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.

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.

Histological subtypes of ovarian cancer associated with parity and breastfeeding in the prospective Million Women Study.

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 < 0.001) and weak, if any, effect for endometrioid, high-grade serous, or mucinous tumours. We found little association with age at first or last birth. There was about a 10% risk reduction per 12-months breastfeeding (RR = 0.89, 0.84-0.94, p < 0.001), with no significant heterogeneity by histotype, but statistical power was limited. In this large prospective study, ovarian cancer risk associated with parity varied substantially by tumour histotype. Nulliparity was associated with a substantially greater overall risk than expected from the effect of a single birth, especially for clear cell and endometrioid tumours, perhaps suggesting that infertility is associated with these histotypes.

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.

Ovarian cancer survival by stage, histotype, and pre-diagnostic lifestyle factors, in the prospective UK Million Women Study.

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.

Alcohol drinking patterns and liver cirrhosis risk: analysis of the prospective UK Million Women Study.

BACKGROUND: Alcohol is a known cause of cirrhosis, but it is unclear if the associated risk varies by whether alcohol is drunk with meals, or by the frequency or type of alcohol consumed. Here we aim to investigate the associations between alcohol consumption with meals, daily frequency of consumption, and liver cirrhosis. METHODS: The Million Women Study is a prospective study that includes one in every four UK women born between 1935 and 1950, recruited between 1996 and 2001. In 2001 (IQR 2000-03), the participants reported their alcohol intake, whether consumption was usually with meals, and number of days per week it was consumed. Cox regression analysis yielded adjusted relative risks (RRs) for incident cirrhosis, identified by follow-up through electronic linkage to routinely collected national hospital admission, and death databases. FINDINGS: During a mean of 15 years (SD 3) of follow-up of 401 806 women with a mean age of 60 years (SD 5), without previous cirrhosis or hepatitis, and who reported drinking at least one alcoholic drink per week, 1560 had a hospital admission with cirrhosis (n=1518) or died from the disease (n=42). Cirrhosis incidence increased with amount of alcohol consumed (≥15 drinks [mean 220 g of alcohol] vs one to two drinks [mean 30 g of alcohol] per week; RR 3·43, 95% CI 2·87-4·10; p<0·0001). About half of the participants (203 564 of 401 806) reported usually drinking with meals and, after adjusting for amount consumed, cirrhosis incidence was lower for usually drinking with meals than not (RR 0·69, 0·62-0·77; p<0·0001; wine-only drinkers RR 0·69, 0·56-0·85; all other drinkers RR 0·72, 0·63-0·82). Among 175 618 women who consumed seven or more drinks per week, cirrhosis incidence was greater for daily consumption than non-daily consumption (adjusted RR 1·61, 1·40-1·85; p<0·0001). Daily consumption, together with not drinking with meals, was associated with more than a doubling of cirrhosis incidence (adjusted RR 2·47, 1·96-3·11; p<0·0001). INTERPRETATION: In middle-aged women, cirrhosis incidence increases with total alcohol intake, even at moderate levels of consumption. For a given weekly intake of alcohol, this excess incidence of cirrhosis is higher if consumption is usually without meals, or with daily drinking. FUNDING: UK Medical Research Council and Cancer Research UK.

The effect of caffeine consumption and nausea on the risk of miscarriage.

Evidence for a harmful effect of caffeine intake on risk of miscarriage (spontaneous abortion) is inconsistent and nausea during pregnancy has been claimed to explain any association seen. The objective of this analysis was to determine whether caffeine consumption both before and during pregnancy influenced the risk of miscarriage in a group of pregnant women in the UK. We examined the association with maternal caffeine intake in a case-control study of 474 nulliparous women. Participants were recruited during the years 1987-89 from the Royal Berkshire Hospital in Reading and from a large group practice situated within the hospital's catchment area. Cases were 160 women with a clinically diagnosed miscarriage and controls were 314 pregnant women attending for antenatal care. Information on coffee/tea/cola consumption and potential confounders was collected by interview and caffeine content was assigned to individual drinks according to published data on caffeine content of beverages. Compared with a maternal caffeine intake of < 151 mg/day, we found evidence that caffeine consumption > 300 mg/day doubled the risk of miscarriage. Adjusted odds ratios were 1.94 [95% CI 1.04, 3.63] for 301-500 mg/day and 2.18 [95% CI 1.08, 4.40] for > 500 mg/day. This effect could not be explained by nausea in pregnancy. Nausea appeared to be strongly independently associated with a reduced risk of miscarriage (test for trend P < 0.0001). There was no evidence that prepregnancy caffeine consumption affected the risk. Our results indicate that high caffeine consumption during pregnancy (>300 mg/day), in particular coffee consumption, is an independent risk factor for increased risk and nausea is an independent protective factor for a lower risk of miscarriage.