Estrogen receptor alpha gene polymorphism and endometrial cancer risk – a case-control study

Background: Estrogen is an established endometrial carcinogen. One of the most important mediators of estrogenic action is the estrogen receptor alpha. We have investigated whether polymorphic variation in the estrogen receptor alpha gene (ESR1) is associated with endometrial cancer risk. Methods: In 702 cases with invasive endometrial cancer and 1563 controls, we genotyped five markers in ESR1 and used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI). Results: We found an association between rs2234670, rs2234693, as well as rs9340799, markers in strong linkage disequilibrium (LD), and endometrial cancer risk. The association with rs9340799 was the strongest, OR 0.75 (CI 0.60–0.93) for heterozygous and OR 0.53 (CI 0.37–0.77) for homozygous rare compared to those homozygous for the most common allele. Haplotype models did not fit better to the data than single marker models. Conclusion: We found that intronic variation in ESR1 was associated with endometrial cancer risk

Reproductive factors and risk of melanoma : a population-based cohort study

Background The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer cohort study. Objectives To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life, and CM risk, overall and by histological subtypes and anatomical site. Methods We followed 165 712 women aged 30-75 years at inclusion from 1991-2007 to the end of 2015. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results The mean age at cohort enrolment was 49 years. During a median follow-up of 18 years, 1347 cases of CM were identified. No reproductive factors were clearly associated with CM risk. When stratifying by histological subtype we observed significant heterogeneity (P = 0 center dot 01) in the effect of length of ovulatory life on the risk of superficial spreading melanoma (HR 1 center dot 02, 95% CI 1 center dot 01-1 center dot 04 per year increase) and nodular melanoma (HR 0 center dot 97, 95% CI 0 center dot 94-1 center dot 01 per year increase). When stratifying by anatomical site, menopausal status (HR 0 center dot 54, 95% CI 0 center dot 31-0 center dot 92, postmenopausal vs. premenopausal) and menstrual cycle length (HR 1 center dot 07, 95% CI 1 center dot 01-1 center dot 13, per day increase) were associated with CM of the trunk, and significant heterogeneity between anatomical sites was observed for menopausal status (P = 0 center dot 04). Conclusions In this large population-based Norwegian cohort study, we did not find convincing evidence of an association between reproductive factors and risk of CM.Peer reviewe

Activity of Xenoestrogens at Nanomolar Concentrations in the E-Screen Assay

Our studies illustrate the difficulties that may be encountered during the estimation of low doses in vivo. High statistical power is required when the underlying dose-response curves are shallow. Through the use of large sample sizes and numerous repeats, the experimental power of the E-Screen assay was sufficiently high to measure effect magnitudes of around 1-2% with reliability. However, such resources are usually not available for in vivo testing, with the consequence that the statistical detection limits are considerably higher. If this coincides with shallow dose-response curves in the low-effect range (which is normally not measurable in vivo), the limited resolving power of in vivo assays may seriously constrain low-dose testing

Cervical cancer screening programmes and policies in 18 European countries

A questionnaire survey was conducted by the Epidemiology Working Group of the European Cervical Cancer Screening Network, and the International Agency for Research on Cancer, IARC, between August and December 2003 in 35 centres in 20 European countries with reliable cervical cancer incidence and/or mortality data in databanks held at IARC and WHO. The questionnaire was completed by 28 centres from 20 countries. The final tables included information on 25 centres from 18 countries. Six countries had started screening in the 1960s, whereas 10 countries or regions had started at least a pilot programme by 2003. There were six invitational and nine partially invitational programmes, the rest employing opportunistic screening only. Recommended lifetime number of smears varied from seven to more than 50. Coverage of smear test within the recommended screening interval (usually 3 or 5 years) was above 80% in three countries. Screening registration took place in 13 programmes. Eight programmes reported the rates of screen-detected cervical cancers and precursor lesions. There was wide variation in the CIN3 detection rates. International guidelines and quality assurance protocols are useful for monitoring and evaluating screening programmes systematically. Our survey indicated that the recommendations as currently given are met in only few European countries. Health authorities need to consider stronger measures and incentives than those laid out in the current set of recommendations

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Several dietary factors have been extensively investigated for associations with risk of breast cancer, but to date unequivocal evidence only exists for alcohol consumption. We sought to systematically evaluate the association between 92 dietary factors and breast cancer risk using a nutrient-wide association study approach. Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression with age as the time scale and adjustment for potential confounders, was used to quantify the association between each food or nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to evaluate in the independent replication cohort, the Netherlands Cohort Study (NLCS). During a median follow-up time of 15 years, 10,979 incident invasive breast cancers were identified in the women from the EPIC study. Six foods and nutrients were associated with risk of breast cancer when controlling the FDR at 0.05. Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% confidence interval (CI) 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 invasive breast cancer cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk of breast cancer in the NLCS. Our findings confirm the well-established increased risk of breast cancer associated with alcohol consumption, and suggest that higher intake of dietary fibre, and possibly fruit and carbohydrates, might be associated with reduced breast cancer risk

Alcohol and breast cancer risk: the alcoholism paradox

A population-based cohort study of 36 856 women diagnosed with alcoholism in Sweden between 1965 and 1995 found that alcoholic women had only a small 15% increase in breast-cancer incidence compared to the general female population. It is therefore apparent, contrary to expectation, that alcoholism does not increase breast-cancer risk in proportion to presumed ethanol intake. © 2000 Cancer Research Campaig

Agreement between diagnoses of childhood lymphoma assigned in Uganda and by an international reference laboratory

BACKGROUND: Correct diagnosis is key to appropriate treatment of cancer in children. However, diagnostic challenges are common in low-income and middle-income countries. The objective of the present study was to assess the agreement between a clinical diagnosis of childhood non- Hodgkin lymphoma (NHL) assigned in Uganda, a pathological diagnosis assigned in Uganda, and a pathological diagnosis assigned in The Netherlands. METHODS: The study included children with suspected NHL referred to the Mulago National Referral Hospital, Kampala, Uganda, between 2004 and 2008. A clinical diagnosis was assigned at the Mulago National Referral Hospital, where tissue samples were also obtained. Hematoxylin and eosin-stained slides were used for histological diagnosis in Uganda, and were re-examined in a pathology laboratory in The Netherlands, where additional pathological, virological and serological testing was also carried out. Agreement between diagnostic sites was compared using kappa statistics. RESULTS: Clinical and pathological diagnoses from Uganda and pathological diagnosis from The Netherlands was available for 118 children. The agreement between clinical and pathological diagnoses of NHL assigned in Uganda was 91% (95% confidence interval [CI] 84–95; kappa 0.84; P < 0.001) and in The Netherlands was 49% (95% CI 40–59; kappa 0.04; P = 0.612). When Burkitt’s lymphoma was considered separately from other NHL, the agreement between clinical diagnoses in Uganda and pathological diagnoses in Uganda was 69% (95% CI 59–77; kappa 0.56; P < 0.0001), and the corresponding agreement between pathological diagnoses assigned in The Netherlands was 32% (95% CI 24–41; kappa 0.05; P = 0.326). The agreement between all pathological diagnoses assigned in Uganda and The Netherlands was 36% (95% CI 28–46; kappa 0.11; P = 0.046). CONCLUSION: Clinical diagnosis of NHL in Uganda has a high probability of error compared with pathological diagnosis in Uganda and in The Netherlands. In addition, agreement on the pathological diagnosis of NHL between Uganda and The Netherlands is very low

Prevalence and risk factors associated with sexually transmitted infections (STIs) among women of reproductive age in Swaziland.

BACKGROUND: Sexually transmitted infections (STIs) remain an important public health problem with approximately half a billion new cases annually among persons aged 15-49 years. Epidemiological data on STIs among women of reproductive age in Swaziland are limited. The availability of epidemiological data on STIs and associated risk factors in this population is essential for the development of successful prevention, diagnosis and management strategies in the country. The study aimed to determine the prevalence and risk factors associated with STIs. METHODS: A total of 655 women aged 15-49 years were systematically enrolled from five health facilities using a cross-sectional study design. Cervical specimen were tested using GeneXpert CT/NG Assays for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), GeneXpertTV Assay for Trichomonas vaginalis (TV), and GeneXpert HPV Assays for hr-HPV. Blood samples were tested using Alere Determine HIV-1/2Ag/Ab Combo and Trinity Biotech Uni-Gold Recombigen HIV test for confirmation for HIV, and Rapid Plasma Reagin and TPHA test for confirmation for Treponema pallidum (syphilis). Genital warts were assessed prior to specimen collection. Survey weighted analyses were done to estimate the population burden of STIs. RESULTS: The four most common curable STIs: CT, NG, TV, Treponema pallidum (syphilis), as well as genital warts were considered in this study. The overall weighted prevalence of any of these five STIs was 19.4% (95% CI: 14.9-24.8), corresponding to 72 990 women with STIs in Swaziland. The estimated prevalences were 7.0% (95% CI: 4.1-11.2) for CT, 6.0% (95% CI: 3.8-8.8) for NG, 8.4% (95% CI: 5.4-12.8) for TV, 1.4% (95% CI: 1.1-10.2) for syphilis and 2.0% (95% CI: 1.0-11.4) for genital warts. The overall weighted HIV prevalence was 42.7% (95%CI: 35.7-46.2). Among hr-HPV positive women, 18.8% (95% CI: 13.1-26.3) had one STI, while 6.3% (95% CI: 3.3-11.7) had multiple STIs. Risk factors associated with STIs were being employed (OR = 2.2, 95% CI: 1.0-4.7), self-employed (OR = 2.8, 95% CI: 1.5-5.5) and being hr-HPV positive (OR = 2.0, 95% CI: 1.3-3.1). Age (0.9, 95% CI: 0.8-0.9), being married (OR = 0.4, 95% CI: 0.3-0.7) and not using condoms with regular partners (OR = 0.5, 95% CI: 0.3-0.9) were inversely associated with STIs. CONCLUSION: STIs are highly prevalent among women of reproductive age in Swaziland. Thus, a comprehensive STIs screening, surveillance and treatment programme would be justified and could potentially lower the burden of STIs in the country