Disability and participation in breast and bowel cancer screening in England: a large prospective study.

BACKGROUND: There is limited information about participation in organised population-wide screening programmes by people with disabilities. METHODS: Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants. RESULTS: Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62-0.65) and in bowel cancer screening (RR=0.75, 0.73-0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation. CONCLUSION: Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability.

Cancer risk among 21st century blood transfusion recipients.

Background: Some carcinogenic viruses are known to be transmissible by blood transfusion. Intensive viral screening of transfused blood now exists in most countries. In the UK, high-sensitivity nucleic acid amplification tests for hepatitis C virus were introduced in 1999 and it was thought that this would reduce, and possibly eliminate, transfusion-related liver cancer. We aimed to investigate cancer risk in recipients of blood transfusion in 2000 or after. Methods: A total of 1.3 million UK women recruited in 1998 on average were followed for hospital records of blood transfusion and for cancer registrations. After excluding women with cancer or precancerous conditions before or at the time of transfusion, Cox regression yielded adjusted relative risks of 11 site-specific cancers for women with compared to without prior blood transfusion. Results: During follow up, 11 274 (0.9%) women had a first recorded transfusion in 2000 or after, and 1648 (14.6%) of them were subsequently diagnosed with cancer, a mean 6.8 years after the transfusion. In the first 5 years after transfusion there were significant excesses for most site-specific cancers examined, presumably because some had preclinical cancer. However, 5 or more years (mean 8 years) after blood transfusion, there were significant excess risks only for liver cancer (adjusted relative risk = 2.63, 95%CI 1.45-4.78) and for non-Hodgkin lymphoma (adjusted relative risk = 1.74, 1.21-2.51). When analyses were restricted to those undergoing hip or knee replacement surgery, the commonest procedure associated with transfusion, these relative risks were not materially altered. Conclusions: In a large cohort of UK women, transfusions in the 21st century were associated with long-term increased risks of liver cancer and non-Hodgkin lymphoma. Some of these malignancies may have been caused by carcinogenic agents that are not currently screened for in transfused blood.

Lifestyle and reproductive risk factors associated with anal cancer in women aged over 50 years.

BACKGROUND: Anal cancer incidence increases with age and is higher in women than men. Risk factors in this group other than high-risk human papillomavirus infection are unclear. METHODS: In all, 1.3 million women were recruited in 1996-2001 and followed for incident anal cancer. Cox regression models were used to calculate relative risks (RRs) for anal cancer by various potential risk factors. RESULTS: Five hundred and seventeen incident anal cancers were registered over 13 years of follow-up. The largest RR was associated with a history of cervical intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59-6.28). Other factors associated with significantly increased risks in multivariate analyses were: ever smoking (RR=1.49, 1.24-1.80); previous use of oral contraceptives (RR=1.51, 1.24-1.83); nulliparity (RR=1.61, 1.24-2.07); tubal ligation (RR=1.39, 1.13-1.70) and not living with a partner (RR=1.82, 1.40-2.38). The association with smoking was significantly greater for squamous cell carcinoma than adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04). CONCLUSIONS: History of CIN 3, smoking, past oral contraceptive use, nulliparity, tubal ligation and not living with a partner are risk factors for anal cancer in women. There was a significant increase in risk associated with smoking for squamous cell anal cancers but not adenocarcinomas.

Nationwide bowel cancer screening programme in England: cohort study of lifestyle factors affecting participation and outcomes in women.

BACKGROUND: In 2006, the National Health Service Bowel Cancer Screening Programme in England (NHSBCSP) began offering routine population-based biennial faecal occult blood testing (FOBt) at ages 60-69. There is, however, limited information on how characteristics of individuals affect participation and outcomes of screening, and we studied this association by linking NHSBCSP data to a large prospective cohort of women. METHODS: Electronic linkage of the NHSBCSP and Million Women Study records identified 899 166 women in the study cohort with at least one invitation for screening. NHSBCSP provided information on screening acceptance, FOBt results, screen-detected colorectal cancer and other outcomes. The Million Women Study provided prospectively collected information on personal and lifestyle factors. Multiple regression was used to estimate relative risks (RRs) of factors associated with acceptance and outcomes of screening. RESULTS: Overall, 70% of women (628 976/899 166) accepted their first invitation for bowel cancer screening, of whom 9133 (1.5%) were FOBt-positive, 743 (0.1%) had screen-detected colorectal cancer and 3056 (0.5%) had screen-detected colorectal adenoma. Acceptance was lower in women from the most than the least deprived tertile, in South Asians and in Blacks than in Whites, in current than in never smokers and in obese than in normal weight women: adjusted RRs (95% confidence interval) for acceptance vs not, 0.90 (0.90-0.90); 0.77 (0.75-79); 0.94 (0.92-0.96); 0.78 (0.77-0.78); and 0.88 (0.88-0.89), respectively: P<0.001 for each. These factors were also associated with an increased risk of being FOBt-positive and of having screen-detected adenoma, but were not strongly associated with the risk of screen-detected colorectal cancer. Relative risks for screen-detected adenoma were 1.22 (1.12-1.34), 2.46 (1.75-3.45), 1.61 (1.05-2.48), 1.53 (1.38-1.68) and 1.77 (1.60-1.95), respectively (P<0.001 for all, except for Blacks vs Whites P=0.03). Use of hormone therapy for menopause was associated with reduced risk of screen-detected adenoma, RR ever vs never use, 0.87 (0.81-0.93), P<0.001 and colorectal cancer, 0.78 (0.68-0.91), P=0.001. INTERPRETATION: Among women in England, socioeconomic and lifestyle factors strongly affect participation in routine bowel cancer screening, risk of being FOBt-positive and risk of having screen-detected colorectal adenoma. However, screen-detected colorectal cancer risk is not strongly related to these factors.

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.

BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK.

Birth weight and adult cancer incidence: large prospective study and meta-analysis.

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.

Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom.

BACKGROUND: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. METHODS: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. 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 vs never=1.03, 95% confidence interval (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 associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65-0.96). CONCLUSIONS: 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.

Incidence of thyroid cancer in England by ethnic group, 2001-2007.

BACKGROUND: Thyroid cancer incidence is increasing worldwide, but with large variations in incidence that may reflect either diagnostic bias or true ethnic differences. We sought to determine the effect of ethnicity on the incidence of thyroid cancer in England, a multiethnic population with a single health-care system. METHODS: We analysed 11,263 thyroid cancer registrations with ethnicity obtained by linkage to the Hospital Episodes Statistics database. Incidence rate ratios (RRs) adjusted for age, sex and income were calculated for the six main non-White ethnic groups in England compared with Whites and to each other. RESULTS: Thyroid cancer incidence was higher in all ethnic groups, except Indians, compared with Whites: in Pakistanis (RR 1.79, 99% floating confidence interval (FCI) 1.47-2.19); Bangladeshis (RR 1.99, 99% FCI 1.46-2.71); Black Africans (RR 1.69, 99% FCI 1.34-2.13); Black Caribbeans (RR 1.56, 99% FCI 1.25-1.93); and Chinese (RR 2.14, 99% FCI 1.63-2.80). CONCLUSION: The risk of thyroid cancer in England varies significantly by ethnicity. The elevated incidence in most ethnic minorities is unlikely to be due to diagnostic bias and warrants further investigation.

Ethnic differences in breast cancer incidence in England are due to differences in known risk factors for the disease: prospective study.

BACKGROUND: In the United Kingdom, breast cancer incidence is lower in South Asian and Black women than in White women, but the extent to which this is due to known risk factors is unknown. In a large prospective study, we describe breast cancer incidence by ethnicity, before and after adjustment for known risk factors for the disease. METHODS: Women were recruited into the Million Women Study in 1996-2001, when information on reproductive and lifestyle factors known to influence the risk of breast cancer was obtained. Ethnicity was determined from study questionnaires and hospital admission data. Cox regression models were used to calculate adjusted relative risks (RR) for incident breast cancer in South Asians and Blacks compared with Whites. RESULTS: Analyses included 5877 South Asian, 4919 Black, and 1,038,144 White women in England. The prevalence of 8 out of the 9 risk factors for breast cancer examined, differed substantially by ethnicity (P<0.001 for each), such that South Asian and Black women were at a lower risk of the disease than White women. During 12.2 years of follow-up incident breast cancer occurred in 217 South Asians, 180 Blacks, and 45,191 Whites. As expected, breast cancer incidence was lower in South Asians (RR=0.82, 95% CI 0.72-0.94) and Blacks (RR=0.85, 0.73-0.98) than in Whites when the analyses were adjusted only for age and region of residence. However, after additional adjustment for the known risk factors for the disease, breast cancer incidence was similar to that of Whites, both in South Asians (0.95, 0.83-1.09) and in Blacks (0.91, 0.78-1.05). CONCLUSION: South Asian and Black women in England have lower incidence rates of breast cancer than White women, but this is largely, if not wholly, because of differences in known risk factors for the disease.

Body size in relation to incidence of subtypes of haematological malignancy in the prospective Million Women Study.

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.

Persistent effects of women's parity and breastfeeding patterns on their body mass index: results from the Million Women Study.

OBJECTIVE: To explore the long-term effects of women's childbearing patterns on their body mass index. DESIGN: Cross-sectional analysis. SETTING: Population-based study of UK women. PARTICIPANTS: 740 628 postmenopausal participants in the Million Women Study who reported their height, weight, reproductive histories and other relevant factors. MAIN OUTCOME MEASURES: Standardized mean BMI (kg m(-2)) in groups defined by their parity and breastfeeding history. RESULTS: Women were aged 57.5 (s.d. 4) years on average, and had a mean BMI of 26.2 kg m(-2) (s.d. 5); 88% were parous, with 2.1 (s.d. 1.2) children on average. The standardised mean BMI increased progressively with the number of births from 25.6 kg m(-2) (95% confidence interval (CI): 25.5-25.6) in nulliparous women up to 27.2 kg m(-2) (CI: 27.2-27.3) for women with four or more births, a difference of 1.7 kg m(-2) (CI: 1.6-1.7). Among the parous women 70% had ever breastfed and their average total duration of breastfeeding was 7.7 (s.d. 8.8) months. At every parity level the standardised mean BMI was significantly lower among women who had breastfed than those who had not, decreasing by 0.22 kg m(-2) (CI: 0.21-0.22) for every 6 months of breastfeeding, that is, women's mean BMI was 1% lower for every 6 months that they had breastfed. These associations were highly statistically significant (P<0.0001) and independent of the effects of socioeconomic group, region of residence, smoking and physical activity. CONCLUSIONS: Childbearing patterns have a persistent effect on adiposity in this population. The reduction in BMI associated with just 6 months breastfeeding in UK women could importantly reduce their risk of obesity-related disease as they age.

Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study.

BACKGROUND: Current use of menopausal hormone therapy (HT) increases the risk of venous thromboembolism (VTE) and the formulations used may affect risk. METHODS: A total of 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During 3.3 million years of follow-up, 2200 women had an incident VTE, diagnosed, on average, 1.5 years after last reporting HT use. RRs in current vs. never users at last reporting varied by HT formulation: the risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR = 2.07 [95%CI, 1.86-2.31] vs. 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, the risk from HT varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] vs. 1.91 [1.69-2.17]; Pheterogeneity = 0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first 2 years after starting HT than later (Pheterogeneity = 0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate. CONCLUSIONS: The risk of VTE varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate.

Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study.

BACKGROUND: Previous research suggests associations of lower alcohol intake and higher tobacco consumption with increased risks of haematological malignancy. The prospective Million Women Study provides sufficient power for reliable estimates of subtype-specific associations in women. METHODS: Approximately 1.3 million middle-aged women were recruited in the United Kingdom during 1996-2001 and followed for death, emigration and cancer registration until 2009 (mean 10.3 years per woman); potential risk factors were assessed by questionnaire. Adjusted relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162 incident cases of haematological malignancy were recorded, including 7047 lymphoid and 2072 myeloid cancers. Among predominantly moderate alcohol drinkers, higher intake was associated with lower risk of lymphoid malignancies, in particular diffuse large B-cell lymphoma (relative risk 0.85 per 10 g alcohol per day (95% confidence interval 0.75-0.96)), follicular lymphoma (0.86 (0.76-0.98)) and plasma cell neoplasms (0.86 (0.77-0.96)). Among never- and current smokers, higher cigarette consumption was associated with increased risk of Hodgkin lymphoma (1.45 per 10 cigarettes per day (1.22-1.72)), mature T-cell malignancies (1.38 (1.10-1.73)) and myeloproliferative/myelodysplastic disease (1.42 (1.31-1.55)). CONCLUSION: These findings confirm and extend existing evidence for associations of subtypes of haematological malignancy with two common exposures in women.

Ovarian cancer and smoking: individual participant meta-analysis including 28,114 women with ovarian cancer from 51 epidemiological studies.

BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. METHODS: Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28,114 women with and 94,942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. FINDINGS: After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1·06, 95% CI 1·01-1·11, p=0·01). Of 17,641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0·0001). For mucinous cancers, incidence was increased in current versus never smokers (1·79, 95% CI 1·60-2·00, p<0·0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2·25, 95% CI 1·91-2·65 vs 1·49, 1·28-1·73; p(heterogeneity)=0·01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0·81, 95% CI 0·72-0·92, p=0·001) and clear-cell ovarian cancer risks (0·80, 95% CI 0·65-0·97, p=0·03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0·99, 95% CI 0·93-1·06, p=0·8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. INTERPRETATION: The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis. FUNDING: Cancer Research UK and MRC.

A short-term increase in cancer risk associated with daytime napping is likely to reflect pre-clinical disease: prospective cohort study.

BACKGROUND: Sleep disturbance, a correlate of which is daytime napping, has been hypothesised to be associated with risk of breast and other cancers. METHODS: We estimated relative risks (RR) of breast and other invasive cancers by the reported frequency of daytime napping in a large prospective cohort of middle-aged women in the UK. RESULTS: During an average of 7.4 years of follow-up, 20 058 breast cancers and 31 856 other cancers were diagnosed. Over the first 4 years of follow-up, daytime napping (sometimes/usually vs rarely/never) was associated with slightly increased risks of breast cancer (RR=1.10, 95% CI 1.06-1.15) and of other cancers (RR=1.12, 1.08-1.15), but the RRs decreased significantly with increasing follow-up time (P=0.001 and P=0.01, respectively, for trend). Four or more years after baseline, there was no elevated risk of breast cancer (RR=1.00, 0.96-1.05), and only marginally greater risk of other cancers (RR=1.04, 1.01-1.07). CONCLUSION: The effect of pre-clinical disease is a likely explanation for the short-term increased risk of breast and other cancers associated with daytime napping.

Postmenopausal endometrial cancer risk and body size in early life and middle age: prospective cohort study.

BACKGROUND: Greater adiposity in early life has been linked to increased endometrial cancer risk in later life, but the extent to which this association is mediated through adiposity in later life is unclear. METHODS: Among postmenopausal women who had never used menopausal hormone therapies and reported not having had a hysterectomy, adjusted relative risks (RRs) of endometrial cancer were estimated using Cox regression. RESULTS: Among 249 791 postmenopausal women with 7.3 years of follow-up on average (1.8 million person-years), endometrial cancer risk (n=1410 cases) was strongly associated with current body mass index (BMI) at baseline (RR=1.87 per 5 kg m(-2) increase in BMI, 95% confidence interval (CI): 1.77-1.96). Compared with women thinner than average at age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09-1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77-1.06). Similarly, compared with women with clothes size 12 or less at age 20, the increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61-2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88-1.22). CONCLUSION: Among women who have never used hormone therapy for menopause, the association between body size in early life and endometrial cancer risk in postmenopausal women can be largely explained by women's current BMI.

Reproductive factors and risk of oesophageal and gastric cancer in the Million Women Study cohort.

BACKGROUND: Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study. METHODS: Among 1,319,409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years' observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre- or peri-menopausal women (RRs 1.46, 1.07-2.00 and 1.59, 1.15-2.20, respectively; P≤0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause (RR, 95% CI per 5 years younger at menopause 1.18, 1.05-1.34 for oesophageal cancer and 1.18, 1.04-1.34 for stomach cancer, P(trend)=0.01 for both). For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women (RR 1.31, 1.11-1.55; P=0.002). When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited. CONCLUSION: Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing.

Fluid intake and incidence of renal cell carcinoma in UK women.

BACKGROUND: It has been suggested that the apparent protective effect of alcohol intake on renal cell carcinoma may be due to the diluting effect of carcinogens by a high total fluid intake. We assessed the association between intakes of total fluids and of specific beverages on the risk of renal cell carcinoma in a large prospective cohort of UK women. METHODS: Information on beverage consumption was obtained from a questionnaire sent ∼3 years after recruitment into the Million Women Study. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for renal cell carcinoma associated with beverage consumption adjusted for age, region of residence, socioeconomic status, smoking, and body mass index. RESULTS: After an average of 5.2 years of follow-up, 588 cases of renal cell carcinoma were identified among 779,369 women. While alcohol intake was associated with a reduced risk of renal cell carcinoma (RR for ≥ 2 vs <1 drink per day: 0.76; 95% CI: 0.61-0.96; P for trend=0.02), there was no association with total fluid intake (RR for ≥ 12 vs <7 drinks per day: 1.15; 95% CI: 0.91-1.45; P for trend=0.3) or with intakes of specific beverages. CONCLUSIONS: The apparent protective effect of alcohol on the risk of renal cell carcinoma is unlikely to be related to a high fluid intake.