Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58 515 women with invasive breast cancer and 95 067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19–1.45, P<0.00001) for an intake of 35–44 g per day alcohol, and 1.46 (1.33–1.61, P<0.00001) for ⩾45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5–8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98–1.07, and for current smokers=0.99, 0.92–1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver

Predicting post-absorptive protein and amino acid metabolism

ABSTRACT Sustainable production of adequate quantities of food to support a growing human population is a worldwide goal. Under current feeding conditions in the United States, dairy cattle convert dietary nitrogen to milk nitrogen with 25% efficiency. The remaining 75% is excreted, which contributes to air and water quality problems and reduces economic performance of the industry. Efficiency could be improved to 29% if protein was given to just meet current NRC requirements. Additional improvements may be achievable, but only with improved knowledge of amino acid (AA) requirements. The current metabolizable protein requirement model overestimates true requirements due to lack of knowledge of AA supply and requirements and to intrinsic limitations in system data and assumptions. Existing protein supply models based on passage and degradation rates are biased, which undermines predictions of AA supply. The use of an equation driven solely by protein solubility of each ingredient in the diet with no consideration of the effects of passage rate yielded unbiased predictions with significant improvements in precision. However, this still leaves a problem in predicting the AA composition of the ruminally undegraded protein (RUP). Current models generally assume that RUP AA composition equals the parent ingredient composition, but assessments of RUP AA composition indicate that this is false. Thus, bias is being introduced into predictions of the absorbed AA supply, which hampers derivation of estimates of AA digestion and absorption from the small intestine. Emerging isotope-based methods hold promise in allowing assessment of AA availability from individual ingredients in vivo, which will allow construction of a database of true ingredient AA bioavailabilities. These efforts will eventually allow development of more robust predictions of AA supply. On the AA requirement side, numerous data indicate that the efficiency of metabolizable protein use for lactation is variable and maximally 45%, whereas most models assume an efficiency of 65% or greater. The efficiencies of individual AA are centered on the protein efficiency value with those lower in efficiency, likely being provided in large excess. A better representation of the use efficiency of individual AA would allow improvements in overall animal N efficiency. Variable efficiency is driven by regulatory mechanisms that control protein synthesis in response to the supply of energy and individual AA and circulating concentrations of hormones and these drivers act independently and additively. Under this theory, protein synthesis can respond to nutrients other than the one identified as most limiting. Reflecting this regulation in our requirement models will allow better prediction of AA efficiency and enable construction of diets that minimize excess of individual AA by optimizing the energy and hormonal signals to improve N efficiency. Models of such an interacting system have been developed and shown to be superior in performance to models based on current paradigms

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver

Multinational comparative clinical trial of long-acting injectable contraceptives: norethisterone enanthate given in two dosage regimens and depot-medroxyprogesterone acetate. A preliminary report

A multicentre phase III clinical trial has been undertaken to compare norethisterone enantate (NET-EN) given by two different treatment regimens and depot-medroxyprogesterone acetate (DMPA). After 18 months of observation, preliminary findings are reported for 1,589 women who received DMPA 150mg every 90 days; 790 women who received NET-EN 200mg every 60 days; and 796 women who received NET-EN, 200mg every 60 days for 6 months, then 200mg every 84 days. The overall discontinuation rates per 100 women were similar for all three treatment groups over the 18 months observation (61.8-63.5 per 100 women). The discontinuation rates for bleeding problems and for personal reasons were also similar for all three treatment groups. However, terminations due to amenorrhoea were significantly higher among DMPA users (12.1 and 17.4 per 100 women at 12 and 18 months) as compared with both NET-EN groups (6.8-8.2 per 100 women at 12 months and 10.4-10.9 per 100 women at 18 months). The only significan

PID associated with fertility regulating agents. Task Force on Intrauterine Devices, Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization.

A WHO sponsored matched case-control study to examine the association between acute pelvic inflammatory disease (PID) and contraceptive use was conducted in 8 developing country and 4 developed country centres. 608 cases of acute febrile non-postpartum PID were individually matched with 1216 controls; 437 of the cases came from centres in developing countries and 171 from developed country centres. Among parous women the relative risks of a first episode of PID associated with current IUD use were 2.3 in developing and 4.1 in developed country centres. Nulliparous women in developed countries had a relative risk of 11.5, but the risks could not be estimated for nulliparous developing country women because there were insufficient IUD users. The high risk among nulliparous women was in part due to bias arising from probable differences in sexual activity in unmarried cases and controls. The risks for parous women aged 15-24 were 9.1 in developed and 2.9 in developing country centres. The risks of PID associated with current IUD use were much higher in women with a past history of PID. An increased PID risk was also found with past IUD use. Use of oral contraceptives or conventional contraceptives was associated with a reduced risk of first episode PID in parous but not in nulliparous women. Irrespective of contraceptive use, a past history of PID increased the risk of recurrent infection, and abortion was associated with an increased risk of first episode and recurrent PID. In conclusion, except for women under 25, the present study showed similar risks of PID related to contraceptive use, past infection or abortion in parous women from developed and developing country centres