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Premenopausal bilateral breast cancer is characterized by a strong family risk, and, consequently, a high probability that inherited susceptibility genes may be segregating in these families. Determining whether risk factors that affect other breast cancer cases have a similar effect in the etiology of bilateral breast cancer is of interest. Therefore, as part of an ongoing genetic-epidemiologic study of premenopausal bilateral breast cancer, we conducted a case-control analysis of reproductive variables, benign breast disease, alcohol, and smoking. Cases had premenopausal bilateral breast cancer, and their unaffected sisters served as controls. A set of reproductive variables--including earlier age at menarche, nulliparity, and late age at first full term pregnancy--appeared to increase the risk of breast cancer; the corresponding confidence limits, however, were wide and straddled the null. In addition, other variables associated with increased premenopausal bilateral breast cancer risk were: use of oral contraceptives, history of benign breast disease, and high alcohol consumption. We found no positive association for smoking. Nulliparity and late age at first full-term pregnancy appeared to have different effects in women with family histories of breast cancer than in women without such a history. We detected no substantial effect modification for the other risk factors. In general, risk factors previously identified for breast cancer (usually postmenopausal, unilateral cases) appear also to increase the risk for premenopausal, bilateral breast cancer.

Increased body mass index (BMI) has been found to be associated with elevated risk of postmenopausal breast cancer. Whether BMI is related to premenopausal breast cancer has not yet been established. We performed a meta-analyses of data from 23 studies that provided information on BMI and incidence of premenopausal breast cancer. Overall, the data support a modest inverse association. For a BMI difference of 8 kg per m2, that is, the difference between a thin person and someone who is morbidly obese, the random effects estimate of the rate ratio from the four cohort studies was 0.70 [95% confidence interval (CI) = 0.54-0.91], and the random effects estimate of the odds ratio from the 19 case-control studies was 0.88 (95% CI = 0.76-1.02). Because of substantial heterogeneity among the study-specific estimates, however, we also examined the influence of certain aspects of study design. Case-control studies with community controls had a more inverse association, whereas case-control studies that interviewed cases shortly after diagnosis applied the same exclusion criteria to cases and controls, or with confounder adjustment beyond age had a more positive association between BMI and breast cancer. Possible reasons for the discrepancies among the case-control studies are discussed.

Previous studies using current or recent adult body weight and body mass index are inconclusive as to a possible effect of increased body mass on premenopausal breast cancer incidence. Only five studies have presented data on early adult body mass, and no study has reported these data for premenopausal bilateral breast cancer. Because premenopausal bilateral breast cancer is assumed to be partly genetic and partly environmental in origin, it is crucial to identify possible modifiable risk factors for this cancer. We present data on early adult body weight and body mass (Quetelet Index, QI) from a case-control study of 142 premenopausal bilateral breast cancer cases from Los Angeles County, California, Connecticut, and Quebec, Canada, and 229 sister controls. The odds ratio (and 95% confidence interval) of premenopausal breast cancer adjusted for age, education, alcohol consumption, and oral contraceptive use was 0.7 (0.3-1.4) for women in the highest tertile of QI at age 18. The results do not suggest that elevated body mass index at a young age increases the risk of premenopausal bilateral breast cancer, but lend only weak support to the hypothesis of an inverse association between body mass index and premenopausal breast cancer.

The incidence of adenocarcinoma of the cervix in the USA more than doubled between the early 1970s and the mid 1980s among women under 35 years of age. It was suggested that this increase was due to the introduction of oral contraceptives in the early 1960s. Adenocarcinoma of the cervix diagnosed in women born after 1935 was identified between 1977 and 1991 from the Los Angeles County Cancer Surveillance Program. Data from personal interviews of 195 cases and 386 controls (matched on age, race, and neighbourhood) were analysed. Information on medical, sexual, contraceptive, and reproductive history, previous cervical smears, and sexually transmitted diseases was collected. Compared with never use, ever use of oral contraceptives was associated with twice as great a risk of adenocarcinoma of the cervix (adjusted odds ratio 2.1, 95% CI 1.1-3.8). The highest risk was observed for oral contraceptive use for more than 12 years (4.4, 1.8-10.8). No additional increased risk was found for early age at start of oral contraceptive use, use before age 20 or before first pregnancy, time since first use, time since last use, or particular formulations, once total duration of use had been accounted for.

Background: It has been known for some time that oral contraceptives substantially reduce the risk of endometrial and ovarian cancer, but they do not reduce the risk of breast cancer. A hormonal contraceptive regimen has been developed which uses a gonadotropin-releasing hormone against (GnRHA) to suppress ovarian function, and this regimen includes the administration of very low doses of both estrogen and progestogen. This hormonal contraceptive regimen attempts to minimize exposure of the breast epithelium to these steroids and to preserve the maximum beneficial effects of estrogen, while still preventing endometrial hyperplasia., Purpose: Our purpose was to determine whether changes occurred in mammographic densities between baseline and 1 year for women on this hormonal contraceptive regimen with reduced estrogen and progestogen levels compared with women in a control group., Methods: Twenty-one women were randomly assigned in a 2:1 ratio to the GnRHA-based contraceptive group (14 women) or to a control group (seven women). The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle. The control group received no medication. Baseline and 1-year follow-up mammograms of contraceptive and control subjects were reviewed in a blinded fashion by two radiologists., Results: Comparison of the changes between the baseline and 1-year mammograms in the two groups of women showed significant (P = .039) reduction in mammographic densities at 1 year for women on the contraceptive regimen. Assessing the reduction in mammographic densities by noting the fineness of fibrous septae showed a highly significant (P = .0048) difference in the contraceptive regimen group. One of the women on the contraceptive regimen was withdrawn from the study because of poor compliance., Conclusion: The reduced estrogen and progestogen exposures to the breast that were achieved by the hormonal contraceptive regimen resulted in substantial reductions in follow-up mammographic densities at 1 year compared with baseline. Although there is no direct evidence that such a reduction in densities will lead to a reduced risk of breast cancer, indirect evidence for a protective effect of this regimen is that early menopause reduces breast cancer risk, and that menopause is associated with a reduction in mammographic densities.

Objectives: This research used food frequency data to investigate dietary patterns associated with fat intake., Methods: Data from the 1987 National Health Interview Survey of 20,143 adults were used to determine correlations between fat (adjusted for kilocalories) and both nutrient and food group intakes. Median food and nutrient intakes were determined within quartiles of percentage of kilocalories from fat., Results: Intakes of vegetables, fruits, cereals, fish/chicken, low-fat milk, alcoholic beverages, vitamin C, percentage of kilocalories from carbohydrates, carotenoids, folate, dietary fiber, carbohydrates, and vitamin A decreased as percentage of kilocalories from fat increased. Intakes of salty snacks, peanuts, processed and red meats, whole milk and cheese, desserts, eggs, fried potatoes, table fats, cholesterol, vitamin E, sodium, protein, and energy increased with percentage of kilocalories from fat. Results by demographic subgroups showed few differences from those found in the total population., Conclusions: Fat intake is consistently associated with specific dietary patterns. Such patterns need to be evaluated concurrently in studies of diet and chronic disease.

There is a four to fivefold variation in breast cancer incidence rates across different countries. The lowest rates are observed in Asia, and the highest rates are observed in western Europe and North America. The incidence of breast cancer has increased in all countries since 1960. We studied in detail (whenever possible) the changes in incidence and mortality between 1955 and 1990 in four age groups (35-44, 45-54, 55-64 and 65-74) for 11 "representative" countries (USA, England and Wales, Norway, Hungary, Yugoslavia, Spain, Colombia, Singapore, Japan, India and China). The largest increase in incidence took place in Japan and Singapore. The incidence rate for women aged 35-44 in Japan doubled between 1960 and 1985 and by 1985 was roughly two thirds the USA rate. There has been essentially no change in mortality rates in the USA, England and Wales or Norway, whereas there has been a 50-60% increase in Japan, Singapore and Hungary. Most of the observed increase in incidence rates in the USA, England and Wales and Norway may be "artefactual", that is, due to changes in screening patterns. Screening may also have contributed to the rate increase in other countries, but outside western Europe and North America the major part of the increase is likely to be due to changes in known and suspected breast cancer risk factors.

To identify systematically the nutrient and food group intakes associated with a low-fat diet, the authors used the detailed dietary information collected from 10,306 individuals aged 32-86 years in the 1982-1984 National Health Epidemiologic Follow-up Study. Intakes of vitamin C and percentages of calories from carbohydrates, dietary fiber, poultry, low-fat dairy products, fruits, vegetables, cereals, and whole grains were markedly higher, while intakes of protein, total fat, saturated fat, oleic and linoleic acids, cholesterol, sodium, all red meats, high-fat dairy products, eggs, nuts, white bread, fried potatoes, desserts, fats, and oils were much lower in the quartile with the lowest percentage of calories from fat. These dietary patterns associated with a low-fat diet were essentially constant across strata of age, sex, race, and socioeconomic status. This study suggests that individuals on a low-fat diet substitute certain carbohydrate-rich foods such as fruits and vegetables for fat. Given these associations between low-fat diets and other dietary factors independently associated with certain cancers, these dietary factors should be considered potential confounders in studies of dietary fat and these cancers.

We estimated the effect of oral contraceptive (OC) use on premenopausal bilateral breast cancer in a matched case-control study. One hundred forty-four cases were identified from population-based registries of Los Angeles County, California, and of Connecticut and from the major hospitals in Montreal and Quebec City. Matched controls were the unaffected sisters of the cases. When age was included in the model, ever-use of OCs for 1 year or more was associated with an odds ratio 1.7 (95% confidence interval = 1.0-2.9). The odds ratios associated with 1-2, 3-6, and 7 years of use were 1.2 (0.61-2.4), 2.5 (1.2-5.3), and 2.0 (0.93-4.2), respectively. Too few women had used OCs before their first full-term pregnancy or before age 25 for these estimates to be informative. Restricting the analyses to women who had ever given birth yielded an odds ratio for ever-use of OCs of 2.1 (1.0-4.4). The results indicate an increased risk of premenopausal bilateral breast cancer associated with OC use.

Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables.

Relationships between milk intake and cancer incidence were investigated after 11 1/2 years of follow-up of 15,914 individuals. A diagnosis of cancer was made in a total of 1,422 individuals. No association was established with total cancer incidence, in analyses adjusted for sex, age and residential characteristics. However, a strong positive association with milk consumption was observed for cancers of the lymphatic organs (odds ratio 3.4 for greater than or equal to 2 glasses per day vs less than 1; 95% confidence interval 1.4-8.2). An inverse association was found for cancer of the bladder. Kidney cancer and cancers of the female reproductive organs (except the uterine cervix) showed weak positive associations with milk intake.

Relationships between reproductive factors and risk of cancer of the uterine corpus were investigated in a prospective study of 62,079 women in Norway. A total of 420 cases were diagnosed during follow-up, from 1961 through 1980. The risk of endometrial carcinoma decreased significantly with increasing parity as well as with increasing age at first and last birth. The estimated odds ratio for women with 5 or more births versus uniparous was 0.60 in analyses with adjustment for age and residence characteristics. For first birth at age greater than or equal to 35 versus less than or equal to 19 the odds ratio was 0.48, and for last birth at age greater than or equal to 40 versus less than or equal to 24 we found an odds ratio of 0.45, in analyses with additional adjustment for parity. Significant associations were also found with age at menarche and menopause, the highest risks being observed for women with early menarche or late menopause. The different reproductive variables seemed to affect the risk of sarcomas of the uterine corpus and the risk of endometrial carcinomas in a similar way.

Factorial analyses of subjectively felt health complaints in a population of 400 males and 74 females revealed nine orthogonal (independent) factors. One factor (Factor 4) involved pain in the neck, pain in the back, pain in arms and shoulders, and migraine. This type of complaint did not relate to anxiety and depression. The prevalence of muscle pains varied between the sexes, and the types of occupations. Shiftwork was also important. 54% of the women and 40% of the men in the total population had some forms of muscle pain, but only 8% of the women and 3% of the men felt this to be a really serious problem. Psychological factors explained only moderate amounts of variance of muscle pain when the population was taken as a whole. However, within each type of occupation, psychological factors explained a considerable amount of the variance.