The combined influence of parental education and preterm birth on school performance.

BACKGROUND: Social background and birth characteristics are generally found to be independently associated with school achievements but the underlying mechanisms are not fully understood. This study aimed to explore how parental education and shorter gestational age jointly influence school performance in a cohort of Swedish children. METHODS: 10,835 children born between 1973 and 1981 were studied, the third generation of the register-based Uppsala Multigenerational Birth Cohort. Ordinal logistic regression models were fitted to estimate OR of achieving middle and high grades in Swedish language at age 16 years, relative to low grade, by parental education and own gestational age, adjusting for potential confounders. RESULTS: In children from families with lower parental education, the adjusted OR of receiving a higher grade was 0.54 (95% CI 0.41 to 0.71) for preterm (<37 completed weeks) compared with full-term births. This estimate did not change when adjusted for several potential confounders (0.59; CI 0.44 to 0.79). When different cut-points were selected to define preterm birth, the estimated OR for those with low parental education decreased linearly from 0.83 (CI 0.72 to 0.96) using less than 39 weeks as the cut-point, to 0.52 (CI 0.30 to 0.90) using less than 35 weeks. There was no evidence of significant effects of shorter gestational age for children with parents from other educational groups. CONCLUSIONS: The disadvantage of shorter gestational age on the chance of achieving higher grades in Swedish language was confined to children from families in which none of the parents had higher education. This suggests that the detrimental influence of shorter gestational age on school performance in language may be avoidable

Health needs of the Roma population in the Czech and Slovak Republics.

In the growing literature on the human rights of Roma people in Central Europe, their relatively poor health status is often mentioned. However, little concrete information exists about the contemporary health status of the Roma in this region. We sought information on the health of the Roma in two of countries with significant Roma minorities, the Czech and Slovak Republics, by means of systematic searches for literature on the health of Roma people published in Czech or Slovak or by authors from the two countries. Published research on health of the Roma population is sparse. The topics that have received attention suggest a focus on concepts of contagion or social Darwinism, indicating a greater concern with the health needs of the majority populations with which they live. What limited evidence exists indicates that the health needs of the Roma population are considerable. With very few exceptions, the health status of Roma is worse than that of non-Roma population in both countries. The burden of communicable disease among Roma is high and diseases associated with poor hygiene seem to be particularly important. Evidence on health care suggests poor communication between Roma and health workers and low uptake of preventative care. The health needs of Roma lack visibility, not only because of the absence of research but also the absence of advocacy on their behalf. Since 1989, Czech and Slovak researchers have largely turned away from health research on particular ethnic groups. This probably reflects a growing sensitivity about stigmatising Roma, but it also makes it difficult to know how their circumstances might be improved. There is a need for further research into the health of Roma people with particular emphasis on non-communicable disease and for interventions that would improve their health

Intergenerational correlations in size at birth and the contribution of environmental factors: The Uppsala Birth Cohort Multigenerational Study, Sweden, 1915-2002.

Sizes at birth of parents and their children are known to be correlated, reflecting in part the influence of fetal and maternal genes. Sociodemographic factors, regarded as aspects of the shared environment across generations, would also be expected to contribute, but evidence is limited. In the present study, the authors aimed to quantify the role of the shared environment in explaining intergenerational correlations in birth weight and length by using data across 3 consecutive generations from the Uppsala Birth Cohort Multigenerational Study in Uppsala, Sweden. That study included birth and sociodemographic data on 7,657 singletons born in Uppsala in 1915-1929 (generation 1) and their grandchildren (generation 3). Standard regression and biometric models were used to study the correlations in size at birth of generation 1-generation 3 pairs. The data showed stronger correlations in maternal pairs than in paternal pairs for birth weight (0.125 vs. 0.096, P = 0.02) but not for birth length (0.097 vs. 0.093, P = 0.77). These correlations were not reduced by adjustment for sociodemographic factors in regression models. In contrast, significant shared-environment contributions to the intergenerational correlations were identified in biometric models, averaging 14% for both birth measures. These models assumed a common latent factor for the sociodemographic variables. The present results show that the shared environment moderately but significantly contributes to intergenerational correlations

Women's perception, attitudes, and intended behavior towards predictive epigenetic risk testing for female cancers in 5 European countries: A cross-sectional online survey

BACKGROUND: Epigenetic markers might be used for risk-stratifying cancer screening and prevention programs in the future. Although the clinical utility of consequent epigenetic tests for risk stratification is yet to be proven, successful adoption into clinical practice also requires the public's acceptance of such tests. This cross-sectional online survey study sought to learn for the first time about European women's perceptions, attitudes, and intended behavior regarding a predictive epigenetic test for female cancer (breast, ovarian, cervical, and endometrial) risks. METHODS: 1675 women (40-75 years) from five European countries (Czech Republic, Germany, United Kingdom, Italy, Sweden), drawn from online panels by the survey sampling company Harris Interactive (Germany), participated in an online survey where they first received online leaflet information on a predictive epigenetic test for female cancer risks and were subsequently queried by an online questionnaire on their desire to know their female cancer risks, their perception of the benefit-to-harm ratio of an epigenetic test predicting female cancer risks, reasons in favor and disfavor of taking such a test, and their intention to take a predictive epigenetic test for female cancer risks. RESULTS: Most women desired information on each of their female cancer risks, 56.6% (95% CI: 54.2-59.0) thought the potential benefits outweighed potential harms, and 75% (72.0-77.8) intended to take a predictive epigenetic test for female cancer risks if freely available. Results varied considerably by country with women from Germany and the Czech Republic being more reserved about this new form of testing than women from the other three European countries. The main reason cited in favor of a predictive epigenetic test for female cancer risks was its potential to guide healthcare strategies and lifestyle changes in the future, and in its disfavor was that it may increase cancer worry and coerce unintended lifestyle changes and healthcare interventions. CONCLUSIONS: A successful introduction of predictive epigenetic tests for cancer risks will require a balanced and transparent communication of the benefit-to-harm ratio of healthcare pathways resulting from such tests in order to curb unjustified expectations and at the same time to prevent unjustified concerns

Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies.

BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p&lt;0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p&lt;0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p&lt;0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p&lt;0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p&lt;0·01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Risk Factors for Double Primary Breast and Ovarian Cancer in Women Across the Risk Spectrum

Advancements in medicine and technology have led to an increasing number of cancer survivors. The development of a second primary cancer is one of the most severe sequelae of a cancer diagnosis, particularly for cancers that lack an effective screening tool as with ovarian cancer. Breast and ovarian cancer are major causes of morbidity and mortality in women; in the U.S., breast cancer has the highest incidence in women and ovarian cancer is the most fatal of gynecological cancers. Further, these two cancers have been found to co-occur. Along with possible treatment effects of the first cancer, shared risk factors, shared genetics, and interactions between these two have been hypothesized to contribute to their co-occurrence. Research on shared risk factors for second cancers is lacking and being able to identify potentially modifiable factors associated with second primary cancer could improve clinical recommendations for cancer survivors. Therefore, this dissertation examined risk factors for the development of double primary breast and ovarian cancer (DPBOC) in three parts 1) a comprehensive review of the literature to identify studies assessing risk factors for DPBOC, 2) a case-control study assessing the association between three potentially-modifiable risk factors (oral contraceptive (OC) use, parity, and breastfeeding), and risk of second primary ovarian cancer following breast cancer (BR-OV), second primary breast cancer following ovarian cancer (OV-BR), single primary ovarian cancer (OV), and single primary breast cancer (BR), and 3) a cohort study assessing OC use, parity, and breastfeeding and risk of BR-OV, OV, and BR. The comprehensive review identified few studies assessing epidemiologic risk factors for the development of DPBOC and most of the findings were not statistically significant. The majority of studies focused on treatment of breast cancer and risk of second primary ovarian cancer. While most of the findings on chemotherapy, radiotherapy, and Tamoxifen were heterogeneous and lacked statistical significance, hormone therapy for breast cancer may be associated with an increased risk of second primary ovarian cancer. The majority of studies on genetic risk factors for DPBOC looked at BRCA1/2 mutations or a crude measure of family history. Both BRCA1/2 and family history were consistently associated with risk of DPBOC, but studies varied on the extent of this risk due to differences in study design, exposure and outcome definition, and statistical power. No studies were identified examining DNA methylation and risk of DPBOC. The case-control study used data from the three clinic-based sites of the Breast Cancer Family Registry (BCFR) which consisted of women from breast and ovarian cancer families. We observed an inverse association with both OC use (OR=0.38, 95% CI: 0.22, 0.60) and breastfeeding (OR=0.52, 95% CI: 0.31, 0.87) and risk of DPBOC, but a positive association with parity (≥2 full-term pregnancies: OR=5.78, 95% CI: 2.82, 14.58), regardless of diagnosis order (BR-OV or OV-BR). We found similar associations for our OV and BR outcomes as well. When we examined differences between high and average risk women (using BRCA1/2 mutation status and predicted lifetime risk of breast or ovarian cancer), the inverse association with OC use only remained in women at average risk while the inverse association with breastfeeding only remained in women at high risk. As the positive association with parity and all of our outcomes disagreed with our hypothesis we conducted several sensitivity analyses to explore this finding. Survivor bias may have influenced our results as we observed differences in our findings between cases diagnosed ≤2 or ≤5 years before the baseline interview (pseudo-incident) and cases diagnosed >2 or >5 years before the baseline interview (prevalent). Specifically, the inverse association with OC use and all of our outcomes, and the positive association with parity and all of our outcomes were attenuated in the pseudo-incident group. To address concerns of selection and information bias in our case-control study, we conducted a cohort study using data from The Breast Cancer Prospective Family Study Cohort (ProF-SC). In contrast to our case-control findings, we observed a suggestive positive association between OC use and risk of BR-OV (HR=1.62, 95% CI: 0.91, 2.90) which became stronger in women at high risk, and an inverse association between having two or more full-term pregnancies compared to nulliparous and risk of BR-OV (HR=0.47, 95% CI: 0.22, 0.97) which did not vary by underlying risk of breast and ovarian cancer. However, our BR-OV results may have similarly been influenced by survivor bias as we observed differences in our results between our pseudo-incident and prevalent BR-OV cases; the association between OC use and BR-OV only remained in the prevalent cases. In summary, the results of this dissertation highlight the methodological challenges in the study of second primary cancers and the importance of considering survivor bias in a cohort of cancer survivors being followed for second cancers. Further, our results are suggestive of a discordant effect of OC use on first primary versus second primary ovarian cancer which should be explored in future studies