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 58515 women with invasive breast cancer and 95067 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 greater than or equal to 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. (C) 2002 Cancer Research UK.

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.

al. Body measurements, estrogen availability and the risk of human breast cancer: a casecontrol study. Int J Cancer 1992;51:14-9. (4) Helzlsouer KJ, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW. Prospective study of serum micronutrients and ovarian cancer. J Natl Cancer Inst 1996;88:32-7. (5) Mettlin CJ, Piver MS. A case-control study of milk-drinking and ovarian cancer risk. Am J Epidemiol 1990;132:871-6. (6) Engle A, Muscat JE, Harris RE. Nutritional risk factors and ovarian cancer. Nutr Cancer 1991;15:239-47. (7) Risch HA, Jain M, Marrett LD, Howe GR. Dietary fat intake and risk of epithelial ovarian cancer. J Natl Cancer Inst 1994;86:140915. (8) Slattery ML, Schuman KL, West DW, French TK, Robison LM. Nutrient intake and ovarian cancer. Am J Epidemiol 1989;130:497502. (9) Polychronopoulou A, Tzonou A, Hsieh CC, Kaprinis G, Rebelakos A, Toupadaki N, et al. Reproductive variables, tobacco, ethanol, coffee and somatometry as risk factors for ovarian cancer. Int J Cancer 1993;55:402-7. (10) Moller H, Mellemgaard A, Lindvig K, Olsen JH. Obesity and cancer risk: a Danish recordlinkage study. Eur J Cancer 1994;30A:344-50. (11) Thurnham DI, Davies JA, Crump BJ, Situnayake RD, Davis M. The use of different lipids to express serum tocopherol: lipid ratios for the measurement of vitamin E status. Ann Clin Biochem 1986;23(Pt 5):514-20. (12) Salkeld RM, Keller HE. Roche guidelines for vitamin status in adults. Basel, Switzerland: Vitamins and Fine Chemicals Division, Hoffmann-La Roche, 1988. (13) Gerber M, Astre C, Segala C, Saintot M, Scali J, Simony-Lafontaine J, et al. Oxidantantioxidant status alterations in cancer patients: relationship to tumor progression. J Nutr 1996;126(4 Suppl):1201S-7S. (14) Saintot M, Astre C, Pujol H, Gerber M. Tumor progression and oxidant-antioxidant status. Carcinogenesis 1996;7:1267-71. (15) Das NP, Ma CW, Salmon YM. The relationship of vitamin A, cholesterol, and triglycerides to the incidence of ovarian cancer. Biochem Med Metab Biol 1987;37:213-9.

and smoking (o = -0.26,P = 0.01).These results confirm that, in nutritional manage- ment of gestational diabetes, carbohydrate intake has to be higher than 200 g/day and that fat intake must be restricted.Growth and nutrition of children of Maghrebian origin living in Paris area.

A significant change of vitamin E and malondialdehyde plasma concentrations was reported in breast cancer patients. This change was unexpected because vitamin E was higher and malondialdehyde lower in cases than in controls, and the difference was more significant in young rather than older women. The first aim of this study was to determine whether these changes were associated only with breast cancer, or with hormone-related cancers, and/or cancers associated with nutritional risk factors or with all types of cancers. Measurements were performed before therapy on 269 hospital-based controls and on 146 patients with various carcinomas. Vitamin E:total cholesterol increased and malondialdehyde plasma concentration decreased with tumor size and progression, without relation to the site. The second aim was to understand the difference in the change observed between young and old breast cancer patients. These analytes were measured in 365 breast cancer patients according to three prognosis factors: pathology, tumor size and estrogen receptors. Vitamin E:total cholesterol significantly decreased with estrogen receptor amount. Malondialdehyde plasma concentration decreased with severity of pathology and tumor size. Together, these data support the association of an altered oxidant-antioxidant profile in cancer patients with tumor growth and progression.

BACKGROUND The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. METHODS Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. FINDINGS The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95 percent CI] in current users 1.24 [1.15-1.33], 2p<0.00001; 1-4 years after stopping 1.16 [1.08-1.23], 2p=0.00001; 5-9 years after stopping 1.07 [1.02-1.13], 2p=0.009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1.01 [0.96-1.05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0.88 (0.81-0.95; 2p=0.002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90 percent of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0.5 (95 percent CI 0.3-0.7), 1.5 (0.7-2.3), and 4.7 (2.7-6.7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons...

It has been hypothesized that beta-carotene mediates the association between low serum cholesterol levels and increased risk of lung cancer. It follows from this assumption that this association should be greater in population strata with a low intake of beta-carotene than in with those with a high intake. To investigate this hypothesis, we analysed dietary beta-carotene, plasma beta-carotene and serum cholesterol levels in 20 male smokers with lung cancer and 103 male smoking controls, a subsample taken from a larger case-control study on oxidant-antioxidant status. As predicted, we found that the association between low serum cholesterol levels and lung cancer risk was greater in subjects with low plasma beta-carotene. Controlling for plasma beta-carotene decreased but did not negate the magnitude of the inverse association between serum cholesterol and lung cancer. A low serum cholesterol level tended to increase the risk associated with low plasma beta-carotene. Our data suggest that a low plasma beta-carotene does not totally explain the association between serum cholesterol and lung cancer.

Groupe d'Epidemiologie Metabolique, Institut National de la Sante et de la Recherche Medicale-CRLC, 34094 Montpellier Cedex 5. France

The relationship between aging and cancer is complex because the intrication takes place at the cell, the organism and the environment levels. On the other hand, carcinogenesis is a multi-step process, and different mechanisms may be involved in each step. For example, oxidants and antioxidants may play a different role depending upon the phase considered. Tumors in older patients are generally described as slow growing. The difference in tumor aggressiveness between young and older patients is especially obvious in breast cancer patients. The age specificity of some breast risk factors suggests that breast cancer which has been diagnosed in an aged woman was induced late in her life. We address the question whether the characteristics of a senescent organism with regards to oxidant-antioxidant status could be causally related to the slow evolution of tumors in old patients.

A hospital-based case-control study was conducted over 4 years in Southern France to assess the pattern of established risk factors for breast cancer and to examine its variation according to age at diagnosis. Cases studied (450) were women admitted to the Montpellier Cancer Institute, with histologically confirmed primary breast carcinoma. Controls (576) were patients from a nearby hospital admitted in the early stages of a neurological or mild psychological diseases and from a clinic for general surgery. Any patient with malignant tumours, chronic and cardiovascular diseases were excluded. The total population globally showed the commonly reported pattern for these risk factors. When stratified by age, the reproductive factors occurring early in life (menarche, first full term pregnancy) were shown to be significant risk factors only in the youngest group of patients and do not seem to influence risk in older women, for whom risk factors are those occurring later in life (menopause, obesity). This suggests a complex involvement of the reproductive and sociodemographic features with the various stages of the 'natural history' of breast cancer.