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Background Ovarian cancer is the fifth leading cause of cancer mortality in UK women. Ovarian cancer survival varies by disease stage at diagnosis, but evidence is mixed on the effect of tumour histological type (histotype) and other factors. Methods 1.3 million UK women completed a detailed health questionnaire in 1996–2001 and were followed for incident cancers and deaths via linkage to national databases. Using Cox regression models, we estimated adjusted relative risks (RRs) of death from ovarian cancer, by stage at diagnosis, tumour histotype, and 16 other personal characteristics of the women. Results During 17.7 years’ average follow-up, 13,222 women were diagnosed with ovarian cancer, and 8697 of them died from the disease. Stage at diagnosis was a major determinant of survival (stage IV vs I, RR=10.54, 95% CI: 9.16–12.13). Histotype remained a significant predictor after adjustment for stage and other factors, but associations varied over the follow-up period. Histotype-specific survival was worse for high-grade than low-grade tumours. Survival appeared worse with older age at diagnosis (per 5 years: RR=1.19, 95% CI: 1.15–1.22), higher BMI (per 5-unit increase: RR=1.06, 95% CI: 1.02–1.11), and smoking (current vs never: RR=1.17, 95% CI: 1.07–1.27), but there was little association with 13 other pre-diagnostic reproductive, anthropometric, and lifestyle factors. Conclusion Stage at diagnosis is a strong predictor of ovarian cancer survival, but tumour histotype and grade remain predictors of survival even after adjustment for stage and other factors, contributing further evidence of biological dissimilarity between the ovarian cancer histotypes. Obesity and smoking represent potentially-modifiable determinants of survival, but the stronger association with stage suggests that improving earlier diagnosis would have a greater impact on increasing ovarian cancer survival., Highlights • This study investigated ovarian cancer survival in a cohort of 1.3 million UK women. • After 18 years of follow-up, the study included 13,222 incident ovarian cancers. • Stage, age and histotype were significantly associated with ovarian cancer survival. • Survival was also worse with higher BMI and smoking, but with less impact than stage.

Background Hypertension has been associated with an increased risk of kidney cancer, but evidence of association with cancers elsewhere in the urinary tract is mixed. We examined the association between hypertension and the incidence of cancers of the kidney (by histotype), and urinary tract, in a large cohort of UK women. Methods Participants were recruited in 1996–2001 from 66 NHS breast-screening centres, and completed a questionnaire on anthropometric, reproductive and lifestyle factors, and medical history, including self-reported hypertension requiring treatment. They were followed for cancer and death via record linkage to national registries. We used Cox regression models to estimate relative risks (RRs) of cancers of the kidney and urinary tract, associated with self-reported hypertension requiring treatment at recruitment, adjusted for potential confounders. Analyses were conducted in Stata 15. Results In 1,319,718 women without previous cancer, 211,663 (16%) reported at recruitment that they were currently being treated for hypertension. After 16.9 years’ (SD 4.6) mean follow-up, 5391 kidney cancers, including 4248 renal cell carcinomas and 442 urothelial carcinomas, accrued. Hypertension requiring treatment at recruitment was associated with a significantly greater increase in the risk of renal cell carcinomas (RR=1.69, 95% CI: 1.57–1.82) than urothelial carcinomas of the kidney (RR=1.27, 95% CI: 1.00–1.62); heterogeneity by histotype, p=0.02. There were no clear associations between hypertension at recruitment and the risk of urothelial carcinomas elsewhere in the urinary tract (ureter: n=249, RR=0.82, 95% CI: 0.57–1.17; bladder: n=2929, RR=1.00, 95% CI: 0.91–1.11). The association seen with renal cell carcinomas persisted even after exclusion of the first 10 years of follow-up (RR=1.69, 95% CI: 1.54–1.85), suggesting it was not an artefact of reverse causation. Conclusion Hypertension is strongly associated with an increased risk of kidney cancer, with significant heterogeneity by histotype. The risk of renal cell carcinoma is substantially increased in those with a history of hypertension, but there is little or no association with urothelial carcinomas, either in the kidney or the rest of the urinary tract.

To assess directly the effects of various risk factors on lung cancer incidence among never smokers, large prospective studies are needed. In a cohort of 1.2 million UK women without prior cancer, half (634,039) reported that they had never smoked. Mean age at recruitment was 55 (SD5) years, and during 14 (SD3) years of follow-up, 0.2% (1,469) of these never smokers developed lung cancer. Cox regression was used to estimate relative risks (RRs) of lung cancer for 34 potential risk factors, of which 31 were nonsignificant (p > 0.05). The remaining three risk factors were associated with a significantly increased incidence of lung cancer in never smokers: non-white vs. white ethnicity (RR = 2.34, 95% CI 1.55-3.52, p

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

The risk of ovarian cancer is reduced in women who undergo tubal ligation. Although it has been suggested that tubal ligation is also associated with reduced risk of breast, endometrial, and cervical cancers, there is no clear evidence for these tumors. The Million Women Study is a prospective study that investigated associations for 26 site-specific cancers among 1.3 million UK women enrolled in 1996–2001. At enrollment, participants completed a questionnaire on sociodemographic, reproductive, and lifestyle factors; follow-up outcomes for cancer and death were obtained from national registries. Cox regression models were used to estimate adjusted relative risks (aRRs) of developing 26 cancer types or sites among women with and without tubal ligation. Of 1,278,783 women without previous cancer, 167,430 developed incident cancers after a mean follow-up of 13.8 years. Risks were significantly reduced in women with tubal ligation for cancers of the ovary (aRR, 80; 95% confidence interval [CI], 0.76–0.85; P < 0.001; n = 8035), peritoneum (aRR, 0.81; 95 CI%, 0.66–0.98; P = 0.03; n = 730), and fallopian tube (aRR, 0.60; 95 CI%, 0.37–0.96; P = 0.04; n = 168). There were no significant associations for cancers of the breast, endometrium, or cervix. The findings are consistent with the hypothesis that cancers of the ovary, peritoneum, and fallopian tube have a shared origin in the fallopian tube and that tubal ligation reduces cancer risk. These data, as well as findings of other investigators, suggest that the fallopian tube is a barrier to cells, carcinogens, or other agents reaching the ovary and peritoneal cavity.

Ovarian cancer risk is known to be reduced amongst women who have had children, but reported associations with breastfeeding are varied. Few studies have had sufficient power to explore reliably these associations by tumour histotype. In a prospective study of 1.1 million UK women, 8719 developed ovarian cancer during follow‐up. Cox regression yielded adjusted relative risks (RRs) overall and by tumour histotype amongst women with different childbearing patterns. Nulliparous women had a 24% greater ovarian cancer risk than women with one child, with significant heterogeneity by histotype (p = 0.01). There was no significant increase in serous tumours, a modest increase in mucinous tumours, but a substantial increase in endometrioid (RR = 1.49, 95% CI: 1.18‐1.89) and clear‐cell tumours (RR = 1.68, 1.29‐2.20). Among parous women, each additional birth was associated with an overall 6% reduction in ovarian cancer risk; this association also varied by histotype (p = 0.0006), with the largest reduction in risk for clear‐cell tumours (RR per birth = 0.75, 0.65‐0.85, p, What's new? Evidence suggests that women who bear children are at decreased risk of ovarian cancer. Whether breastfeeding contributes to this reduction in risk remains unclear. In this prospective study, each birth in parous women reduced overall ovarian cancer risk by 6%, while nulliparity was associated with a 24% increase in risk compared to women with one child. Among parous women, risk reduction varied by tumour type, with the greatest reduction observed for clear cell tumours and almost no reduction detected for serous tumours. Ovarian cancer risk was additionally reduced by 10% for every 12 months of breastfeeding.

Summary Background Excess weight is associated with poor health and increased health-care costs. However, a detailed understanding of the effects of excess weight on total hospital costs and costs for different health conditions is needed. Methods Women in England aged 50–64 years were recruited into the prospective Million Women Study cohort in 1996–2001 through 60 NHS breast cancer screening centres. Participants were followed up and annual hospital costs and admission rates were estimated for April 1, 2006, to March 31, 2011, in relation to body-mass index (BMI) at recruitment, overall and for categories of health conditions defined by the International Classification of Diseases 10th revision chapter of the primary diagnosis at admission. Associations of BMI with hospital costs were projected to the 2013 population of women aged 55–79 years in England. Findings 1 093 866 women who provided information on height and weight, had a BMI of at least 18·5 kg/m 2 , and had no previous cancer at recruitment, were followed up for an average of 4·9 years from April 1, 2006 (12·3 years from recruitment), during which time 1·84 million hospital admissions were recorded. Annual hospital costs were lowest for women with a BMI of 20·0 kg/m 2 to less than 22·5 kg/m 2 (£567 per woman per year, 99% CI 556–577). Every 2 kg/m 2 increase in BMI above 20 kg/m 2 was associated with a 7·4% (7·1–7·6) increase in annual hospital costs. Excess weight was associated with increased costs for all diagnostic categories, except respiratory conditions and fractures. £662 million (14·6%) of the estimated £4·5 billion of total annual hospital costs among all women aged 55–79 years in England was attributed to excess weight (BMI ≥25 kg/m 2 ), of which £517 million (78%) arose from hospital admissions with procedures. £258 million (39%) of the costs attributed to excess weight were due to musculoskeletal admissions, mainly for knee replacement surgeries. Interpretation Excess body weight is associated with increased hospital costs for middle-aged and older women in England across a broad range of conditions, especially knee replacement surgery and diabetes. These results provide reliable up-to-date estimates of the health-care costs of excess weight and emphasise the need for investment to tackle this public health issue. Funding Cancer Research UK; Medical Research Council; National Institute for Health Research.

Birth weight and height are correlated and likely to be markers of some aspect of growth that affects cancer risk in adulthood. However, birth weight adds little, if any, additional information to adult height as a predictor of cancer incidence in women., Background Most evidence about associations between birth weight and adult cancer risk comes from studies linking birth records to cancer registration data, where information on known risk factors for cancer is generally lacking. Here, we report on associations between birth weight and cause-specific cancer risk in a large cohort of UK women, and investigate how observed associations are affected by other factors. Methods A total of 453 023 women, born in the 1930s and 1940s, reported their birth weight, maternal smoking, parental heights, age at menarche, adult height, adult smoking, and many other personal characteristics. They were followed for incident cancer. Using Cox regression, relative risks by birth weight were estimated for cancers with more than 1500 incident cases, adjusting for 17 potential confounding factors, individually and simultaneously. Results Birth weight reported in adulthood was strongly correlated with that recorded at birth (correlation coefficient = 0.78, P < 0.0001). Reported birth weight was associated with most of the potential confounding factors examined, the strongest association being with adult height. After 9.2 years follow-up per woman, 39 060 incident cancers were registered (4414 colorectal, 3175 lung, 1795 malignant melanoma, 14 542 breast, 2623 endometrial, 2009 ovarian, 1565 non-Hodgkin lymphoma, and 8937 other cancers). Associations with birth weight were null or weak and reduced after adjustment by adult height (P[trend] > 0.01 for every cancer, after adjustment). In contrast, adult height was strongly related to the risk of every cancer except lung cancer, after adjusting for birth weight and other factors (P[trend] < 0.0001 for most cancers). For lung cancer, adjusting for smoking reduced the association with birth weight. Meta-analyses were dominated by our findings. Conclusion Birth weight and adult height are correlated and likely to be markers of some aspect of growth that affects cancer risk in adulthood. However, birth weight adds little, if any, additional information to adult height as a predictor of cancer incidence in women.

Background Results from some retrospective studies suggest a possible increased risk of glioma and acoustic neuroma in users of mobile phones. Methods The relation between mobile phone use and incidence of intracranial central nervous system (CNS) tumours and other cancers was examined in 791,710 middle-aged women in a UK prospective cohort, the Million Women Study. Cox regression models were used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Women reported mobile phone use in 1999 to 2005 and again in 2009. Results During 7 years' follow-up, 51,680 incident invasive cancers and 1,261 incident intracranial CNS tumours occurred. Risk among ever vs never users of mobile phones was not increased for all intracranial CNS tumours (RR = 1.01, 95% CI = 0.90-1.14, P = 0.82), for specified CNS tumour types nor for cancer at 18 other specified sites. For long-term users compared with never users, there was no appreciable association for glioma (10+ years: RR = 0.78, 95% CI = 0.55-1.10, P = 0.16) or meningioma (10+ years: RR = 1.10, 95% CI = 0.66-1.84, P = 0.71). For acoustic neuroma, there was an increase in risk with long term use vs never use (10+ years: RR = 2.46, 95% CI = 1.07-5.64, P = 0.03), the risk increasing with duration of use (trend among users, P = 0.03). Conclusions In this large prospective study, mobile phone use was not associated with increased incidence of glioma, meningioma or non-CNS cancers.

0.86 (0.75–0.99) 1.01 (0.82–1.25) 1.19 (0.81–1.75)

Little is known about the etiology of in situ ductal breast cancer (DCIS) or what influences its possible progression to invasive ductal disease. Comparison of risk factors for DCIS and invasive ductal cancer may throw some light on these issues. We estimated relative risks for DCIS and invasive ductal breast cancer according to 12 genetic and eight environmental risk factors among 1.1 million postmenopausal women in a large prospective UK study. There was no strong evidence of a different association with DCIS versus invasive ductal cancer for any of the 12 susceptibility loci examined. We also found similar associations of age at menarche, age at first birth, parity, age at menopause, family history of breast cancer and use of hormone replacement therapy with DCIS and invasive ductal cancer. Only body mass index (BMI) showed a clear difference in association in that it was positively associated with the risk of invasive ductal cancer but not DCIS (RRs per 5 kg/m(2) = 1.20 and 1.01, respectively; p-value for heterogeneity = 0.002). The very similar risk factor profiles observed here for DCIS and invasive ductal cancer suggest that DCIS is a precursor of invasive ductal cancer and most risk factors affect the risk of invasive ductal cancer primarily through their effects on the risk of DCIS. The lack of association between BMI and DCIS suggests a greater influence of BMI on disease progression.

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case-control study of breast cancer in women aged 36-45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk (RR) of 1.12 (95% confidence interval (CI) 0.72-1.73) for past smokers and RR of 1.19 (95% CI 0.72-1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 (95% CI 0.64-1.25), in past smokers, RR of 1.09 (95% CI 0.75-1.56), or in current smokers, RR of 0.93 (95% CI 0.67-1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.

BACKGROUND: Greater adiposity and height have been associated with increased risk of haematological malignancies. Associations for disease subtypes are uncertain. METHODS: A cohort of 1.3 million middle-aged U.K. women was recruited in 1996-2001 and followed for 10 years on average. Potential risk factors were assessed by questionnaire. Death, emigration, and incident cancer were ascertained by linkage to national registers. Adjusted relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162 participants were diagnosed with lymphatic or haematopoietic cancers. Each 10 kg m(-2) increase in body mass index was associated with relative risk of 1.20 (95% confidence interval: 1.13-1.28) for lymphoid and 1.37 (1.22-1.53) for myeloid malignancy (P=0.06 for heterogeneity); similarly, Hodgkin lymphoma 1.64 (1.21-2.21), diffuse large B-cell lymphoma 1.36 (1.17-1.58), plasma cell neoplasms 1.21 (1.06-1.39), acute myeloid leukaemia 1.47 (1.19-1.81), and myeloproliferative/myelodysplastic syndromes 1.32 (1.15-1.52). Each 10 cm increase in height was associated with relative risk of 1.21 (1.16-1.27) for lymphoid and 1.11 (1.02-1.21) for myeloid malignancy (P=0.07 for heterogeneity); similarly, mature T-cell malignancies 1.36 (1.03-1.79), diffuse large B-cell lymphoma 1.28 (1.14-1.43), follicular lymphoma 1.28 (1.13-1.44), plasma cell neoplasms 1.12 (1.01-1.24), chronic lymphocytic leukaemia/small lymphocytic lymphoma 1.23 (1.08-1.40), and acute myeloid leukaemia 1.22 (1.04-1.42). There was no significant heterogeneity between subtypes. CONCLUSION: In middle-aged women, greater body mass index and height were associated with modestly increased risks of many subtypes of haematological malignancy.

Summary Background Women born around 1940 in countries such as the UK and USA were the first generation in which many smoked substantial numbers of cigarettes throughout adult life. Hence, only in the 21st century can we observe directly the full effects of prolonged smoking, and of prolonged cessation, on mortality among women in the UK. Methods For this prospective study, 1·3 million UK women were recruited in 1996–2001 and resurveyed postally about 3 and 8 years later. All were followed to Jan 1, 2011, through national mortality records (mean 12 woman-years, SD 2). Participants were asked at entry whether they were current or ex-smokers, and how many cigarettes they currently smoked. Those who were ex-smokers at both entry and the 3-year resurvey and had stopped before the age of 55 years were categorised by the age they had stopped smoking. We used Cox regression models to obtain adjusted relative risks that compared categories of smokers or ex-smokers with otherwise similar never-smokers. Findings After excluding 0·1 million women with previous disease, 1·2 million women remained, with median birth year 1943 (IQR 1938–46) and age 55 years (IQR 52–60). Overall, 6% (66 489/1 180 652) died, at mean age 65 years (SD 6). At baseline, 20% (232 461) were current smokers, 28% (328 417) were ex-smokers, and 52% (619 774) were never-smokers. For 12-year mortality, those smoking at baseline had a mortality rate ratio of 2·76 (95% CI 2·71–2·81) compared with never-smokers, even though 44% (37 240/85 256) of the baseline smokers who responded to the 8-year resurvey had by then stopped smoking. Mortality was tripled, largely irrespective of age, in those still smoking at the 3-year resurvey (rate ratio 2·97, 2·88–3·07). Even for women smoking fewer than ten cigarettes per day at baseline, 12-year mortality was doubled (rate ratio 1·98, 1·91–2·04). Of the 30 most common causes of death, 23 were increased significantly in smokers; for lung cancer, the rate ratio was 21·4 (19·7–23·2). The excess mortality among smokers (in comparison with never-smokers) was mainly from diseases that, like lung cancer, can be caused by smoking. Among ex-smokers who had stopped permanently at ages 25–34 years or at ages 35–44 years, the respective relative risks were 1·05 (95% CI 1·00–1·11) and 1·20 (1·14–1·26) for all-cause mortality and 1·84 (1·45–2·34) and 3·34 (2·76–4·03) for lung cancer mortality. Thus, although some excess mortality remains among these long-term ex-smokers, it is only 3% and 10% of the excess mortality among continuing smokers. If combined with 2010 UK national death rates, tripled mortality rates among smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference. Interpretation Among UK women, two-thirds of all deaths of smokers in their 50s, 60s, and 70s are caused by smoking; smokers lose at least 10 years of lifespan. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater. Stopping before age 40 years (and preferably well before age 40 years) avoids more than 90% of the excess mortality caused by continuing smoking; stopping before age 30 years avoids more than 97% of it. Funding Cancer Research UK, Medical Research Council.

Hip fracture risk is known to increase with physical inactivity and decrease with obesity, but there is little information on their combined effects. We report on the separate and combined effects of body mass index (BMI) and physical activity on hospital admissions for hip fracture among postmenopausal women in a large prospective UK study. Baseline information on body size, physical activity, and other relevant factors was collected in 1996-2001, and participants were followed for incident hip fractures by record linkage to National Health Service (NHS) hospital admission data. Cox regression was used to calculate adjusted relative risks of hip fracture. Among 925,345 postmenopausal women followed for an average of 6.2 years, 2582 were admitted to hospital with an incident hip fracture. Hip fracture risk increased with decreasing BMI: Compared with obese women (BMI of 30+ kg/m2), relative risks were 1.71 [95% confidence interval (CI) 1.47-1.97)] for BMI of 25.0 to 29.9 kg/m2 and 2.55 (95% CI 2.22-2.94) for BMI of 20.0 to 24.9 kg/m2. The increase in fracture risk per unit decrease in BMI was significantly greater among lean women than among overweight women (pa

We examined the relation between the use of hormone replacement therapy (HRT) and the incidence of central nervous system (CNS) tumours in a large prospective study of 1,147,894 postmenopausal women. Women were aged 56.6 years on average at entry, and HRT use was recorded at recruitment and updated, where possible, about 3 years later. During a mean follow-up of 5.3 years per woman, 1,266 CNS tumours were diagnosed, including 557 gliomas, 311 meningiomas and 117 acoustic neuromas. Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). In past users of HRT the relative risk was 1.07 (95% CI: 0.93-1.24) for all CNS tumours. Among current users of HRT, there was significant heterogeneity by the type of HRT with the users of oestrogen-only HRT at higher risk of all CNS tumours than users of oestrogen-progestagen HRT (RR = 1.42, 95% CI: 1.21-1.67 versus RR = 0.97, 95% CI: 0.82-1.16) (heterogeneity p < 0.001). Among current users of oestrogen-only and oestrogen-progestagen HRT, there was no significant heterogeneity by duration of use, hormonal constituent or mode of administration of HRT.

Background: The relationship between cigarette smoking and incidence of acoustic neuromas and pituitary tumours is uncertain. Methods: We examined the relation between smoking and risk of acoustic neuromas and pituitary tumours in a prospective study of 1.2 million middle-aged women in the United Kingdom. Results: Over 10.2 million person years of follow-up, 177 women were diagnosed with acoustic neuromas and 174 with pituitary tumours. Current smokers at recruitment were at significantly reduced risk of incident acoustic neuroma compared with never smokers (adjusted relative risk (RR)=0.41, 95% confidence interval (CI)=0.24–0.70, P=0.001). Past smokers did not have significantly different risk of acoustic neuroma than never smokers (RR=0.87, 95% CI=0.62–1.22, P=0.4). Smoking was not associated with incidence of pituitary tumours (RR in current vs never smokers=0.91, 95% CI=0.60–1.40, P=0.7). Conclusion: Women who smoke are at a significantly reduced risk of acoustic neuromas, but not of pituitary tumours, compared with never smokers. Acoustic neuromas are much rarer than the cancers that are increased among smokers.

There is inconsistent evidence about the effect of reproductive history on women's risk of pancreatic cancer. In the Million Women Study, a prospective cohort of middle-aged women in the United Kingdom, we examined associations between reproductive history and pancreatic cancer incidence and mortality, controlling for age, socioeconomic status, geographic region, body mass index, smoking, and history of diabetes. During 7.1 million person-years of follow-up in 995,192 postmenopausal women, there were 1,182 incident pancreatic cancers. Pancreatic cancer incidence and mortality did not vary significantly with age at menarche, number of children, age at first birth, breast-feeding, type of menopause, age at menopause, or time since menopause. Any effect of reproductive history and pancreatic cancer risk in women is likely to be weak, if it exists at all. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1457–60)

Women with a family history of breast cancer have an increased risk of the disease. However, since they tend to experience greater surveillance for the disease, their breast cancers may be detected at an earlier stage, thus making it difficult to assess reliably whether tumour characteristics vary by family history. Information on 9,731 Million Women Study participants with screen-detected breast cancer, diagnosed in 1996-2003, and 37,983 matched controls, who also attended routine screening but were not diagnosed with breast cancer, was used to estimate adjusted relative risks (RRs) of screen-detected breast cancer in women with a family history of the disease. Women with a family history of breast cancer had an increased risk of screen-detected breast cancer (RR 1.57; 95% CI:1.47-1.68) compared with those without such a family history. The RRs were 1.58 (1.46-1.71) and 1.55 (1.34-1.80) for invasive and in situ breast cancer; 1.63 (1.49-1.79) and 1.55 (1.32-1.83) for node-negative and node-positive disease; and 1.56 (1.42-1.70), 1.75 (1.39-2.21) and 1.71 (1.28-2.29) for ductal, lobular and tubular cancers. There was no significant difference in the RR of screen-detected breast cancer associated with a family history of the disease according to invasiveness, size, nodal status, malignancy grade or morphological type of the breast cancer.

Previous studies have reported inconsistent results on the effect of anthropometric and lifestyle factors on the risk of developing glioma or meningioma tumours. A prospective cohort of 1.3 million middle-aged women was used to examine these relationships. During 7.7 million women-years of follow-up, a total of 1563 women were diagnosed with a primary incident central nervous system tumour: 646 tumours were classified as glioma and 390 as meningioma. Our results show that height is related to the incidence of all central nervous system tumours with a risk of about 20% per 10 cm increase in height (relative risk=1.19, 95% CI=1.10-1.30 per 10 cm increase in height, P

Background Active smoking has little or no effect on women's risk of developing breast cancer, but it has been suggested that passive exposure to tobacco smoke may increase this risk among women who have never smoked. Objective To evaluate the possible relationship between passive smoking and breast cancer risk within the Million Women Study, a large UK prospective study, and to report a meta-analysis of published results. Methods In the large prospective study, 224 917 never smokers who completed a questionnaire that asked women whether their parents had smoked and if their current partner smoked were followed up for an average of 3.5 years for incident breast cancer. In the meta-analysis, studies that had recorded exposure information prospectively and retrospectively were considered separately. Main outcome measures Adjusted relative risk of breast cancer in never smokers who were passively exposed to tobacco smoke at various ages compared with never smokers with no such exposure. Results In the prospective study, 2518 incident invasive breast cancers occurred during follow-up and the adjusted relative risk of breast cancer for passive exposure either as a child or as an adult vs neither exposure was 0.98 (95% CI 0.88-1.09); results were similarly null for childhood exposure (0.98, 0.88-1.08) and adult exposure (1.02, 0.89-1.16) separately. We identified seven other studies with prospectively recorded exposure data; when results of all eight studies were combined (including 5743 never smokers with breast cancer), the aggregate relative risk was 0.99 (0.93-1.05) for any passive exposure. The aggregate findings differed substantially (P = 0.0002) between these 8 studies and 17 other studies with retrospectively recorded information (including 5696 never smokers with breast cancer). Conclusions Aggregate results from studies with prospectively reported information show that the incidence of breast cancer is similar in women who did and did not report passive exposure to tobacco smoke either as a child or as an adult. The aggregate findings from the retrospective studies may have been distorted by some women becoming more likely to report past exposures because they knew that they had breast cancer.

To compare the effect of potentially modifiable lifestyle factors on the incidence of vascular disease in women with and without diabetes. In 1996-2001 over one million middle-aged women in the UK joined a prospective study, providing medical history, lifestyle and socio-demographic information. All participants were followed for hospital admissions and deaths using electronic record-linkage. Adjusted relative risks (RRs) and incidence rates were calculated to compare the incidence of coronary heart disease and stroke in women with and without diabetes and by lifestyle factors. At recruitment 25,915 women (2.1% of 1,242,338) reported current treatment for diabetes. During a mean follow-up of 6.1 years per woman, 21,928 had a first hospital admission or death from coronary heart disease (RR for women with versus without diabetes = 3.30, 95% CI 3.14-3.47) and 7,087 had a first stroke (RR = 2.47, 95% CI 2.24-2.74). Adjusted incidence rates of these conditions in women with diabetes increased with duration of diabetes, obesity, inactivity and smoking. The 5-year adjusted incidence rates for cardiovascular disease were 4.6 (95% CI 4.4-4.9) per 100 women aged 50-69 in non-smokers with diabetes, 5.9 (95% CI 4.6-7.6) in smokers with diabetes not using insulin and 11.0 (95% CI 8.3-14.7) in smokers with diabetes using insulin. Non-smoking women with diabetes who were not overweight or inactive still had threefold increased rate for coronary disease or stroke compared with women without diabetes. Of the modifiable factors examined in middle aged women with diabetes, smoking causes the greatest increase in cardiovascular disease, especially in those with insulin treated diabetes.

OBJECTIVE: To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. DESIGN: Prospective cohort study. PARTICIPANTS: 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. MAIN OUTCOME MEASURES: Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. RESULTS: 45,037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. CONCLUSIONS: Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.

Background Reports of the association between breastfeeding and ovarian cancer are inconsistent, and few studies have been able to explore possible heterogeneity by histological subtype. Methods We used data from the Million Women Study, a prospective study of UK women. Participants were recruited in 1996–2001 at breast-screening invitation, and completed a questionnaire on various exposures, including breastfeeding. Follow-up was via routinely-collected cancer registry data. Using Cox regression models, we estimated adjusted relative risks of ovarian cancer amongst women who breastfed compared to women who had not, and by average duration of breastfeeding per child. All analyses were restricted to parous women, stratified by parity (1, 2, 3+), and adjusted for ten potential confounding factors. We used a competing risks approach to explore variation by histological subtype. Analyses were conducted using STATA-13. Results After excluding nulliparous women and those with bilateral oophorectomy or unknown breastfeeding, the study population included 813,035 women. There were 5026 incident cases of ovarian cancer, after a mean follow-up of 12.9 years. 553,624 (68%) of the women reported breastfeeding (median duration: 2 months per child; IQR: 1–5 months). Overall, the relative risk of ovarian cancer was not significantly different amongst women who breastfed compared to women who had not (RR: 0.94, 95% CI: 0.89–1.00, p = 0.07). However, there was strong evidence that this varied by duration of breastfeeding. Women who breastfed for Conclusion Our results provide strong evidence of a reduced risk of ovarian cancer amongst women who breastfed for ≥6 months/child. Our results are in keeping with those from other epidemiological studies, but emphasise the importance of longer durations of breastfeeding. We found no evidence of significant heterogeneity by histological subtype. On behalf of the Million Women Study Collaborators.

Background Systematic reviews have found few differences in nutrient content between organic and conventional crops, but organic foods are less likely to contain pesticide residues. Pesticide exposure has been linked to a possible increased risk of certain cancer sites, including soft tissue sarcoma, breast cancer, and non-Hodgkin lymphoma. We examined the hypothesis that eating organic food may reduce the risk of cancer in a large prospective study of women. Methods The study participants included 623,080 middle-aged UK women with no prior cancer and who had not changed their diet due to illness in the last five years. Women reported their consumption of organic food in 2002, and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks by the reported frequency of consumption of organic foods for 17 specific sites or types of cancer and for total cancer. Results At baseline, 30%, 63% and 7% of women reported never, sometimes or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n = 53,769 cases in total) (RR for usually/always versus never = 1.03, 95% CI: 0.99–1.07), soft tissue sarcoma (RR = 1.37, 95% CI: 0.82–2.27), or breast cancer (RR = 1.09, 95% CI: 1.02–1.15), but was for non-Hodgkin lymphoma (RR = 0.79, 95% CI: 0.65–0.96). Conclusion In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.

Background A protective association between parity and ovarian cancer has been reported by many investigators. Some have reported heterogeneity of the association by histological subtype, but few studies have enough cases to explore this fully. Methods We used data from the Million Women Study, a prospective cohort of middle-aged women in the UK. Participants were recruited in 1998 on average when they were invited for routine breast screening, and completed a questionnaire on a range of exposures, including the number of children they had had. Follow-up was via routinely-collected data from central cancer registries. Using Cox regression models, we estimated adjusted relative risks of ovarian cancer amongst parous women compared to nulliparous women, and per birth amongst parous women, adjusted by nine potential confounding factors. We used a competing risks approach to explore variation by histological subtype. All analyses were conducted using STATA 13. Results After excluding those with bilateral oophorectomy and unknown parity, the study population included 1.1 million women. There were 6952 incident cases of ovarian cancer, after a mean follow-up of 12.2 years. Overall, parous women had a 26% lower risk of ovarian cancer than nulliparous women (RR: 0.74, 95% CI: 0.69–0.79), but there was significant heterogeneity by histological subtype (p-het=0.0002). The reduced risk appeared to be significantly stronger for endometrioid (n = 631, RR: 0.57, 95% CI: 0.46–0.69) and clear cell tumours (n = 343, RR: 0.46, 95% CI: 0.36–0.60) than for serous tumours (n = 2912, RR: 0.84, 95% CI: 0.75–0.94). Amongst parous women, each additional birth was associated with a 6% reduction in relative risk of ovarian cancer (RR-per-birth: 0.94, 95% CI: 0.91–0.96); there was no significant heterogeneity by tumour subtype. Conclusion We have strong evidence that the reduced risk of ovarian cancer in parous women varies by histological subtype. Our results are in keeping with those from other epidemiological studies, and are consistent with findings from histopathological and genetic studies, which suggest that the different subtypes of ovarian cancer have different aetiologies. The greater degree of heterogeneity by subtype when comparing parous vs nulliparous women, than for increasing parity amongst parous women, may suggest the influence of infertility.

Approximately 4300 people are diagnosed with a brain or other central nervous system (CNS) tumour annually in the UK. They have poor prognosis, yet little is known about risk factors of the tumours. To investigate the role of hormone replacement therapy (HRT) and the risk of brain and …

Although much is known about the effects of smoking, there is limited reliable information on the effects of stopping smoking on mortality. To investigate the association between stopping smoking and the risk of all-cause mortality and of cause specific mortality, including deaths due to cancer and vascular disease. In particular, to investigate how the risks for former smokers compare with those of lifelong non-smokers as the period of time …