PEG1/MEST and IGF2 DNA methylation un CIN and in cervical cancer

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk (AU)

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PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer.

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.

[Gestational diabetes in East Africa: a mostly disregarded disease?]. / Schwangerschaftsdiabetes in Ostafrika: eine Erkrankung, die zu wenig Beachtung findet?

The majority of all deliveries worldwide take place in the so-called developing world. Most recent epidemiological data have shown that the number of cases of type 2 diabetes mellitus and diabetes in pregnancy is steadily increasing worldwide. However, little is known about the prevalence of gestational diabetes in East Africa. Intrauterine exposure to the metabolic environment of maternal diabetes increases the risk of altered glucose homeostasis in the offspring, producing a higher prevalence of gestational diabetes mellitus in the next generation. Our preliminary results from an East African tertiary referral center show that in the year 2007 3.1% of all newborns had a birth weight of more than 4,000 g (mean 4,300 g, range 4,000- 5,600 g). During the same time period, the mean birth weight in the general population was only 3,046 g (range 600-3,200 g). Hence, personal experience in East Africa has convinced the authors that diabetes in pregnancy is grossly neglected. Besides infectious diseases like HIV/AIDS, the African continent is increasingly facing metabolic diseases such as type 2 diabetes mellitus and diabetes in pregnancy.

Prevalence and severity of cervical squamous intraepithelial lesion in a tertiary hospital in northern Tanzania.

Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer deaths in Tanzanian women. Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming reports associating SIL and HIV infection, however in Tanzania such reports are limited. A cross-sectional hospital-based descriptive study was conducted to determine the prevalence and severity of SIL in 234 HIV seropositive and seronegative women aged 18-68 years old at Kilimanjaro Christian Medical Centre in northern Tanzania. A structured questionnaire was used to collect sociodemographic data. In addition, blood was collected for rapid HIV antibody testing and CD4+ T-lymphocyte counts to associate with prevalence and severity of SIL from the cervical smear collections. A total of 214 subjects had smear results regarded as valid for interpretation, of which 46.3% were HIV seropositive. Overall rate of SIL was 17%. Proportion of SIL among HIV seropositive subjects was 32% versus 4% in seronegative subjects (OR = 13.3, 95% CI = 4.2-46.4). Low CD4+ T-lymphocyte cell count was associated with higher prevalence of SIL (P = 0.001). The relationship between CD4+ T-lymphocyte cell counts and the severity of cervical SIL was significant (P = 0.007). Marital status and number of lifetime sex partners were risk factors significantly associated with SIL (P = 0.004 and 0.005, respectively). SIL was not associated with age, education level, parity or age at sex debut. The prevalence and severity of cervical SIL was significantly associated with HIV infection and immunologic disease progression. These findings underscore the need for HIV screening among women with SIL, and the need for cervical cancer screening in HIV-infected women. Marital status and number of lifetime sex partners were significant risk factors associated with SIL.