A comparative analysis of risk factor associations with interval and screen-detected breast cancers: A large UK prospective study.

The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen-detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03-1.11) than screen-detected cancer (RR 1.27, 1.23-1.30); having a first-degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68-1.95) than screen-detected cancer (RR 1.52, 1.43-1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72-1.99) than screen-detected cancer (RR 1.34, 1.26-1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity.

Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies.

BACKGROUND: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. METHODS: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. RESULTS: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. CONCLUSIONS: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

Alcohol consumption and cancer incidence in women: interaction with smoking, body mass index and menopausal hormone therapy.

BACKGROUND: Alcohol consumption has been associated with increased risks of certain site-specific cancers and decreased risks of some other cancers. There is, however, little reliable evidence as to whether the alcohol-associated risks for specific cancers are modified by smoking, body mass index (BMI) and menopausal hormone therapy (MHT) use. METHODS: In the prospective UK Million Women Study, 1,233,177 postmenopausal women without prior cancer, mean age 56 (SD 5) years, reported their alcohol consumption in median year 1998 (IQR 1998-1999), and were followed by record-linkage for incident cancer. 438,056 women who drank no alcohol or < 1 drink/week were excluded. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CIs) for 21 cancers by alcohol amount; statistical significance of interactions with smoking, BMI and MHT use was assessed after allowing for multiple testing. RESULTS: In 795,121 participants, mean consumption was 6.7 (SD 6.4) alcoholic drinks/week. During 17 (SD 5) years of follow-up, 140,203 incident cancers were recorded. There was strong evidence for a substantial association between alcohol intake and risk of upper aero-digestive cancers (oesophageal squamous cell carcinoma, oral cavity, pharynx and larynx; RR per 1 drink/day = 1.38 [95% CI 1.31-1.46]). There was also strong evidence for more moderate positive associations with breast, colorectal and pancreatic cancer (RRs per 1 drink/day = 1.12 [1.10-1.14], 1.10 [1.07-1.13], 1.08 [1.02-1.13] respectively), and moderate negative associations with thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma (RRs per 1 drink/day = 0.79 [0.70-0.89], 0.91 [0.86-0.95], 0.88 [0.83-0.94], 0.90 [0.84-0.97] respectively). Significant interactions between alcohol and smoking were seen for upper aero-digestive cancers (RRs per 1 drink/day = 1.66 [1.54-1.79], 1.23 [1.11-1.36], 1.12 [1.01-1.25] in current, past, and never smokers respectively). BMI and MHT did not significantly modify any alcohol-associated risks. CONCLUSIONS: These findings provide robust evidence that greater alcohol intake, even within relatively moderate ranges, increases the risk of cancers of the aerodigestive tract, breast, colorectal and pancreatic cancer, and probably decreases the risk of thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma. Associations of alcohol intake with cancer risk were not modified by MHT use, adiposity or smoking, except in the case of upper aero-digestive cancers, where the alcohol-associated risk was largely confined to smokers.

Depression, anxiety, psychotropic drugs, and acute myocardial infarction: large prospective study of United Kingdom women.

BACKGROUND: Reported associations between depression and myocardial infarction in some studies might be explained by use of psychotropic drugs, residual confounding, and/or reverse causation (whereby heart disease precedes depression). We investigated these hypotheses in a large prospective study of UK women with no previous vascular disease. METHODS: At baseline in median year 2001 (IQR 2001-2003), Million Women Study participants reported whether or not they were currently being treated for depression or anxiety, their self-rated health, and medication use during the previous 4 weeks. Follow-up was through linkage to national hospital admission and mortality databases. Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the first myocardial infarction event in those reporting treatment for depression or anxiety (subdivided by whether or not the treatment was with psychotropic drugs) v. not, and stratified by self-reported health and length of follow-up. RESULTS: During mean follow-up of 13.9 years of 690 335 women (mean age 59.8 years) with no prior heart disease, stroke, transient ischaemic attack, or cancer, 12 819 had a first hospital admission or death from myocardial infarction. The aHRs for those reporting treatment for depression or anxiety with, and without, regular use of psychotropic drugs were 0.96 (95% CI 0.89-1.03) and 0.99 (0.89-1.11), respectively. No associations were found separately in women who reported being in good/excellent or poor/fair health or by length of follow-up. CONCLUSION: The null findings in this large prospective study are consistent with depression not being an independent risk factor for myocardial infarction.

Total sleep duration and daytime napping in relation to dementia detection risk: Results from the Million Women Study.

INTRODUCTION: There is inconsistent evidence on the associations of sleep duration and daytime napping with dementia risk. METHODS: In the Million Women Study, a total of 830,716 women (mean age, 60 years) were asked about sleep duration (<7, 7-8, >8 hours) and daytime napping (rarely/never, sometimes, usually) in median year 2001, and were followed for the first hospital record with any mention of dementia. Cox regression estimated dementia detection risk ratios (RRs) during 17-year follow-up in 5-year intervals. RESULTS: With 34,576 dementia cases, there was strong attenuation over follow-up in the RRs related to long sleep duration (>8 vs 7-8 hours) and usually napping (vs rarely/never). Short sleep duration was modestly, positively associated with dementia in the long term (RR = 1.08, 95% confidence interval [CI] 1.04-1.12). DISCUSSION: There was little evidence to suggest that long sleep duration and regular napping are associated with long-term dementia risk. Short sleep duration was modestly associated with dementia risk, but residual confounding cannot be excluded. HIGHLIGHTS: Long sleep duration was not associated with long-term dementia risk. Daytime napping was not associated with long-term dementia risk. There is some evidence for a small higher risk of dementia related to short sleep.

Body size in early life and the risk of postmenopausal breast cancer.

BACKGROUND: Greater early life adiposity has been reported to reduce postmenopausal breast cancer risk but it is unclear whether this association varies by tumour characteristics. We aimed to assess associations of early life body size with postmenopausal breast cancer and its subtypes, allowing for body size at other ages. METHODS: A total of 342,079 postmenopausal UK women who reported their body size at age 10, clothes size at age 20, and body mass index (BMI) at baseline (around age 60) were followed by record linkage to national databases for cancers and deaths. Cox regression yielded adjusted relative risks (RRs) of breast cancer, overall and by tumour subtype, in relation to body size at different ages. RESULTS: During an average follow-up of 14 years, 15,506 breast cancers were diagnosed. After adjustment for 15 potential confounders, greater BMI at age 60 was associated with an increased risk of postmenopausal breast cancer (RR per 5 kg/m2=1.20, 95%CI 1.18-1.22) whereas greater adiposity in childhood and, to a lesser extent, early adulthood, was associated with a reduced risk (0.70, 0.66-0.74, and 0.92, 0.89-0.96, respectively). Additional adjustment for midlife BMI strengthened associations with BMI at both age 10 (0.63, 0.60-0.68) and at age 20 (0.78, 0.75-0.81). The association with midlife adiposity was confined to hormone sensitive subtypes but early life adiposity had a similar impact on the risk of all subtypes. CONCLUSION: Early life and midlife adiposity have opposite effects on postmenopausal breast cancer risk and the biological mechanisms underlying these associations are likely to differ.

Alcohol intake and Parkinson's disease risk in the million women study.

BACKGROUND: Alcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive. OBJECTIVE: To determine the association between alcohol intake and PD risk in the Million Women Study, a large, prospective study of women in the UK. METHODS: Between 1996 and 2001, approximately 1.3 million women in the UK, mean age 56 (standard deviation, 5) years, were recruited into the Million Women Study. Information on alcohol intake, lifestyle factors, and medical history was collected at recruitment by questionnaire. Information on incident cases of PD was ascertained by record linkage to national hospital admission records and death registrations. We estimated multivariable-adjusted relative risks and corresponding 95% confidence intervals using Cox proportional hazards models according to categories of alcohol intake. RESULTS: During an average of 17.9 years of follow-up, 11,009 women had a new record of PD among 1,309,267 women. In drinkers, the multivariable-adjusted relative risk comparing women who drank more than 14 drinks of alcohol per week with women who drank 1 to 2 drinks of alcohol per week was 0.99 (95% confidence interval: 0.90, 1.10). Results did not materially change after excluding the first 10 years of follow-up (relative riskadjusted = 1.01; 95% confidence interval: 0.90, 1.13). There were no significant trends in alcohol-related PD risk among never smokers. Additionally, examining this association by type of alcohol intake also yielded null findings. CONCLUSION: These results do not support an association between alcohol intake and PD risk in women. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Coffee and pancreatic cancer risk among never-smokers in the UK prospective Million Women Study.

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 minimize these problems, but thus far such studies have included relatively small numbers of cases. In our 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 nondrinkers 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 vs. zero cups of coffee per day).

Screen-detected and interval colorectal cancers in England: Associations with lifestyle and other factors in women in a large UK prospective cohort.

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.

Body mass index in midlife and risk of attempted suicide and suicide: prospective study of 1 million UK women.

BACKGROUND: High body mass index (BMI) has been associated with lower risks of suicidal behaviour and being underweight with increased risks. However, evidence is inconsistent and sparse, particularly for women. We aim to study this relationship in a large cohort of UK women. METHODS: In total 1.2 million women, mean age 56 (s.d. 5) years, without prior suicide attempts or other major illness, recruited in 1996-2001 were followed by record linkage to national hospital admission and death databases. Cox regression yielded relative risks (RRs) and 95% confidence intervals (CIs) for attempted suicide and suicide by BMI, adjusted for baseline lifestyle factors and self-reported treatment for depression or anxiety. RESULTS: After 16 (s.d. 3) years of follow-up, 4930 women attempted suicide and 642 died by suicide. The small proportion (4%) with BMI <20 kg/m2 were at clearly greater risk of attempted suicide (RR = 1.38, 95% CI 1.23-1.56) and suicide (RR = 2.10, 1.59-2.78) than women of BMI 20-24.9 kg/m2; p < 0.0001 for both comparisons. Small body size at 10 and 20 years old was also associated with increased risks. Half the cohort had BMIs >25 kg/m2 and, while risks were somewhat lower than for BMI 20-24.9 kg/m2 (attempted suicide RR = 0.91, 0.86-0.96; p = 0.001; suicide RR = 0.79, 0.67-0.93; p = 0.006), the reductions in risk were not strongly related to level of BMI. CONCLUSIONS: Being underweight is associated with a definite increase in the risk of suicidal behaviour, particularly death by suicide. Residual confounding cannot be excluded for the small and inconsistent decreased risk of suicidal behaviour associated with being overweight or obese.

Adult cancer risk in women who were breastfed as infants: large UK prospective study.

There are known short-term benefits in breastfed infants versus bottle-fed infants in terms of lower risks of infection and obesity in infancy and childhood, but the long-term effect on the risk of adult cancers is unclear. In a cohort of 1 in 4 UK women born in 1935-1950 we report the incidence of adult cancers in relation to having been breastfed in infancy. In median year 2001 (interquartile range 2000-2003) 548,741 women without prior cancer reported whether they had been breastfed. There was 81% agreement between women's report of having been breastfed and information on breastfeeding recorded when they were 2 years old. Participants were followed by record-linkage to national cancer registration, hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CI) by having been breastfed or not for eight cancer sites with > 2000 incident cases and for related conditions, where appropriate. Of the eight cancers examined here one association was highly statistically significant: an increase in colorectal cancer incidence among women who had been breastfed versus not (RR 1.18, 95% CI 1.12-1.24, n = 8651). To investigate further the findings for colorectal cancer, we studied eight other gastro-intestinal conditions, and found increased risks in women who had been breastfed versus not for benign colorectal polyps (RR 1.09, 95% CI 1.05-1.13, n = 17,677) and for appendicitis (RR 1.19, 95% CI 1.07-1.31, n = 2108). The greater risks of adult colorectal cancer, colorectal polyps and appendicitis associated with having been breastfed in infancy suggest possible long-term effects of infant feeding practices on the gastrointestinal tract. Further studies are required to clarify this novel association.

Does happiness itself directly affect mortality? The prospective UK Million Women Study.

BACKGROUND: Poor health can cause unhappiness and poor health increases mortality. Previous reports of reduced mortality associated with happiness could be due to the increased mortality of people who are unhappy because of their poor health. Also, unhappiness might be associated with lifestyle factors that can affect mortality. We aimed to establish whether, after allowing for the poor health and lifestyle of people who are unhappy, any robust evidence remains that happiness or related subjective measures of wellbeing directly reduce mortality. METHODS: The Million Women Study is a prospective study of UK women recruited between 1996 and 2001 and followed electronically for cause-specific mortality. 3 years after recruitment, the baseline questionnaire for the present report asked women to self-rate their health, happiness, stress, feelings of control, and whether they felt relaxed. The main analyses were of mortality before Jan 1, 2012, from all causes, from ischaemic heart disease, and from cancer in women who did not have heart disease, stroke, chronic obstructive lung disease, or cancer at the time they answered this baseline questionnaire. We used Cox regression, adjusted for baseline self-rated health and lifestyle factors, to calculate mortality rate ratios (RRs) comparing mortality in women who reported being unhappy (ie, happy sometimes, rarely, or never) with those who reported being happy most of the time. FINDINGS: Of 719,671 women in the main analyses (median age 59 years [IQR 55-63]), 39% (282,619) reported being happy most of the time, 44% (315,874) usually happy, and 17% (121,178) unhappy. During 10 years (SD 2) follow-up, 4% (31,531) of participants died. Self-rated poor health at baseline was strongly associated with unhappiness. But after adjustment for self-rated health, treatment for hypertension, diabetes, asthma, arthritis, depression, or anxiety, and several sociodemographic and lifestyle factors (including smoking, deprivation, and body-mass index), unhappiness was not associated with mortality from all causes (adjusted RR for unhappy vs happy most of the time 0·98, 95% CI 0·94-1·01), from ischaemic heart disease (0·97, 0·87-1·10), or from cancer (0·98, 0·93-1·02). Findings were similarly null for related measures such as stress or lack of control. INTERPRETATION: In middle-aged women, poor health can cause unhappiness. After allowing for this association and adjusting for potential confounders, happiness and related measures of wellbeing do not appear to have any direct effect on mortality. FUNDING: UK Medical Research Council, Cancer Research UK.

The role of health-related behavioural factors in accounting for inequalities in coronary heart disease risk by education and area deprivation: prospective study of 1.2 million UK women.

BACKGROUND: Some recent research has suggested that health-related behaviours, such as smoking, might explain much of the socio-economic inequalities in coronary heart disease (CHD) risk. In a large prospective study of UK women, we investigated the associations between education and area deprivation and CHD risk and assessed the contributions of smoking, alcohol consumption, physical activity and body mass index (BMI) to these inequalities. METHODS: After excluding women with heart disease, stroke or cancer at recruitment, 1,202,983 women aged 56 years (SD 5 years) on average, were followed for first coronary event (hospital admission or death) and for CHD mortality. Relative risks of CHD were estimated by Cox regression, and the extent to which any association could be accounted for by smoking, alcohol, physical inactivity, and BMI was assessed by calculating the percentage reduction in the relevant likelihood-ratio (LR) statistic after adjustment for these factors, separately and together. RESULTS: A total of 71,897 women had a first CHD event (hospital admission or death) and 6032 died from CHD during 12 years follow-up. In analyses adjusted by age, birth cohort and region of residence only, lower levels of education and greater deprivation were associated with higher risks of CHD (P heterogeneity < 0.0001 for each); associations for education were found within every level of deprivation and for deprivation were found within every level of education. Smoking, alcohol consumption, physical inactivity and BMI accounted for most of the associations (adjustment for all four factors together reduced the LR statistics for education and for deprivation by 76 % and 71 %, respectively, for first CHD event; and by 87 % and 79 %, respectively, for CHD mortality). Of these four factors, adjustment for smoking resulted in the largest reduction in the LR statistic. Given the large reduction in the predictive values of education and deprivation after adjustment for only four health-related behavioural factors recorded just at recruitment, residual confounding might plausibly account for the remaining associations. CONCLUSIONS: Most of the association between CHD risk and education and area deprivation in UK women is accounted for by health-related behaviours, particularly by smoking and to a lesser extent by alcohol consumption, physical inactivity and BMI.

Risk Factors for Cataracts Treated Surgically in Postmenopausal Women.

PURPOSE: To identify risk factors for cataracts treated surgically in postmenopausal women. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: A total of 1 312 051 postmenopausal women in the UK Million Women Study, aged 56 years on average (standard deviation [SD], 4.8), without previous cataract surgery, hospital admission with cataracts, or cancer at baseline, were followed for cataracts treated surgically. METHODS: Cox regression was used to calculate adjusted relative risks (RRs) for cataract surgery by lifestyle factors, treatment for diabetes, reproductive history, and use of hormonal therapies. MAIN OUTCOME MEASURES: Cataract surgery identified by linkage to central National Health Service (NHS) records for inpatient and day-patient admissions (Hospital Episode Statistics for England and Scottish Morbidity Records in Scotland). RESULTS: Overall, 89 343 women underwent cataract surgery during an average of 11 (SD, 3) years of follow-up. Women with diabetes were at greatest risk (diabetes vs. no diabetes RR, 2.90; 95% confidence interval [CI], 2.82-2.97). Other factors associated with an increased risk of cataract surgery were current smoking (current smokers of ≥15 cigarettes/day vs. never smokers RR, 1.26; 95% CI, 1.23-1.30) and obesity (body mass index [BMI] ≥30 vs. <25 kg/m(2); RR, 1.12; 95% CI, 1.10-1.14). CONCLUSIONS: Diabetes, smoking, and obesity were risk factors for cataract surgery. Alcohol use, physical activity, reproductive history, and use of hormonal therapies had little, if any, association with cataract surgery risk.

Marital status and ischemic heart disease incidence and mortality in women: a large prospective study.

BACKGROUND: Being married has been associated with a lower mortality from ischemic heart disease (IHD) in men, but there is less evidence of an association for women, and it is unclear whether the associations with being married are similar for incident and for fatal IHD. We examined the relation between marital status and IHD incidence and mortality in the Million Women Study. METHODS: A total of 734,626 women (mean age 60 years) without previous heart disease, stroke or cancer, were followed prospectively for hospital admissions and deaths. Adjusted relative risks (RRs) for IHD were calculated using Cox regression in women who were married or living with a partner versus women who were not. The role of 14 socio-economic, lifestyle and other potential confounding factors was investigated. RESULTS: 81% of women reported being married or living with a partner and they were less likely to live in deprived areas, to smoke or be physically inactive, but had a higher alcohol intake than women who were not married or living with a partner. During 8.8 years of follow-up, 30,747 women had a first IHD event (hospital admission or death) and 2,148 died from IHD. Women who were married or living with a partner had a similar risk of a first IHD event as women who were not (RR = 0.99, 95% confidence interval (CI) 0.96 to 1.02), but a significantly lower risk of IHD mortality (RR = 0.72, 95% CI 0.66 to 0.80, P <0.0001). This lower risk of IHD death was evident both in women with and without a prior IHD hospital admission (respectively: RR = 0.72, 95% CI 0.60 to 0.85, P <0.0001, n = 683; and 0.70, 95% CI 0.62 to 0.78, P <0.0001, n = 1,465). These findings did not vary appreciably between women of different socio-economic groups or by lifestyle and other factors. CONCLUSIONS: After adjustment for socioeconomic, lifestyle and other factors, women who were married or living with a partner had a similar risk of developing IHD but a substantially lower IHD mortality compared to women who were not married or living with a partner.

Physical and mental health of 40,000 older women in England during the COVID-19 pandemic (2020-2021).

BACKGROUND: To assess factors associated with perceived changes in physical and mental health and with delays in seeking healthcare during the second and third COVID-19 lockdowns in England (2020-2021). METHODS: An online survey of Million Women Study participants collected data on 44,523 women, mean age 76 (SD = 4), October 2020-May 2021. These data were linked to data collected prospectively on Million Women Study participants at recruitment in median year 1998 and at re-surveys in 2011-2013, as well as to hospital admission data from 2017-2019. RESULTS: Of 40,821 participants with complete data on the outcomes of interest, 28% reported worse physical health and 26% worse mental health. After adjustment for age, region, education and survey period, poor/fair self-rated health (adjusted OR 2.71, 95% CI 2.52-2.91), having been told to shield (1.92, 1.79-2.05), obesity (2.17, 2.04-2.31) and other measures of poor health prior to the outbreak were all strongly related to worse physical health, as was being an informal carer (1.47, 1.38-1.56) and having a COVID-19 infection (1.64, 1.53-1.77). Depression (2.31, 2.06-2.58), poor/fair self-rated health (1.98, 1.84-2.13) and being an informal carer (1.69, 95% CI 1.58-1.80) were the factors most strongly related to worse mental health. Having poor/fair self-rated health (2.22, 2.05-2.40), obesity (1.58, 1.47-1.70) and being an informal carer (1.45, 1.34-1.56) were all strongly related to delaying seeking medical care. These associations remained essentially unchanged after exclusion of participants who had a COVID-19 infection. CONCLUSIONS: In a large sample of older women in England, just over a quarter reported a deterioration in their physical and mental health during the national lockdowns. In addition to the expected effect of a COVID-19 infection on physical health, the groups who were most likely to report such a deterioration were those with pre-existing morbidity and those who were caring for others as informal carers.

Rheumatoid arthritis and cancer risk in the Million Women Study.

BACKGROUND: Most previous studies of rheumatoid arthritis (RA) and cancer risk have lacked information on potential confounding factors. We investigated RA-associated cancer risks in a large cohort of women in the UK, taking account of shared risk factors. METHODS: In 1996-2001, women aged 50-64, who were invited for routine breast screening at 66 National Health Service (NHS) screening centres in England and Scotland, were also invited to take part in the Million Women Study. Participants provided information on sociodemographic, lifestyle and health-related factors, including RA, and were followed up for cancers and deaths. Cox regression yielded RA-associated hazard ratios (HRs) of 20 cancers, adjusted for 10 characteristics including smoking status and adiposity. RESULTS: Around 1.3 million women (half of those invited) were recruited into the study. In minimally adjusted analyses, RA was associated with the risk of 13 of the 20 cancers. After additional adjustment for lifestyle factors, many of these associations were attenuated but there remained robust evidence of RA-associated increases in the risk of lung (HR 1.21, 95% confidence interval 1.15-1.26), lymphoid (1.25, 1.18-1.33), myeloid (1.12, 1.01-1.25), cervical (1.39, 1.11-1.75) and oropharyngeal (1.40, 1.21-1.61) cancers, and decreases in the risk of endometrial (0.84, 0.77-0.91) and colorectal (0.82, 0.77-0.87) cancers. CONCLUSIONS: After taking account of shared risk factors, RA is positively associated with lung and certain blood and infection-related cancers, and inversely associated with colorectal cancer. These findings are consistent with existing hypotheses around immune response, susceptibility to infections, and chronic inflammation. The inverse association observed for endometrial cancer merits further investigation.

Exposure to aircraft and road traffic noise and associations with heart disease and stroke in six European countries: a cross-sectional study.

BACKGROUND: Although a number of studies have found an association between aircraft noise and hypertension, there is a lack of evidence on associations with other cardiovascular disease. For road traffic noise, more studies are available but the extent of possible confounding by air pollution has not been established. METHODS: This study used data from the Hypertension and Environmental Noise near Airports (HYENA) study. Cross-sectional associations between self-reported 'heart disease and stroke' and aircraft noise and road traffic noise were examined using data collected between 2004 and 2006 on 4712 participants (276 cases), who lived near airports in six European countries (UK, Germany, Netherlands, Sweden, Greece, Italy). Data were available to assess potential confounding by NO2 air pollution in a subsample of three countries (UK, Netherlands, Sweden). RESULTS: An association between night-time average aircraft noise and 'heart disease and stroke' was found after adjustment for socio-demographic confounders for participants who had lived in the same place for ≥ 20 years (odds ratio (OR): 1.25 (95% confidence interval (CI) 1.03, 1.51) per 10 dB (A)); this association was robust to adjustment for exposure to air pollution in the subsample. 24 hour average road traffic noise exposure was associated with 'heart disease and stroke' (OR: 1.19 (95% CI 1.00, 1.41), but adjustment for air pollution in the subsample suggested this may have been due to confounding by air pollution. Statistical assessment (correlations and variance inflation factor) suggested only modest collinearity between noise and NO2 exposures. CONCLUSIONS: Exposure to aircraft noise over many years may increase risks of heart disease and stroke, although more studies are needed to establish how much the risks associated with road traffic noise may be explained by air pollution.

Adiposity and risk of oesophageal cancer subtypes in the Million Women Study.

BACKGROUND: The strong association of body mass index (BMI) with increased oesophageal adenocarcinoma risk is established, but its relationship with oesophageal squamous cell carcinoma is less clear. There is little evidence regarding the association of abdominal adiposity with either subtype. METHODS: In a large prospective cohort of women in the UK, mean age 56.2 [standard deviation (SD) = 4.9] years, we investigated the risk of oesophageal adenocarcinoma and squamous cell carcinoma in relation to self-reported BMI, waist circumference (WC) and waist-hip ratio (WHR), using Cox regression to estimate adjusted relative risks (RR) and 95% confidence intervals (CIs), taking account of potential reverse causation bias. RESULTS: During mean follow-up of 17.7 (SD = 4.9) years, 1386 adenocarcinomas and 1799 squamous cell carcinomas of the oesophagus were registered among 1 255 529 women. Compared with women of BMI 22.5 to <25 kg/m2, those with BMI ≥35 kg/m2 had a 2.5-fold risk of adenocarcinoma (adjusted RR = 2.46, 95% CI = 1.99-3.05) and an almost 70% reduction in risk of squamous cell carcinoma (RR = 0.32, 95% CI = 0.22-0.46). These associations were broadly similar in each 5-year follow-up period, and were evident in both never and ever smokers, although somewhat stronger for squamous cell carcinoma among current and past smokers than in never smokers (Pheterogeneity = 0.007). After controlling for BMI, WC and WHR were associated with risk of squamous cell carcinoma but not adenocarcinoma. CONCLUSIONS: In this population of middle-aged women, there was robust evidence that greater BMI is associated with an increased risk of oesophageal adenocarcinoma and a reduced risk of squamous cell carcinoma.

Multimorbidity of cardiovascular disease subtypes in a prospective cohort of 1.2 million UK women.

OBJECTIVE: Cardiovascular multimorbidity (CVM) is the co-occurrence of multiple cardiovascular disease subtypes (CVDs) in one person. Because common patterns and incidence of CVM are not well-described, particularly in women, we conducted a descriptive study of CVM in the Million Women Study, a large population-based cohort of women. METHODS: UK women aged 50-64 years were followed up using hospital admissions and mortality records for an average of 19 years. CVM was defined as having ≥2 of 19 selected CVDs. The age-specific cumulative incidence of CVM between age 60 and 80 years was estimated. The numbers and proportions of individual, pairs and other combinations of CVDs that comprised incident CVM were calculated. For each individual CVD subtype, age-standardised proportions of the counts of other co-occurring CVDs were estimated. RESULTS: The age-specific likelihood of having CVM nearly doubled every 5 years between age 60 and 80 years. Among 1.2 million women without CVD at study baseline, 16% (n=196 651) had incident CVM by the end of follow-up. Around half of all women with CVM had a diagnosis of ischaemic heart disease (n=102 536) or atrial fibrillation (n=96 022), almost a third had heart failure (n=72 186) and a fifth had stroke (n=40 442). The pair of CVDs with the highest age-adjusted incidence was ischaemic heart disease and atrial fibrillation (18.95 per 10 000 person-years). Over 60% of individuals with any given CVD subtype also had other CVDs, after age standardisation. CONCLUSIONS: CVM is common. The majority of women with any specific CVD subtype eventually develop at least one other. Clinical and public health guidelines for CVD management should acknowledge this high likelihood of CVM.