Dietary fat, calories, and the risk of breast cancer in postmenopausal women: a prospective population-based study

We tested the hypothesis that a high-fat diet increases the risk of breast cancer in a population-based study of 590 women aged 40-79 years who were without known breast cancer when they provided a quantitative 24-hour diet recall. Fifteen postmenopausal women were diagnosed with incident breast cancer during the next 15 years (approximately 7600 person-years of follow-up). These women had significantly higher age-adjusted intake of all fats (monounsaturated, polyunsaturated, and saturated), and oleic, linoleic, and linolenic acids, with a stepwise increase in risk across tertiles of intake. Fat intake was associated with total calories, protein, and carbohydrates, and women with incident breast cancer consumed more calories, protein, and carbohydrates than did other subjects. When each nutrient variable (calories, fats, protein, and carbohydrates) was adjusted for age, body mass index, age at menopause, parity, and alcohol consumption, the strongest risks for incident breast cancer were associated with total calories (relative risk per standard deviation = 2.72, 95% confidence interval = 1.51-4.89, p = 0.002) and total fats (relative risk per standard deviation = 2.01, 95% confidence interval = 1.19-3.41, p = 0.01). Fat composition of the diet, expressed either as percent of energy or as fat intake adjusted for calories by regression analysis, was not significantly associated with risk of breast cancer. These results support the hypothesis that total calorie consumption, as well as dietary fat consumption, is a risk factor for breast cancer in postmenopausal women, and parallel observations in animal models.     

Meat, fat and risk of breast cancer: a case-control study from Uruguay

To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.     

A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer

Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environment interaction with red meat intake among participants in the prospective Physicians' Health Study. Baseline blood samples from 212 men subsequently diagnosed with colorectal cancer during 13 years of follow-up were genotyped, along with 221 controls. NAT genotypes were analyzed by a PCR-restriction fragment length polymorphism method. Effect modification of the relation of red meat intake and risk of colorectal cancer by NAT genotype was assessed using conditional logistic regression. There was no overall independent association of NAT acetylation genotypes and colorectal cancer risk. The relative risks for the rapid acetylation genotype were 0.93 [95% confidence interval (CI), 0.61-1.42] for NAT1, 0.80 (95% CI, 0.53-1.19) for NAT2, and 0.81 (95% CI, 0.52-1.27) for NAT1/NAT2 combined. We observed a stronger association of red meat intake with cancer risk among NAT rapid acetylators, especially among men 60 years old or older. Among those men who were rapid acetylators for both NAT1 and NAT2, consumption of >1 serving of red meat per day was associated with a relative risk of 5.82 (95% CI, 1.11-30.6) compared with consumption of < or = 0.5 serving per day (P, trend = 0.02). These prospective data, which need to be confirmed in other studies, suggest that polymorphisms in the NAT genes confer differential susceptibility to the effect of red meat consumption on colorectal cancer risk.     

Occupation and breast cancer mortality in a prospective cohort of US women

We report the isolation of the functional form of the Ca-ATPase from porcine cardiac sarcoplasmic reticulum (SR) membranes, taking advantage of the ability of this enzyme to bind to the nucleotide site affinity dye, Reactive Red 120. Conditions that optimize the solubility and functional stability of the cardiac Ca-ATPase in detergent during the purification procedure are essential to its recovery. The purified Ca-ATPase migrates as a single band on Coomassie blue-stained polyacrylamide gels and exhibits high specific activity (2.5 IU at 25 degreesC) and functional stability. Similar enrichment of the Ca-ATPase estimated from either relative amounts of the 100-kDa protein band on polyacrylamide gels or steady-state concentrations of phosphorylated enzyme intermediate (E-P) demonstrate that neither nonfunctional Ca-ATPases nor non-Ca-ATPase proteins migrating with an apparent molecular weight of 100 kDa constitute a significant fraction of these preparations. Steady-state levels of E-P are 1.3 and 8.6 nmol/mg protein, respectively, for native cardiac SR membranes and the final purified fraction. These values, in comparison to the maximum value (9.1 nmol/mg) for the 110-kDa protein, agree well with estimates of total Ca-ATPase abundance from gel densitometry for both preparations and indicate full site reactivity, i.e., one phosphorylation site for each 110-kDa cardiac Ca-ATPase polypeptide chain.     

Dietary fat intake and risk of lung cancer: a prospective study of 51,452 Norwegian men and women

The relationship between incidence of lung cancer and intake of dietary fats, high-fat foods, fish, and fish products was studied in 25,956 men and 25,496 women aged 16-56 years attending Norwegian health screening between 1977 and 1983. Linkage to the Cancer Registry of Norway and the Central Bureau of Statistics of Norway ensured a complete follow-up until 31 December 1991. Diet was recorded on a semiquantitative food-frequency questionnaire, and 153 cases of lung cancer were identified during follow-up. Mean age at diagnosis was 56 years. After adjusting for smoking status, gender, age at screening, and attained age, significant lower risks were found for cod liver oil supplement (incidence rate ratio (IRR) = 0.5, 95% CI = 0.3-1.0) and for skim milk compared to whole milk (IRR = 0.5, 95% CI = 0.3-0.9)). No association was found with dietary cholesterol and saturated fat. A threshold of increased risk starting at the second quartile was seen for mono- and polyunsaturated fat. The potential protective effect of cod liver oil, a supplement rich in preformed vitamin A, omega-3 fatty acids, and monounsaturated fat, has to our knowledge, not been reported before. Confounding from lifestyle is possible, but the result deserves further investigation.     

Diet and breast cancer risk in a cohort of Finnish women

The associations between dietary antioxidant vitamins, dietary fiber, and selected foods and risk of breast cancer were studied in 4697 initially cancer-free women, aged 15 years or older. At baseline (1967-1972) the women were interviewed for total habitual diet over the preceding year. During a 25-year follow-up period 88 breast cancer cases were diagnosed. There was a significant inverse gradient between milk consumption and occurrence of breast cancer, whereas higher consumption of fried meat was associated with increased risk of breast cancer. No significant relationships were found between the intakes of vitamin E, vitamin C, beta-carotene, lycopene, lutein or dietary fiber and the occurrence of breast cancer.     

Well-done meat intake and the risk of breast cancer

BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.     

Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women

A positive association between postmenopausal serum levels of total estradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Before 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted of ER-positive, ER-negative, and ER-unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percentage of free estradiol were greater (21-28% and 6-7%, respectively) in cases than in controls. Conversely, the mean percentage of estradiol bound to SHBG was 9-12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER-positive, ER-negative, and ER-unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER-positive to ER negative tumors than with the hypothesis that ER status identifies two distinct types of breast cancer.     

Testicular cancer risk and maternal parity: a population-based cohort study

The aim was to study, in a population-based cohort design, whether first-born sons run a higher risk of testicular cancer than later born sons; to investigate whether this difference in risk was affected by birth cohort, age of the son, maternal age, interval to previous delivery and other reproductive factors; and, finally, to evaluate to what extent changes in women's parity over time might explain the increasing incidence of testicular cancer. By using data from the Civil Registration System, a database was established of all women born in Denmark since 1935 and all their children alive in 1968 or born later. Sons with testicular cancer were identified in the Danish Cancer Registry. Among 1015994 sons followed for 15981 967 person-years, 626 developed testicular cancer (443 non-seminomas, 183 seminomas). Later born sons had a decreased risk of testicular cancer (RR = 0.80, 95% CI = 0.67-0.95) compared with first-born sons. The RR was 0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for seminomas. There was no association between testicular cancer risk and overall parity of the mother, maternal or paternal age at the birth of the son, or maternal age at first birth. The decreased risk of testicular cancer among later born sons was not modified by age, birth cohort, interval to the previous birth, sex of the first-born child, or maternal age at birth of the son or at first birth. The increased proportion of first-borns from birth cohort 1946 to birth cohort 1969 only explained around 3% of an approximated two-fold increase in incidence between the cohorts. Our data document a distinctly higher risk of testicular cancer in first-born compared with later born sons and suggest that the most likely explanation should be sought among exposures in utero. The increase in the proportion of first-borns in the population has only contributed marginally to the increase in testicular cancer incidence.     

Risk for endometrial cancer following breast cancer: a prospective study in Sweden

Many marine organisms are luminescent. The proteins that produce the light include a primary light producer (aequorin or luciferase) and often a secondary photoprotein that red shifts the light for better penetration in the ocean. Green fluorescent protein is one such secondary protein. It is remarkable in that it autocatalyzes the formation of its own fluorophore and thus can be expressed in a variety of organisms in its fluorescent form. The recent determination of its 3D structure and other physical characterizations are revealing its molecular mechanism of action.     

A prospective study of plasma prolactin levels and subsequent risk of breast cancer

Plasma prolactin was measured in 2,572 pre-menopausal, 628 menopausal, and 1,666 peri- and post-menopausal women who were apparently healthy. Breast cancer was subsequently diagnosed in 47 of these women at a median time of 5 years after blood collection (pre-cancer cases). Prolactin levels in pre-menopausal cases increased significantly with age whereas this was not found in matched controls. The perimenopausal cases were characterized by extreme variability in prolactin levels. In post-menopausal women who developed breast cancer, the prolactin levels were significantly elevated, being at or above the 70th percentile for the controls. In this group the results are consistent with prolactin acting as a late-stage tumour promoter.     

Coping with a breast cancer diagnosis: A prospective study.

Employing the stress and coping theory of R. S. Lazarus and S. Folkman (1984), this study followed 117 women age 40+ regarding personality, cognitive appraisal, coping, and mood variables before breast biopsy, after diagnosis, and, for those who had cancer, after surgery. Upon biopsy, 36 received a cancer diagnosis, and 81 received a benign diagnosis. The 2 groups did not differ on appraisals, coping, or affect before diagnosis. With prebiopsy affect controlled, cancer patients reported more negative affect postbiopsy than did benign patients. Postsurgery, cancer patients expressed less vigor and more fatigue than benign patients, but the groups did not differ on other negative emotions. Prebiopsy, psychosocial predictors accounted for 54% and 29% of the variance in negative and positive emotion, respectively. Prebiopsy variables also predicted postbiopsy and postsurgery mood; cognitive coping was a particularly important predictor of high distress and low vigor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low risk of perinatal transmission of human papillomavirus: results from a prospective cohort study

In an experimental infection model mimicking acute Actinobacillus pleuropneumoniae (Ap) infection in swine (Sus scrofa) by aerosol inoculation, the development of a number of typical clinical signs was accompanied by a prototypic acute phase reaction encompassing fever and an acute phase protein response peaking at around 2 days after infection. Haptoglobin, C-reactive protein (CRP), and major acute phase protein (MAP) responded with large increases in serum levels, preceding the development of specific antibodies by 4-5 days. Serum amyloid A protein (SAA) was also strongly induced. The increase, kinetics of induction and normalization were different between these proteins. It is concluded that experimental Ap-infection by the aerosol route induces a typical acute phase reaction in the pig, and that pig Hp, CRP, MAP, and SAA are major acute phase reactants. These findings indicate the possibility of using one or more of these reactants for the nonspecific surveillance of pig health status.     

Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study

OBJECTIVE: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses' Health Study. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. SUBJECTS: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. MAIN OUTCOME MEASURES: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. RESULTS: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking,use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. CONCLUSIONS: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.     

A meta-analysis of studies of dietary fat and breast cancer risk

One hundred and seventy cancerous lesions observed among 159 esophagectomised specimens were systematically investigated with histochemical staining methods in addition to the ordinary hematoxylin-eosin staining. About 2/3 of them, 113 lesions, were entirely consisted of the squamous elements, regardless with pearl-formation or not, Group 1. On the contrary, the remaining 57 lesions (33.5%) showed foci of esophageal gland-like transformation, Group 2. Those lesions were specified by constituent epithelia with esophageal glandular epithelia-like characteristics; positive for epithelial mucin, secretory component and S-100 protein. Such esophageal gland-like structures could be demonstrated exclusively in cancerous foci penetrated through the lamina muscularis mucosa. Those 113 lesions of the Group 1 did not show any such transformation even by the meticulous examination of the whole lesion by the step sectioning. Those lesions of the Group 2 had a distinct tendency of the perpendicular mural penetration and submucosal extension than the horizontal mucosal involvement, giving rise a characteristic appearance resembling to submucosal tumors. On the contrary, those of the Group 1 showed an ordinary mural extension pattern corresponding to the extent of mucosal involvement, so-to-speak, a typical features of common esophageal cancer. No outstanding difference in biological behaviours could be obviated between two groups so far examined; survival rate, lymph node metastasis, vascular permeation, intraepithelial extension, etc.     

Cancer risk among women with cosmetic breast implants: a population-based cohort study in Sweden

Complementary DNAs encoding the heavy and light chains of the Fab fragment of mouse agglutinating monoclonal antibody against human red blood cells were cloned by polymerase chain reaction and their nucleotide sequences were determined. The sequence analysis showed that the variable regions of the heavy and light chains were the members of mouse heavy-chain subgroup IIa and kappa light-chain subgroup I, respectively. A few unusual amino acids in the constant regions of the heavy chain were also recognized.     

Colorectal adenoma in patients with a history of breast cancer: a prospective study in Taiwan

The increased incidence of colorectal cancer in women with a history of breast cancer is well established. However, the relationship between the prevalence of adenomatous polyps and breast cancer is still controversial. We conducted a prospective study of the incidence of colorectal polyps in patients with a history of breast cancer in Taiwan. Eighty-nine patients (86 women and 3 men) received colonoscopy to test for precancerous lesions. Mean age was 49.4 +/- 10.4 years. Twelve polyps (9 adenomatous, 2 hyperplastic, 1 inflammatory) (13.5%) and one cancer (1.1%) were found. The mean age of patients with and without colorectal neoplasia was 56.3 +/- 9.4 and 48.2 +/- 10.2 years respectively, (p < 0.005); 10 out of 13 patients (77%) with colorectal neoplasia were over 50 (p < 0.1). Compared with a study of Chinese people in Hong Kong, our population had a lower incidence of colorectal adenomatous polyps, but breast cancer patients have a greater risk of developing colorectal cancer than the general population in Taiwan.     

Alcohol consumption and risk of breast cancer: a multicentre Italian case-control study

The relationship between alcohol consumption and breast cancer risk was investigated using data from a co-operative case-control study conducted in Italy between 1991 and 1994 on 2569 incident, histologically confirmed breast cancer cases and 2588 controls in hospital for acute, non-neoplastic, non-hormone related conditions. Overall, 915 (38%) cases and 1048 (43%) controls were abstainers. Compared with them, the odds ratio (OR), adjusted only for age, was 1.31 (95% confidence interval (CI) 1.13-1.53) for drinkers and became 1.39 (95% CI 1.(1)21-1.60) after correction for measurement error. The multivariate OR was 1.21 for drinkers of < or = 5.87 g/day and 1.23, 1.19, 1.21, 1.41 for drinkers of 5.88-13.40, 13.41-24.55, 24.56-27.60, > 27.60 g/day, respectively. The trend in risk was significant (chi 2 = 12.28, P < 0.0005). The association was apparently stronger in premenopausal women (OR = 1.80 for > 27.60 g/day). Considering the different types of alcoholic beverages (wine, beer, digestives, grappa and other spirits), a significant direct trend in breast cancer risk was seen for wine with an OR of 1.27 (95% CI 1.06-1.53) for the category > 26.34 g/day. The ORs were also above unity for beer, grappa, digestives and spirits drinkers. No appreciable interaction was observed between alcohol drinking and body mass index, smoking, or any other covariate considered. Thus, the present data, based on a validated alcohol consumption questionnaire and on a population characterised by a relatively high alcohol consumption in women, confirmed that alcohol drinking is moderately related to breast cancer risk. If causal, this association could explain 12% (95% CI, 5-19%) of breast cancers in Italy, thus representing one of the major avoidable risk factor for breast cancer.     

Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico

Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which DDT is still being used to control malaria. In a hospital-based case-control study, we compared 141 histologically confirmed cases of breast cancer with 141 age-matched controls (+/-3 years). All subjects were identified at three referral hospitals of Mexico City between March 1994 and April 1996. Reproductive histories and other variables were obtained by structured interviews, DDT/DDE levels were determined in serum by gas-liquid chromatography. The arithmetic mean of serum DDE in lipid basis was 562.48 +/- 676.18 ppb (range, 10.24-4661.44) for the cases and 505.46 +/- 567.22 ppb (range, 0.004 to 4361.75) for the controls, but this difference was not statistically significant. The age-adjusted odds ratios for breast cancer regarding the serum level of DDE were 0.69 (95% confidence interval, 0.38-1.24) and 0.97 (confidence interval, 0.55-1.70) for the contrasts between tertile 1 (lowest level) and tertiles 2 and 3, respectively. These estimates were unaffected by adjustment for body mass, accumulated time of breast-feeding and menopause, and other breast cancer risk factors. These results do not lend support to the hypothesis that DDT is causally related to breast cancer at the body-burden levels found in our study population but do not exclude the possibility that higher levels of exposure could still play a role in the etiology of this tumor.