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Background The ongoing debate of whether use of cellular telephones increases the risk of developing a brain tumor was recently fueled by the launch of the fifth generation of wireless technologies. Here, we update follow-up of a large-scale prospective study on the association between cellular telephone use and brain tumors. Methods During 1996-2001, 1.3 million women born in 1935-1950 were recruited into the study. Questions on cellular telephone use were first asked in median year 2001 and again in median year 2011. All study participants were followed via record linkage to National Health Services databases on deaths and cancer registrations (including nonmalignant brain tumors). Results During 14 years follow-up of 776 156 women who completed the 2001 questionnaire, a total of 3268 incident brain tumors were registered. Adjusted relative risks for ever vs never cellular telephone use were 0.97 (95% confidence interval = 0.90 to 1.04) for all brain tumors, 0.89 (95% confidence interval = 0.80 to 0.99) for glioma, and not statistically significantly different to 1.0 for meningioma, pituitary tumors, and acoustic neuroma. Compared with never-users, no statistically significant associations were found, overall or by tumor subtype, for daily cellular telephone use or for having used cellular telephones for at least 10 years. Taking use in 2011 as baseline, there were no statistically significant associations with talking for at least 20 minutes per week or with at least 10 years use. For gliomas occurring in the temporal and parietal lobes, the parts of the brain most likely to be exposed to radiofrequency electromagnetic fields from cellular telephones, relative risks were slightly below 1.0. Conclusion Our findings support the accumulating evidence that cellular telephone use under usual conditions does not increase brain tumor incidence.

Background Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Methods and findings Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case–control study for 9,498 women aged Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. Conclusions This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.

Background: Social isolation has been associated with increased risks of coronary heart disease (CHD) and stroke. It is unclear, however, whether the associations differ between fatal and non-fatal events or by the type of isolation (living alone or having few social contacts). We examined these associations in two large UK prospective studies. Methods: Overall 481,946 Million Women Study and 456,612 UK Biobank participants without prior CHD or stroke were followed by electronic-linkage to national hospital and death records. Cox regression yielded adjusted risk ratios (RRs) for first CHD and stroke (separately for deaths without prior hospital admission and for hospital admission as the first event) by three levels of social isolation (based on living alone, contact with family/friends, and group participation). Results: In the two studies combined, there were 42,402 first CHD and 19,999 first stroke events during 7 (SD=2) years follow-up/participant. Social isolation showed little, if any, association with hospital admissions as the first CHD or stroke events. Risks were substantially elevated, however, in the most versus least isolated group if the first event was death without prior hospital admission: RR=1.86 (95% CI 1.63-2.12) for CHD and RR=1.91 (95% CI 1.48-2.46) for stroke. For CHD or stroke death as the first event, RRs were significantly greater (p=0.002) for those living alone versus not (RR=1.60, 95% CI 1.46-1.75) than for those with few versus more social contacts (1.27, 95% CI 1.16-1.38). Results did not differ between studies, or by self-rated health. Conclusion: Social isolation appears to have little direct effect on the risk of developing a first non-fatal CHD or stroke. By contrast, isolation substantially increases the risk that the first such event is fatal, particularly among those living alone, perhaps because of the lack of immediate help in responding to an acute CHD or acute stroke.

Background: Participation in social activities is thought to prevent heart disease, but evidence is inconclusive. Design: We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women. Methods: Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities. Results: After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81–0.86), but changed to 1.06 (99% confidence interval 1.02–1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations. Conclusions: Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants.

About 1 in 10 postmenopausal UK women are currently prescribed oral bisphosphonates, but there are concerns about their adverse effects. Osteonecrosis of the jaw is a recognised uncommon but important side effect of intravenous bisphosphonates, but epidemiological evidence on risk of osteonecrosis of the jaw associated with oral bisphosphonate use is less conclusive. The incidence of hospital admission with osteonecrosis of the jaw was examined among 521,695 Million Women Study participants, aged 64.7 years at baseline. Cox proportional hazards regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) associated with use of oral bisphosphonates in postmenopausal women followed-up by record-linkage to National Health Service hospital admission databases. During mean follow-up of 8.2 years per woman, 100 women were admitted to hospital with first recorded osteonecrosis of the jaw, at mean age 72.4 years. Almost a third (29/100) of the cases had ever-used oral bisphosphonates. Ever-users had a six-fold increased risk of hospital admission for osteonecrosis of the jaw, when compared with never-users (adjusted RR = 6.09, 95% CI 3.83-9.66; p 0.0001). The relative risk for osteonecrosis of the jaw in never-users of oral bisphosphonates was increased in women with prior cancer (RR = 3.40, 2.22-5.22, p 0.0001). The estimated absolute risk of hospital admission for osteonecrosis of the jaw over a 5-year period from age 70 to 74 in women without prior cancer was 0.09 per 1000 in never-users and 0.69 per 1000 in ever-users of oral bisphosphonates. In this UK population of postmenopausal women, use of oral bisphosphonates was associated with a 6-fold increased risk of hospital admission with osteonecrosis of the jaw, accounting for around one-third of cases, with an excess risk of about 0.6/1000 users over 5 years.

Background:Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies. Methods:Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by

Background In 2006, the Bowel Cancer Screening Programme (BCSP) in England began offering biennial faecal occult blood testing (FOBt) at ages 60–69 years. Although FOBt is aimed at detecting colorectal neoplasms, other conditions can affect the result. In a large UK prospective study, we examined associations, both before and after screening, between FOBt positivity and 10 conditions that are often associated with gastrointestinal bleeding. Methods By electronically linking BCSP and Million Women Study records, we identified 604 495 women without previous colorectal cancer who participated in their first routine FOBt screening between 2006 and 2012. Regression models, using linked national hospital admission records, yielded adjusted relative risks (RRs) in FOBt-positive versus FOBt-negative women for colorectal cancer, adenoma, diverticular disease, inflammatory bowel disease, haemorrhoids, upper gastrointestinal cancer, oesophagitis, peptic ulcer, anaemia and other haematological disorders. Results RRs in FOBt-positive versus FOBt-negative women were 201.3 (95% CI 173.8–233.2) for colorectal cancer and 197.9 (95% CI 180.6–216.8) for adenoma within 12 months after screening and 3.49 (95% CI 2.31–5.26) and 4.88 (95% CI 3.80–6.26), respectively, 12–24 months after screening; P

Faecal occult blood (FOB) ‐ based screening programmes for colorectal cancer detect about half of all cancers. Little is known about individual health behavioural characteristics which may be associated with screen‐detected and interval cancers. Electronic linkage between the UK National Health Service Bowel Cancer Screening Programme (BCSP) in England, cancer registration and other national health records, and a large on‐going UK cohort, the Million Women Study, provided data on 628,976 women screened using a guaiac‐FOB test (gFOBt) between 2006 and 2012. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by logistic and Cox regression for associations between individual lifestyle factors and risk of colorectal tumours. Among screened women, 766 were diagnosed with screen‐detected colorectal cancer registered within 2 years after a positive gFOBt result, and 749 with interval colorectal cancers registered within 2 years after a negative gFOBt result. Current smoking was significantly associated with risk of interval cancer (RR 1.64, 95%CI 1.35–1.99) but not with risk of screen‐detected cancer (RR 1.03, 0.84–1.28), and was the only factor of eight examined to show a significant difference in risk between interval and screen‐detected cancers (p for difference, 0.003). Compared to screen‐detected cancers, interval cancers tended to be sited in the proximal colon or rectum, to be of non‐adenocarcinoma morphology, and to be of higher stage.

Reported associations between coffee consumption and an increased risk of pancreatic cancer could be due to residual confounding by smoking and/or biased recall of coffee consumption in retrospective studies. Studying associations prospectively in never smokers should minimise these problems, but thus far such studies have included relatively small numbers of cases. In this study, 309,797 never‐smoking women self‐reported typical daily coffee consumption at a mean age of 59.5 years (SD 5.0 years) and were followed up for a median of 13.7 years (IQR: 12.2‐14.9) through record linkage to national health cancer and death registries. During this period, 962 incident cases of pancreatic cancers were registered. Cox regression was used to calculate adjusted relative risks [RRs] of incident pancreatic cancer with 95% confidence intervals [CIs] in relation to coffee consumption at baseline. After adjustment for potential confounding factors, including body mass index and alcohol consumption, RRs of pancreatic cancer in never‐smokers who reported usually consuming 1‐2, 3‐4, and ≥5 cups of coffee daily, compared to non‐drinkers of coffee, were 1.02 (CI 0.83–1.26), 0.96 (0.76–1.22), and 0.87 (0.64–1.18), respectively (trend p=0.2). A meta‐analysis of results from this cohort and 3 smaller prospective studies found little or no statistically significant association between coffee consumption and pancreatic cancer risk in never smokers (summary RR=1.00, CI 0.86‐1.17 for ≥2 versus zero cups of coffee per day).

Background The role of diet in breast cancer aetiology is unclear; recent studies have suggested associations may differ by estrogen receptor status. Methods Baseline diet was assessed in 2000–04 using a validated questionnaire in 691 571 postmenopausal UK women without previous cancer, who had not changed their diet recently. They were followed by record linkage to national cancer and death databases. Cox regression yielded adjusted relative risks for breast cancer for 10 food items and eight macronutrients, subdivided mostly into five categories of baseline intake. Trends in risk across the baseline categories were calculated, assigning re-measured intakes to allow for measurement error and changes in intake over time; P-values allowed for multiple testing. Results Women aged 59.9 (standard deviation (SD 4.9)) years at baseline were followed for 12 (SD 3) years; 29 005 were diagnosed with invasive breast cancer. Alcohol intake had the strongest association with breast cancer incidence: relative risk (RR) 1.08 [99% confidence interval (CI) 1.05–1.11] per 10 g/day higher intake, P = 5.8 × 10−14. There were inverse associations with fruit: RR 0.94 (99% CI 0.92–0.97) per 100 g/day higher intake, P = 1.1 × 10−6, and dietary fibre: RR 0.91 (99% CI 0.87–0.96) per 5 g/day increase, P = 1.1 × 10−4. Fruit and fibre intakes were correlated (ρ = 0.62) and were greater among women who were not overweight, so residual confounding cannot be excluded. There was no heterogeneity for any association by estrogen receptor status. Conclusions By far the strongest association was between alcohol intake and an increased risk of breast cancer. Of the other 17 intakes examined, higher intakes of fruit and fibre were associated with lower risks of breast cancer, but it is unclear whether or not these associations are causal.

Introduction Published findings on the associations between smoking and the incidence of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are inconsistent. We aimed to generate prospective evidence on these relationships, overall and by anatomical site. Methods We followed 1,223,626 women without prior cancer by electronic linkage to national cancer registration data. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. Cox regression yielded adjusted relative risks (RRs) comparing smokers versus never-smokers. Results After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR=1.22, 95%CI 1.15-1.31) but BCC incidence was decreased (RR=0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and 7 other prospective studies were largely dominated by the findings in this study. Conclusion Smoking-associated risks for cutaneous SCC and BCC are opposite to each other, and may vary by anatomical site.

Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17‐1.51, for BMI 35+ vs, What's new? Previous research has found a link between obesity and adult lymphoid malignancy risk. In this paper, the researchers report on the relative importance of body size not only at the time of diagnosis, but also at birth, childhood, and age 20. They collected data from more than 750,000 women followed up for a period of 11 years. They showed that BMI at the time of diagnosis was the strongest determinant of risk. Being overweight at age 20 also conferred a small additional risk of lymphoid malignancy. There was comparably little evidence to support an additional role of body size at birth or childhood.

Objective: To compare associations of behavioural and related factors for incident subarachnoid and intracerebral haemorrhage and ischaemic stroke. Methods: 712,433 Million Women Study participants without prior stroke, heart disease or cancer reported behavioural and related factors at baseline (1999-2007) and were followed by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed using chi-squared tests. Where appropriate, meta-analyses were done of published prospective studies. Results: After 12.9 (SD 2.6) years follow-up, 8128 women had an incident ischaemic stroke, 2032 intracerebral haemorrhage and 1536 subarachnoid haemorrhage. In women with diabetes, risk of ischaemic stroke was substantially increased (RR=2.01; 95% CI 1.84-2.20), intracerebral haemorrhage slightly increased (RR=1.31; 1.04-1.65) but subarachnoid haemorrhage reduced (RR=0.43; 0.26-0.69) (heterogeneity by stroke type, pConclusions: Classic risk factors for stroke have considerably different effects on the three main pathological types of stroke.

BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors.METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy.FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p