Anthropometric features and cutaneous melanoma risk: A prospective cohort study in French women

BackgroundEpidemiological studies on anthropometric features and cutaneous melanoma risk in women yielded inconsistent results, with few analyses involving prospective cohort data. Our objective was to explore several anthropometric characteristics in relation to the risk of melanoma in women.MethodsWe prospectively analysed data from E3N, a French cohort involving 98,995 women born in 1925–1950. Participants completed self-administered questionnaires sent biennially over 1990–2008. Relative risks (RRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards regression models, adjusted for age, number of naevi, freckling, skin and hair colour, skin sensitivity to sun exposure, residential sun exposure, and physical activity.ResultsHeight was positively associated with melanoma in age-adjusted models only (RR = 1.27, 95% CI = 1.05–1.55 for ≥164 cm vs. <160 cm; P for trend = 0.02). After full adjustment, there was a significantly positive relationship between sitting-to-standing height ratio and melanoma risk (RR = 1.40, 95% CI = 1.06–1.86 for ≥0.533 vs. <0.518; P for trend = 0.02). A large body shape at menarche was inversely associated with the risk of melanoma (RR = 0.78, 95% CI = 0.62–0.98; compared with lean). However, weight, body mass index, body surface area, waist or hip circumference, sitting height or leg length were not significantly associated with risk.ConclusionThese results suggest that height, sitting-to-standing height ratio and body shape at menarche may be associated with melanoma risk. Further research is required to confirm these relationships and better understand the underlying mechanisms.     

生物样本库是生物医学研究的重要基础

在生物医学研究飞速发展的今天,随着对健康和疾病认识的不断深入,传统的单病因、单基因研究模式已难以胜任复杂疾病的研究.医学科学的发展需要一种能提供疾病相关的、具有普遍意义的、全局式的分子信息数据库.生物样本库在其中所能发挥的关键作用得到了越来越多的重视.它从最初的小作坊模式经过100多年,尤其是近30年的快速发展已经演化成为科研院所和政府支持的生物样本库、商业化生物样本库及以人口为基础的生物银行等多种模式.伴随存储样本数据信息的复杂度不断快速增加,生物样本库除了收集样本相关的基本数据和诊断信息外,还延伸到配套信息,包括参加人和病人的多种表型,到目前已经迅速扩展到基因组学、蛋白质组学及其他的组学信息.如何科学地建设和管理这种大型复杂模式的生物样本库成为医学科学领域亟待规范、解决的问题.本文将从生物样本库的发展入手重点讨论其建设、管理和应用.     

Telomere length and risk of glioma

BackgroundTelomere length in blood or buccal cell DNA has been associated with risk of various cancers. Glioma can be a highly malignant brain tumor and has few known risk factors. Genetic variants in or near RTEL1 and TERT, key components of telomere biology, are associated with glioma risk. Therefore, we evaluated the association between relative telomere length (RTL) and glioma in a prospective study.Materials and methodsWe performed a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. RTL was determined by quantitative PCR on blood or buccal cell DNA obtained at least 2 years prior to diagnosis from 101 individuals with glioma cases. Healthy controls (n = 198) were matched to cases (2:1) on age, gender, smoking status, calendar year, and DNA source. Conditional logistic regression was used to investigate the association between RTL and glioma.ResultsAs expected, RTL declined with increasing age in both cases and controls. There was no statistically significant association between RTL and glioma overall. An analysis stratified by gender suggested that short RTL (1st tertile) in males was associated with glioma (odds ratio, [OR] = 2.29, 95% confidence interval [CI] 1.02–5.11); this association was not observed for females (OR = 0.41, 95% CI 0.14–1.17).ConclusionsThis prospective study did not identify significant associations between RTL and glioma risk, but there may be gender-specific differences. Larger, prospective studies are needed to evaluate these findings.     

Chronotype,depression and hippocampal volume: cross-sectional associations from the UK Biobank

Diurnal preference for evening time has been associated with increased odds for current depression and a number of indices of the disorder. In the current study, the association between chronotype and depression was explored in a population-based sample of 5360 adults aged between 40 and 70 years. Previous work has also suggested that larger hippocampal volume may be protective against depression. In an additional, exploratory analysis, hippocampal volume was compared in never-depressed early and late chronotypes (N= 3004). Definite eveningness was significantly associated with increased odds for probable lifetime depression after controlling for a number of confounding factors including neuroticism. Hippocampal volume did not differ between never-depressed early and late chronotypes. The current results extend previous work and add further weight to the argument that late chronotype represents a risk factor for depression.     

Reproductive factors and the risk of incident dementia: A cohort study of UK Biobank participants

BackgroundWomen’s reproductive factors have been associated with the risk of dementia; however, these findings remain uncertain. This study aimed to examine the risk of incident all-cause dementia associated with reproductive factors in women and the number of children in both sexes and whether the associations vary by age, socioeconomic status (SES), smoking status, and body mass index (BMI) in the UK Biobank.Methods and findingsA total of 273,240 women and 228,957 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia. Multiple adjusted models included age at study entry, SES, ethnicity, smoking status, systolic blood pressure, BMI, history of diabetes mellitus, total cholesterol, antihypertensive drugs, and lipid-lowering drugs. Over a median of 11.8 years follow-up, 1,866 dementia cases were recorded in women and 2,202 in men. Multiple adjusted HRs ((95% confidence intervals (CIs)), p-value) for dementia were 1.20 (1.08, 1.34) (p = 0.016) for menarche <12 years and 1.19 (1.07, 1.34) (p = 0.024) for menarche >14 years compared to 13 years; 0.85 (0.74, 0.98) (p = 0.026) for ever been pregnant; 1.43 (1.26, 1.62) (p < 0.001) for age at first live birth <21 compared to 25 to 26 years; 0.82 (0.71, 0.94) (p = 0.006) for each abortion; 1.32 (1.15, 1.51) (p = 0.008) for natural menopause at <47 compared to 50 years; 1.12 (1.01, 1.25) (p = 0.039) for hysterectomy; 2.35 (1.06, 5.23) (p = 0.037) for hysterectomy with previous oophorectomy; and 0.80 (0.72, 0.88) (p < 0.001) for oral contraceptive pills use. The U-shaped associations between the number of children and the risk of dementia were similar for both sexes: Compared with those with 2 children, for those without children, the multiple adjusted HR ((95% CIs), p-value) was 1.18 (1.04, 1.33) (p = 0.027) for women and 1.10 (0.98, 1.23) (p = 0.164) for men, and the women-to-men ratio of HRs was 1.09 (0.92, 1.28) (p = 0.403); for those with 4 or more children, the HR was 1.14 (0.98, 1.33) (p = 0.132) for women and 1.26 (1.10, 1.45) (p = 0.003) for men, and the women-to-men ratio of HRs was 0.93 (0.76, 1.14) (p = 0.530). There was evidence that hysterectomy (HR, 1.31 (1.09, 1.59), p = 0.013) and oophorectomy (HR, 1.39 (1.08, 1.78), p = 0.002) were associated with a higher risk of dementia among women of relatively lower SES only. Limitations of the study include potential residual confounding and self-reported measures of reproductive factors, as well as the limited representativeness of the UK Biobank population.ConclusionsIn this study, we observed that some reproductive events related to shorter cumulative endogenous estrogen exposure in women were associated with higher dementia risk, and there was a similar association between the number of children and dementia risk between women and men.

In a cohort study, Jessica Gong and colleagues investigate associations between reproductive factors, number of children, and dementia among individuals in the UK Biobank.     

Democratic governance of genomics: the case of UK Biobank

Biobanks are collections of human biological tissue used for genomics research. This promises a better understanding of the gene-based contribution to common disease and development of a more personalized approach to healthcare with safer drugs and more effective treatment. However, biobanks are also controversial owing to the ethical, legal, social and political issues raised about their collection and use of biological samples. Therefore, their democratic governance is not only a normative challenge but also an empirical one. This paper is concerned with both challenges: it attempts to “evaluate” processes of democratic governance of genomics by focusing on the case of UK Biobank. The overall argument is that although the UK Biobank performs well in terms of general democratic governance structures, there are epistemological and practical limits to specific democratic governance processes.     

Associations between chronotype,morbidity and mortality in the UK Biobank cohort

Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38–73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24–1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20–1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19–1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18–1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004–1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00–1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.     

Incidence of and risk factors for Motor Neurone Disease in UK women: a prospective study

ABSTRACT: BACKGROUND: Motor neuron disease (MND) is a severe neurodegenerative disease with largely unknown etiology. Most epidemiological studies are hampered by small sample sizes and/or the retrospective collection of information on behavioural and lifestyle factors. METHODS: 1.3 million women from the UK Million Women Study, aged 56 years on average at recruitment, were followed up for incident and/or fatal MND using NHS hospital admission and mortality data. Adjusted relative risks were calculated using Cox regression models. FINDINGS: During follow-up for an average of 9.2 years, 752 women had a new diagnosis of MND. Age-specific rates increased with age, from 1.9 (95% CI 1.3 - 2.7) to 12.5 (95% CI 10.2 - 15.3) per 100,000 women aged 50-54 to 70-74, respectively, giving a cumulative risk of diagnosis with the disease of 1. 74 per 1000 women between the ages of 50 and 75 years. There was no significant variation in risk of MND with region of residence, socio-economic status, education, height, alcohol use, parity, use of oral contraceptives or hormone replacement therapy. Ever-smokers had about a 20% greater risk than never smokers (RR 1.19 95% CI 1.02 to 1.38, p=0.03). There was a statistically significant reduction in risk of MND with increasing body mass index (pfor trend=0.009): obese women (body mass index, 30 kg/m2 or more) had a 20% lower risk than women of normal body mass index (20 to <25 Kg/m2)(RR 0.78 95% CI 0.65-0.94; p=0.03). This effect persisted after exclusion of the first three years of follow-up. Interpretation. MND incidence in UK women rises rapidly with age, and an estimated 1 in 575 women are likely to be affected between the ages of 50 and 75 years. Smoking slightly increases the risk of MND, and adiposity in middle age is associated with a lower risk of the disease.     

Getting a Fair Share: Attitudes and Perceptions of Biobank Stakeholders Concerning the Fairness of Sample Sharing

Biobanks are essential tools for furthering a broad range of medical research areas. However, despite the plethora of national and international laws and guidelines which apply to them, the access and sharing policies of biobanks are only sparsely addressed by regulatory bodies. The ‘give and take’ process of biosample sharing is largely left up to biobank stakeholders themselves to oversee; it is therefore both in stakeholders' power, and in their interest, to ensure that sample accessibility is fair. This is an important step in motivating researchers to collaborate and pool samples, and is crucial to fostering trust in the absence of universally accepted standard practices. To date, little attention has been paid to how fairness considerations affect scientific material sharing, and no empirical research has been carried out to determine the role that fairness plays in collaborative studies. In order to begin to gain understanding in this area, we interviewed 36 biobank stakeholders currently working in Switzerland, focusing on their perceptions of current and optimal fair sharing practices. Our findings reveal that fairness is an important feature of exchange situations for these stakeholders, and that they have well‐formed notions about the practical elements of fair sample access, although ideas about the concept of fairness itself are vague. In order to support efforts to network biobanks, attention should be paid to this issue to reassure all involved that they are getting a fair share in their cooperative efforts.     

Genetic polymorphisms involved in the inflammatory response and lung cancer risk: A case-control study in Japan

Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1β (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR = 1.64, 95% CI = 1.19–2.26) and IL6 rs1800796 (OR = 1.41, 95% CI = 1.02–1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (P_interaction = 0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer.     

Body size and composition and risk of site-specific cancers in the UK Biobank and large international consortia: A mendelian randomisation study

BackgroundEvidence for the impact of body size and composition on cancer risk is limited. This mendelian randomisation (MR) study investigates evidence supporting causal relationships of body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), and height with cancer risk.Methods and findingsSingle nucleotide polymorphisms (SNPs) were used as instrumental variables for BMI (312 SNPs), FMI (577 SNPs), FFMI (577 SNPs), and height (293 SNPs). Associations of the genetic variants with 22 site-specific cancers and overall cancer were estimated in 367,561 individuals from the UK Biobank (UKBB) and with lung, breast, ovarian, uterine, and prostate cancer in large international consortia. In the UKBB, genetically predicted BMI was positively associated with overall cancer (odds ratio [OR] per 1 kg/m² increase 1.01, 95% confidence interval [CI] 1.00–1.02; p = 0.043); several digestive system cancers: stomach (OR 1.13, 95% CI 1.06–1.21; p < 0.001), esophagus (OR 1.10, 95% CI 1.03, 1.17; p = 0.003), liver (OR 1.13, 95% CI 1.03–1.25; p = 0.012), and pancreas (OR 1.06, 95% CI 1.01–1.12; p = 0.016); and lung cancer (OR 1.08, 95% CI 1.04–1.12; p < 0.001). For sex-specific cancers, genetically predicted elevated BMI was associated with an increased risk of uterine cancer (OR 1.10, 95% CI 1.05–1.15; p < 0.001) and with a lower risk of prostate cancer (OR 0.97, 95% CI 0.94–0.99; p = 0.009). When dividing cancers into digestive system versus non-digestive system, genetically predicted BMI was positively associated with digestive system cancers (OR 1.04, 95% CI 1.02–1.06; p < 0.001) but not with non-digestive system cancers (OR 1.01, 95% CI 0.99–1.02; p = 0.369). Genetically predicted FMI was positively associated with liver, pancreatic, and lung cancer and inversely associated with melanoma and prostate cancer. Genetically predicted FFMI was positively associated with non-Hodgkin lymphoma and melanoma. Genetically predicted height was associated with increased risk of overall cancer (OR per 1 standard deviation increase 1.09; 95% CI 1.05–1.12; p < 0.001) and multiple site-specific cancers. Similar results were observed in analyses using the weighted median and MR–Egger methods. Results based on consortium data confirmed the positive associations between BMI and lung and uterine cancer risk as well as the inverse association between BMI and prostate cancer, and, additionally, showed an inverse association between genetically predicted BMI and breast cancer. The main limitations are the assumption that genetic associations with cancer outcomes are mediated via the proposed risk factors and that estimates for some lower frequency cancer types are subject to low precision.ConclusionsOur results show that the evidence for BMI as a causal risk factor for cancer is mixed. We find that BMI has a consistent causal role in increasing risk of digestive system cancers and a role for sex-specific cancers with inconsistent directions of effect. In contrast, increased height appears to have a consistent risk-increasing effect on overall and site-specific cancers.

Mathew Vithayathil and colleagues study associations of body mass index and other measures with incidence of specific cancers.     

Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.     

Consumption of coffee and tea and risk of developing stroke,dementia, and poststroke dementia: A cohort study in the UK Biobank

BackgroundPrevious studies have revealed the involvement of coffee and tea in the development of stroke and dementia. However, little is known about the association between the combination of coffee and tea and the risk of stroke, dementia, and poststroke dementia. Therefore, we aimed to investigate the associations of coffee and tea separately and in combination with the risk of developing stroke and dementia.Methods and findingsThis prospective cohort study included 365,682 participants (50 to 74 years old) from the UK Biobank. Participants joined the study from 2006 to 2010 and were followed up until 2020. We used Cox proportional hazards models to estimate the associations between coffee/tea consumption and incident stroke and dementia, adjusting for sex, age, ethnicity, qualification, income, body mass index (BMI), physical activity, alcohol status, smoking status, diet pattern, consumption of sugar-sweetened beverages, high-density lipoprotein (HDL), low-density lipoprotein (LDL), history of cancer, history of diabetes, history of cardiovascular arterial disease (CAD), and hypertension. Coffee and tea consumption was assessed at baseline. During a median follow-up of 11.4 years for new onset disease, 5,079 participants developed dementia, and 10,053 participants developed stroke. The associations of coffee and tea with stroke and dementia were nonlinear (P for nonlinear <0.01), and coffee intake of 2 to 3 cups/d or tea intake of 3 to 5 cups/d or their combination intake of 4 to 6 cups/d were linked with the lowest hazard ratio (HR) of incident stroke and dementia. Compared with those who did not drink tea and coffee, drinking 2 to 3 cups of coffee and 2 to 3 cups of tea per day was associated with a 32% (HR 0.68, 95% CI, 0.59 to 0.79; P < 0.001) lower risk of stroke and a 28% (HR, 0.72, 95% CI, 0.59 to 0.89; P = 0.002) lower risk of dementia. Moreover, the combination of coffee and tea consumption was associated with lower risk of ischemic stroke and vascular dementia. Additionally, the combination of tea and coffee was associated with a lower risk of poststroke dementia, with the lowest risk of incident poststroke dementia at a daily consumption level of 3 to 6 cups of coffee and tea (HR, 0.52, 95% CI, 0.32 to 0.83; P = 0.007). The main limitations were that coffee and tea intake was self-reported at baseline and may not reflect long-term consumption patterns, unmeasured confounders in observational studies may result in biased effect estimates, and UK Biobank participants are not representative of the whole United Kingdom population.ConclusionsWe found that drinking coffee and tea separately or in combination were associated with lower risk of stroke and dementia. Intake of coffee alone or in combination with tea was associated with lower risk of poststroke dementia.

In a cohort study, Yuan Zhang and colleagues investigate the associations between coffee and tea consumption and risk of stroke and dementia among participants older than 50 years of age in the UK Biobank.     

A prospective cohort study of pregnancy risk factors and birth outcomes in Aboriginal women

Background

Aboriginal women have been identified as having poorer pregnancy outcomes than other Canadian women, but information on risk factors and outcomes has been acquired mostly from retrospective databases. We compared prenatal risk factors and birth outcomes of First Nations and Métis women with those of other participants in a prospective study.

Methods

During the 12-month period from July 1994 to June 1995, we invited expectant mothers in all obstetric practices affiliated with a single teaching hospital in Edmonton to participate. Women were recruited at their first prenatal visit and followed through delivery. Sociodemographic and clinical data were obtained by means of a patient questionnaire, and microbiological data were collected at 3 points during gestation: in the first and second trimesters and during labour. Our primary outcomes of interest were low birth weight (birth weight less than 2500 g), prematurity (birth at less than 37 weeks'' gestation) and macrosomia (birth weight greater than 4000 g).

Results

Of the 2047 women consecutively enrolled, 1811 completed the study through delivery. Aboriginal women accounted for 70 (3.9%) of the subjects who completed the study (45 First Nations women and 25 Métis women). Known risk factors for adverse pregnancy outcome were more common among Aboriginal than among non-Aboriginal women, including previous premature infant (21% v. 11%), smoking during the current pregnancy (41% v. 13%), presence of bacterial vaginosis in midgestation (33% v. 13%) and poor nutrition as measured by meal consumption. Although Aboriginal women were less likely than non-Aboriginal women to have babies of low birth weight (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.52–4.15) or who were born prematurely (OR 1.45, 95% CI 0.57–3.72) and more likely to have babies with macrosomia (OR 2.04, 95% CI 1.03–4.03), these differences were lower and statistically nonsignificant after adjustment for smoking, cervicovaginal infection and income (adjusted OR for low birth weight 0.85, 95% CI 0.19–3.78; for prematurity 0.90, 95% CI 0.21–3.89; and for macrosomia 2.12, 95% CI 0.84-5.36).

Interpretation

After adjustment for potential confounding factors, we found no statistically significant relation between Aboriginal status and birth outcome.It is generally recognized that Aboriginal women experience poorer birth outcomes than other North American women, including higher rates of stillbirth,¹ low-birth-weight infants^1,2,3 and prematurity.^2,3 Although significant efforts have been made to reduce Aboriginal infant mortality rates, these rates remain higher than for other infants in both Canada⁴ and the United States.⁵ Little is known about the reasons for differences in birth outcomes, although social, economic, medical and prenatal care factors have been suggested. Recent publications, based on retrospective analyses of large databases, have confirmed disparities in birth outcomes between Aboriginal and all other groups,^3,6,7 but there is a paucity of prospective data. In addition, although the term “Aboriginal” refers to a heterogeneous population comprising First Nations people, Métis and Inuit, there are few comparisons between specific Aboriginal groups or of Aboriginal groups with the general population.We report here the results of a prospective study in a general obstetric population, comparing birth outcomes and known pregnancy risk factors of Aboriginal women with those of non-Aboriginal Canadian women. In addition to well-recognized socioeconomic and reproductive risk factors, we investigated the prevalence of maternal cervicovaginal infections, which have been increasingly linked to prematurity.^8,9     

Demographic,social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP)

BackgroundLittle is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia.MethodsBaseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsIn a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04–1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24–2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08–1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08–2.64), and current (OR 3.42, 95% CI 1.81–6.47) or former (OR 1.95, 95% CI 1.33–2.86) smokers.ConclusionThe consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.