Associations between methylation of paternally expressed gene 3 (PEG3), cervical intraepithelial neoplasia and invasive cervical cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress.

Dietary patterns and breast cancer risk among women in northern Tanzania: a case-control study.

BACKGROUND: Breast cancer is the second most common cancer among women in the Kilimanjaro Region of Tanzania. It was tested within a case-control study in this region whether a specific dietary pattern impacts on the breast cancer risk. METHODS: A validated semi-quantitative Food Frequency Questionnaire was used to assess the dietary intake of 115 female breast cancer patients and 230 healthy age-matched women living in the same districts. A logistic regression was performed to estimate breast cancer risk. Dietary patterns were obtained using principal component analysis with Varimax rotation. RESULTS: The adjusted logistic regression estimated an increased risk for a "Fatty Diet", characterized by a higher consumption of milk, vegetable oils and fats, butter, lard and red meat (OR = 1.42, 95 % CI 1.08-1.87; P = 0.01), and for a "Fruity Diet", characterized by a higher consumption of fish, mango, papaya, avocado and watery fruits (OR = 1.61, 95 % CI 1.14-2.28; P = 0.01). Both diets showed an inverse association with the ratio between polyunsaturated and saturated fatty acids (P/S ratio). CONCLUSION: A diet characterized by a low P/S ratio seems to be more important for the development of breast cancer than total fat intake.

Breast cancer risk among women with long-standing lactation and reproductive parameters at low risk level: a case-control study in Northern Tanzania.

Breast cancer is the leading cause of death among women worldwide. Studies in industrialised countries identified age at menarche, age at first full-term pregnancy, and lactation as determining factors in the aetiology of breast cancer. 115 female breast cancer patients (cases) and 230 age- and district-matched women clinically free from breast cancer (controls) were interviewed about their reproductive history and socioeconomic condition. Semi-structured interviews including anthropometric measurements were conducted by trained enumerators. The median age was 50 years (min/max 26 to 85 years). Estimated median BMI at age 20 was 21 kg/m(2) in both cases and controls. Median lifelong lactation of the mothers was 96 months (cases) and 108 months (controls). A high BMI at 20 years was associated with an increased breast cancer risk (OR 1.31 95% CI 1.11-1.55, P < 0.01). The odds ratio for lifelong lactation was slightly below one (OR 0.99 95% CI 0.98-1.00, P < 0.01). There was no significant association in risk for BMI at interview (median 25 kg/m(2) of cases and 26 kg/m(2) of controls), age at menarche (median 16 years), and age at first full-term pregnancy (median 20 years). The association of increased risk with higher BMI at age 20 years remained significant after stratification for menopause (premenopausal: OR 1.41 95% CI 1.10-1.81, P = 0.01; postmenopausal: OR 1.38 95% CI 1.06-1.80, P = 0.02). Late age at menarche and prolonged lifelong lactation were associated with a risk reduction among premenopausal women (ORmenarche 0.74 95% CI 0.56-1.00, P = 0.05; ORlactation 0.98 95% CI 0.97-0.99, P < 0.01). In conclusion, long-standing lactation and reproductive behaviour are associated with a lower breast cancer risk in the region. As current changes in lifestyle affect age at menarche, reproductive behaviour, and nutritional status, an increased incidence of breast cancer is to be expected. Preventive efforts should include advice on reproductive and breastfeeding behaviour.

Clinical factors associated with malignancy and HIV status in patients with ocular surface squamous neoplasia at Kilimanjaro Christian Medical Centre, Tanzania.

AIMS: To describe the clinical characteristics of ocular surface squamous neoplasia (OSSN) in a sub-Saharan referral hospital setting according to histopathological diagnosis and HIV status. METHODS: All patients were enrolled who presented consecutively to the Kilimanjaro Christian Medical College eye department with lesions suspected to be OSSN from September 2005 to May 2007 and from February 2008 to September 2008. Clinical characteristics were documented on a standardised form, excision biopsies were performed and histopathological diagnosis was obtained on all cases. Data were analysed to look for associations among various factors. RESULTS: 150 patients were enrolled. Histopathological study showed OSSN in 88% of cases. Of these, 128 (85.6%) were under the age of 50 years and 60% were HIV positive. The median CD4 cell count was 71 cells/µl among HIV-positive cases. Independent of size, the lesions of patients who were HIV positive were more likely to be higher grade malignancy than those who were HIV negative. CONCLUSION: In a sub-Saharan setting, OSSN occurs in persons who are younger than in industrialised countries and is often associated with HIV positivity. CD4 cell counts indicate that a majority of HIV-positive patients with OSSN are significantly immunosuppressed at presentation. Higher grade malignancy in this group could indicate a more aggressive course.

Invasive disease caused by nontuberculous mycobacteria, Tanzania.

Data on nontuberculous mycobacterial (NTM) disease in sub-Saharan Africa are limited. During 2006-2008, we identified 3 HIV-infected patients in northern Tanzania who had invasive NTM; 2 were infected with "Mycobacterium sherrisii" and 1 with M. avium complex sequevar MAC-D. Invasive NTM disease is present in HIV-infected patients in sub-Saharan Africa.

Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania.

BACKGROUND: Schistosomiasis affects the reproductive health of women. Described sequelae are ectopic pregnancy, infertility, abortion, and cervical lesions and symptoms mimicking cervical cancer and STIs. There are indications that cervical schistosomiasis lesions could become co-factors for viral infection such as HIV and HPV. METHODS: In a retrospective descriptive histopathological study clinical specimens sent between 1999 and 2005 to the pathology department of a consultant hospital in Tanzania were reviewed to analyse the occurrence and features of schistosomiasis in female genital organs. RESULTS: During the study period, schistosomiasis was histopathologically diagnosed in 423 specimens from different organs (0.7% of all specimens examined in the study period), out of those 40% were specimens from female and male organs. The specimens were sent from 24 hospitals in 13 regions of mainland Tanzania. Female genital schistosomiasis was diagnosed in 125 specimens from 111 patients. The main symptoms reported were bleeding disorders (48%), ulcer (17%), tumor (20%), lower abdominal pain (11%) and infertility (7%). The majority of cases with genital schistosomiasis were diagnosed in cervical tissue (71 cases). The confirmation of cervical cancer was specifically requested for 53 women, but the diagnosis could only be verified for 13 patients (25%), in 40 cases only severe cervical schistosomiasis was diagnosed. Vulval/labial schistosomiasis was seen in specimens from young women. Infertility was reported in four patients with schistosomiasis of the Fallopian tubes. CONCLUSION: Genital schistosomiasis adds to the disease burden of women in all age groups. Pathological consequences due to the involvement of different genital organs can be damaging for the affected women. Clinical unawareness of genital schistosomiasis can lead to misdiagnosis and therefore false and ineffective therapy. In endemic areas cervical schistosomiasis should be considered as differential diagnosis of cancer.