Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent.
We used serial questionnaire information from the Generations ...Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake.
Among 102,927 women recruited 2003-2013, with an average of 7.7 years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never smokers) was 1.14 (95% CI 1.03-1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08-1.43; P = 0.002) for starting smoking at ages < 17 years, and 1.23 (1.07-1.41; P = 0.004) for starting smoking 1-4 years after menarche. Breast cancer risk was not statistically associated with interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12-1.62; P = 0.002) had a significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women without (ever smoker vs never smoker HR 1.07; 95% CI 0.96-1.20; P = 0.22). The interaction was prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at menarche (P = 0.0001).
Smoking was associated with a modest but significantly increased risk of breast cancer, particularly among women who started smoking at adolescent or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater for women with a family history of the disease.
Endophenotypes are quantitative, laboratory-based measures representing intermediate links in the pathways between genetic variation and the clinical expression of a disorder. Ideal endophenotypes ...exhibit deficits in patients, are stable over time and across shifts in psychopathology, and are suitable for repeat testing. Unfortunately, many leading candidate endophenotypes in schizophrenia have not been fully characterized simultaneously in large cohorts of patients and controls across these properties. The objectives of this study were to characterize the extent to which widely-used neurophysiological and neurocognitive endophenotypes are: 1) associated with schizophrenia, 2) stable over time, independent of state-related changes, and 3) free of potential practice/maturation or differential attrition effects in schizophrenia patients (SZ) and nonpsychiatric comparison subjects (NCS). Stability of clinical and functional measures was also assessed.
Participants (SZ n = 341; NCS n = 205) completed a battery of neurophysiological (MMN, P3a, P50 and N100 indices, PPI, startle habituation, antisaccade), neurocognitive (WRAT-3 Reading, LNS-forward, LNS-reorder, WCST-64, CVLT-II). In addition, patients were rated on clinical symptom severity as well as functional capacity and status measures (GAF, UPSA, SOF). 223 subjects (SZ n = 163; NCS n = 58) returned for retesting after 1 year.
Most neurophysiological and neurocognitive measures exhibited medium-to-large deficits in schizophrenia, moderate-to-substantial stability across the retest interval, and were independent of fluctuations in clinical status. Clinical symptoms and functional measures also exhibited substantial stability. A Longitudinal Endophenotype Ranking System (LERS) was created to rank neurophysiological and neurocognitive biomarkers according to their effect sizes across endophenotype criteria.
The majority of neurophysiological and neurocognitive measures exhibited deficits in patients, stability over a 1-year interval and did not demonstrate practice or time effects supporting their use as endophenotypes in neural substrate and genomic studies. These measures hold promise for informing the "gene-to-phene gap" in schizophrenia research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Family history is an important risk factor for breast cancer incidence, but the parameters conventionally used to categorize it are based solely on numbers and/or ages of breast cancer cases ...in the family and take no account of the size and age-structure of the woman’s family.
Methods
Using data from the Generations Study, a cohort of over 113,000 women from the general UK population, we analyzed breast cancer risk in relation to first-degree family history using a family history score (FHS) that takes account of the expected number of family cases based on the family’s age-structure and national cancer incidence rates.
Results
Breast cancer risk increased significantly (
P
trend
< 0.0001) with greater FHS. There was a 3.5-fold (95% CI 2.56–4.79) range of risk between the lowest and highest FHS groups, whereas women who had two or more relatives with breast cancer, the strongest conventional familial risk factor, had a 2.5-fold (95% CI 1.83–3.47) increase in risk. Using likelihood ratio tests, the best model for determining breast cancer risk due to family history was that combining FHS and age of relative at diagnosis.
Conclusions
A family history score based on expected as well as observed breast cancers in a family can give greater risk discrimination on breast cancer incidence than conventional parameters based solely on cases in affected relatives. Our modeling suggests that a yet stronger predictor of risk might be a combination of this score and age at diagnosis in relatives.
There has been a worldwide epidemic of obesity in recent decades. In animal studies, there is convincing evidence that light exposure causes weight gain, even when calorie intake and physical ...activity are held constant. Disruption of sleep and circadian rhythms by exposure to light at night (LAN) might be one mechanism contributing to the rise in obesity, but it has not been well-investigated in humans. Using multinomial logistic regression, we examined the association between exposure to LAN and obesity in questionnaire data from over 100,000 women in the Breakthrough Generations Study, a cohort study of women aged 16 years or older who were living in the United Kingdom and recruited during 2003-2012. The odds of obesity, measured using body mass index, waist:hip ratio, waist:height ratio, and waist circumference, increased with increasing levels of LAN exposure (P < 0.001), even after adjustment for potential confounders such as sleep duration, alcohol intake, physical activity, and current smoking. We found a significant association between LAN exposure and obesity which was not explained by potential confounders we could measure. While the possibility of residual confounding cannot be excluded, the pattern is intriguing, accords with the results of animal experiments, and warrants further investigation.
Background Schizophrenia patients have deficits across a broad range of important cognitive and clinical domains. Synchronization of oscillations in the gamma frequency range (∼40 Hz) is associated ...with many normal cognitive functions and underlies at least some of the deficits observed in schizophrenia patients. Recent studies have demonstrated that gamma oscillations are modulated by the phase of theta waves, and this cross-frequency coupling indicates that a complex and hierarchical organization governs neural oscillatory dynamics. The aims of the present study were to determine if schizophrenia patients have abnormalities in the amplitude, synchrony, and cross-frequency coupling of gamma and theta oscillations in response to gamma-frequency steady-state stimulation and if abnormal neural oscillatory dynamics are associated with cognitive deficits in schizophrenia. Methods Schizophrenia patients ( n = 234) and healthy control subjects ( n = 188) underwent electroencephalography testing in response to 40-Hz auditory steady-state stimulation. Cognitive functions were assessed with a battery of neuropsychological tests. Results Schizophrenia patients had significantly reduced gamma intertrial phase coherence, increased theta amplitude, and intact cross-frequency coupling relative to healthy control subjects. In schizophrenia patients, increased theta amplitude was associated with poor verbal memory performance. Conclusions Results suggest that schizophrenia patients have specific alterations in both gamma and theta oscillations, but these deficits occur in the context of an intact hierarchical organization of their cross-frequency modulation in response to 40-Hz steady-state stimulation. Cortical oscillatory dynamics may be useful for understanding the neural mechanisms that underlie the disparate cognitive and functional impairments of schizophrenia.
It is plausible that night shift work could affect breast cancer risk, possibly by melatonin suppression or circadian clock disruption, but epidemiological evidence is inconclusive.
Using serial ...questionnaires from the Generations Study cohort, we estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for breast cancer in relation to being a night shift worker within the last 10 years, adjusted for potential confounders.
Among 102,869 women recruited in 2003-2014, median follow-up 9.5 years, 2059 developed invasive breast cancer. The HR in relation to night shift work was 1.00 (95%CI: 0.86-1.15). There was a significant trend with average hours of night work per week (P = 0.035), but no significantly raised risks for hours worked per night, nights worked per week, average hours worked per week, cumulative years of employment, cumulative hours, time since cessation, type of occupation, age starting night shift work, or age starting in relation to first pregnancy.
The lack of overall association, and no association with all but one measure of dose, duration, and intensity in our data, does not support an increased risk of breast cancer from night shift work in women.
The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and ...have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS.
Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23-75 years from the Generations Study.
The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile :0.97 (95 % CI 0.51 - 1.86) for women younger than 50 years and 1.09 (0.66 - 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E/O = 1.54(0.81 - 2.92) for younger and 1.73 (1.03 - 2.90) for older women.
The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.
Breast development and hormonal changes at puberty might affect breast cancer risk, but epidemiological analyses have focussed largely on age at menarche and not at other pubertal stages.
We ...investigated associations between the timing of pubertal stages and breast cancer risk using data from a cohort study of 104,931 women (Breakthrough Generations Study, UK, 2003-2013). Pubertal variables were reported retrospectively at baseline. Breast cancer risk was analysed using Cox regression models with breast cancer diagnosis as the outcome of interest, attained age as the underlying time variable, and adjustment for potentially confounding variables.
During follow-up (mean = 4.1 years), 1094 breast cancers (including ductal carcinoma in situ) occurred. An increased breast cancer risk was associated with earlier thelarche (age when breast growth begins; HR 95% CI = 1.23 1.02, 1.48, 1 referent and 0.80 0.69, 0.93 for ≤10, 11-12 and ≥13 years respectively), menarche (initiation of menses; 1.06 0.93, 1.21, 1 referent and 0.78 0.62, 0.99 for ≤12, 13-14 and ≥15 years), regular periods (0.99 0.83, 1.18, 1 referent and 0.74 0.59, 0.92 for ≤12, 13-14 and ≥15 years) and age reached adult height (1.25 1.03, 1.52, 1 referent and 1.07 0.87, 1.32 for ≤14, 15-16 and ≥17 years), and with increased time between thelarche and menarche (0.87 0.65, 1.15, 1 referent, 1.14 0.96, 1.34 and 1.27 1.04, 1.55 for <0, 0, 1 and ≥2 years), and shorter time between menarche and regular periods (1 referent, 0.87 0.73, 1.04 and 0.66 0.50, 0.88 for 0, 1 and ≥2 years). These associations were generally similar when considered separately for premenopausal and postmenopausal breast cancer.
Breast duct development may be a time of heightened susceptibility to risk of carcinogenesis, and greater attention needs to be given to the relation of breast cancer risk to the different stages of puberty.
Background: In the past 15 years, mobile telephone use has evolved from an uncommon activity to one with > 4.6 billion subscriptions worldwide. However, there is public concern about the possibility ...that mobile phones might cause cancer, especially brain tumors. Objectives: We reviewed the evidence on whether mobile phone use raises the risk of the main types of brain tumor—glioma and meningioma—with a particular focus on the recent publication of the largest epidemiologic study yet: the 13-country Interphone Study. Discussion: Methodological deficits limit the conclusions that can be drawn from the Interphone study, but its results, along with those from other epidemiologic, biological, and animal studies and brain tumor incidence trends, suggest that within about 10-15 years after first use of mobile phones there is unlikely to be a material increase in the risk of brain tumors in adults. Data for childhood tumors and for periods beyond 15 years are currently lacking. Conclusions: Although there remains some uncertainty, the trend in the accumulating evidence is increasingly against the hypothesis that mobile phone use can cause brain tumors in adults.
Population breast screening has been implemented in the UK for over 25 years, but the size of benefit attributable to such programmes remains controversial. We have conducted the first ...individual-based cohort evaluation of population breast screening in the UK, to estimate the impact of the NHS breast screening programme (NHSBSP) on breast cancer mortality.
We followed 988 090 women aged 49-64 years in 1991 resident in England and Wales, who because of the staggered implementation of the NHSBSP, included both invited subjects and an uninvited control group. Individual-level breast screening histories were linked to individual-level mortality and breast cancer incidence data from national registers. Risk of death from breast cancer was investigated by incidence-based mortality analyses in relation to intention to screen and first round attendance. Overdiagnosis of breast cancer following a single screening round was also investigated.
Invitation to NHSBSP screening was associated with a reduction in breast cancer mortality in 1991-2005 of 21% (RR=0.79, 95% CI: 0.73-0.84, P<0·001) after adjustment for age, socioeconomic status and lead-time. Breast cancer deaths among first invitation attenders were 46% lower than among non-attenders (RR=0.54, 95% CI: 0.51-0·57, P<0.001) and 32% lower following adjustment for age, socioeconomic status and self-selection bias (RR=0.68, 95% CI: 0.63-0·73, P<0.001). There was little evidence of overdiagnosis associated with invitation to first screen.
The results indicate a substantial, statistically significant reduction in breast cancer mortality between 1991 and 2005 associated with NHSBSP activity. This is important in public health terms.
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