and LDL-C, and higher GIR and HDL-C values than GG genotypes.

Conclusions

We suggest that the IL-6 promoter region polymorphism may be related to occurrence and metabolic abnormalities seen in PCOS in the Turkish population. However, more studies with larger sample size are necessary to support our findings in other populations before any statement can be made about the relationship between PCOS and cytokine polymorphism.     

Accuracy of dry vaginal self-sampling for detecting high-risk human papillomavirus infection in cervical cancer screening: A cross-sectional study

Objective

Cervical cancer screening coverage remains insufficient in most countries. Testing self-collected samples for high-risk human papillomavirus (HR-HPV) could be an alternative to the Pap smear, but costs, sampling methods and transport issues hamper its wide use. Our objective was to compare diagnostic accuracy of 2 vaginal self-collection methods, a dry swab (vsc-DRY) or swab in liquid medium (vsc-LIQ), for detecting HR-HPV cervical infection assessed by a cervical clinician-collected sample in liquid medium (ccc-LIQ).

Methods

Women 20 to 65 years attending a Pap smear were recruited between September, 2009 and March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were classified as HR-HPV + with detection of at least one HR-HPV or probable HR-HPV type.

Results

Of 734 women included, 722 had complete HPV data. HR-HPV was detected in 20.9% of ccc-LIQ samples. Estimated sensitivity and specificity to detect HR-HPV in vsc-DRY samples were 88.7% and 92.5%, respectively, and in vsc-LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were HR-HPV + in vsc-DRY, vsc-LIQ and ccc-LIQ samples. Among 6 samples of high-grade squamous intraepithelial lesions, all were HR-HPV + in vsc-DRY samples, 1 was HR-HPV − in vsc-LIQ samples and 1 was HR-HPV − in ccc-LIQ samples.

Conclusions

Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as compared with cervical clinician-collection and accurate as compared with cytology results. This cheap and easy-to-ship sampling method could be widely used in a cervical cancer screening program.