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.

Sociodemographic characteristics and perinatal mortality among singletons in North East Tanzania: a registry-based study.

OBJECTIVES: Sub-Saharan Africa has the highest known perinatal mortality rates in the World, but few studies have assessed the importance of parental sociodemographic characteristics on perinatal mortality in this region. The aim of this study was to estimate how sociodemographic patterns affect perinatal mortality in Northern Tanzania. DESIGN AND SETTINGS: A registry-based study using births from 1999 to 2006 at a hospital in North Eastern Tanzania. PARTICIPANTS AND METHODS: 14 394 singleton births with birthweight 500 g or higher and a known perinatal survival status. Births of women with residence outside the local district who were referred to the hospital for delivery for medical reasons were excluded. RESULTS: Perinatal mortality was 41.1 per 1000 births. Factors independently associated with higher perinatal mortality were: higher paternal age (> 45) compared to age 26-35 (adjusted relative risk (ARR) 2.0; 95% CI 1.4 to 2.8), low paternal education (only primary) compared to secondary or higher (ARR 1.3; 95% CI 1.1 to 1.7), paternal ethnicity other than Chagga or Pare (ARR 1.4; 95% CI 1.1 to 1.7), paternal farming occupation (ARR 1.5; 95% CI 1.1 to 2.2), maternal service occupation (ARR 1.7; 95% CI 1.2 to 2.6), maternal height 150 cm or lower (ARR 1.4; 95% CI 1.0 to 1.8) and residence in the rural or semi-urban area (ARR 1.4; 95% CI 1.1 to 1.7). CONCLUSIONS: There are strong sociodemographic gradients in perinatal mortality in Africa. Paternal social characteristics appear to have stronger influence on perinatal mortality than maternal characteristics. This may reflect social and cultural conditions that need to be considered by policymakers in developing countries.

Maternal HIV status and pregnancy outcomes in northeastern Tanzania: a registry-based study.

OBJECTIVES: The proportion of women delivering with known HIV status in sub-Saharan Africa is not well described. Risk of HIV transmission to newborns is a major concern, but there may also be increased risks for other adverse pregnancy outcomes. DESIGN: Hospital registry. SETTING: North East Tanzania (1999-2006). POPULATION: Singletons (n = 14,444). METHODS: Births were grouped by maternal HIV status and socio-demographic factors predicting HIV status, and associations between status and pregnancy outcomes were studied. MAIN OUTCOME MEASURES: Maternal HIV status, perinatal mortality, prematurity, small for gestational age (SGA), birthweight and low Apgar score. RESULTS: The proportion of mothers with known HIV status increased from 7% before 2001 to 78% after 2004. Single motherhood, rural residence, low maternal education, maternal and paternal farming and higher paternal age were associated with unknown HIV status. About 7.4% (95% CI 6.7-8.1%) of women were HIV infected, with increased likelihood of infection with higher gravidity, single motherhood, rural residence, maternal business or farming occupations and paternal tribe. Compared with HIV-uninfected women, the untreated HIV-infected women had a higher risk of SGA births (adjusted risk ratio [ARR] 1.6; 95% CI 1.1-2.4), preterm birth (ARR 1.8; 95% CI 1.1-2.7) and perinatal death (ARR 1.9; 95% CI 0.95-3.8). Women with unknown HIV status had moderately increased risks. Treated HIV-infected women had a risk similar to that of the HIV-uninfected women for all outcomes, except for low Apgar score. CONCLUSION: HIV testing and infection were associated with socio-demographic factors. Untreated HIV-infected women had higher risks of adverse pregnancy outcomes, and risks were also increased for women with unknown HIV status. There is still a need to increase availability of HIV testing, education and adequate therapy for pregnant women.

Child sexual abuse in Matabeleland, Zimbabwe.

The extent, nature, causes and consequences of child sexual abuse in Matabeleland. Zimbabwe, are explored by an intersectoral working group consisting of health, legal and AIDS prevention workers who were struck in the course of their work by the regularity with which they saw sexually abused children infected with HIV and STDs. Methods used in this study are record review, focus group discussions, structured and in-depth interviews. Child sexual abuse cases form between 40-60% of the rape cases brought to the attention of hospitals, police and court and many more are believed to remain unreported. Half of the sexual abuse in children is detected through STDs and some have HIV. The majority of offenders are mature men known to the child. Factors influencing child sexual abuse are male dominance in society, men's professed inability to control sexual desire, and magic beliefs. Victims are traumatized by the abuse itself as well as by subsequent problems in family, health and in court. Since child sexual abuse may endanger the life and well-being of the child, it is a serious problem that requires urgent action.