Dietary fat intake and the risk of coronary heart disease in women

BACKGROUND: The relation between dietary intake of specific types of fat, particularly trans unsaturated fat and the risk of coronary disease remains unclear. We therefore studied this relation in women enrolled in the Nurses' Health Study. METHODS: We prospectively studied 80,082 women who were 34 to 59 years of age and had no known coronary disease, stroke, cancer, hypercholesterolemia, or diabetes in 1980. Information on diet was obtained at base line and updated during follow-up by means of validated questionnaires. During 14 years of follow-up, we documented 939 cases of nonfatal myocardial infarction or death from coronary heart disease. Mutivariate analyses included age, smoking status, total energy intake, dietary cholesterol intake, percentages of energy obtained from protein and specific types of fat, and other risk factors. RESULTS: Each increase of 5 percent of energy intake from saturated fat, as compared with equivalent energy intake from carbohydrates, was associated with a 17 percent increase in the risk of coronary disease (relative risk, 1.17; 95 percent confidence interval, 0.97 to 1.41; P=0.10). As compared with equivalent energy from carbohydrates, the relative risk for a 2 percent increment in energy intake from trans unsaturated fat was 1.93 (95 percent confidence interval, 1.43 to 2.61; P<0.001); that for a 5 percent increment in energy from monounsaturated fat was 0.81 (95 percent confidence interval, 0.65 to 1.00; P=0.05); and that for a 5 percent increment in energy from polyunsaturated fat was 0.62 (95 percent confidence interval, 0.46 to 0.85; P= 0.003). Total fat intake was not signficantly related to the risk of coronary disease (for a 5 percent increase in energy from fat, the relative risk was 1.02; 95 percent confidence interval, 0.97 to 1.07; P=0.55). We estimated that the replacement of 5 percent of energy from saturated fat with energy from unsaturated fats would reduce risk by 42 percent (95 percent confidence interval, 23 to 56; P<0.001) and that the replacement of 2 percent of energy from trans fat with energy from unhydrogenated, unsaturated fats would reduce risk by 53 percent (95 percent confidence interval, 34 to 67; P<.001). CONCLUSIONS: Our findings suggest that replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease in women than reducing overall fat intake.     

Serum antibodies against Helicobacter pylori proteins VacA and CagA are associated with increased risk for gastric adenocarcinoma

Infection with Helicobacter pylori is associated with the development of gastric cancer. To study whether the infection with H. pylori strains expressing the vacuolating cytotoxin (VacA) and/or the cytotoxin-associated protein (CagA) is associated with an increased risk of developing gastric adenocarcinoma, sera of 90 patients with gastric cancer and 90 matched controls with cardiovascular diseases were investigated for the presence of antibodies to VacA and CagA by immunoblot. Although no significant difference in the overall H. pylori seropositivity was found between cancer patients and controls, antibodies against VacA or CagA were significantly more frequent in cancer patients than in control subjects. Seventy-five (97.4%) of 77 H. pylori-positive patients in the cancer group, but only 60 (84.5%) of 71 H pylori-positive control patients had antibodies against either VacA or CagA (chi 2 = 6.63; relative risk, 2.00; 95% confidence interval, 1.18-3.39; P = 0.01). The presence of antibodies against VacA or CagA alone was also associated with an increased cancer risk (92.2% vs 80.3%; chi 2 = 5.30; relative risk, 1.74; 95% confidence interval, 1.08-2.78; P = 0.021, for VacA; and 87.0% vs 74.6%; chi 2 = 4.90; relative risk, 1.61; 95% confidence interval, 1.06-2.45; P = 0.037, for CagA). The relative risk for gastric cancer was mainly elevated in patients under 65 years, but not in patients at or over 65 years. There is evidence that infection with VacA- or CagA-producing H. pylori strains increases the risk of developing gastric cancer, especially in younger patients.     

Neuropathology in the neurosciences. A system in transition

BACKGROUND: Despite the use of warfarin, major systemic embolism remains an important complication in patients with heart-valve replacement. Although the addition of antiplatelet agents has the potential to reduce this complication, their efficacy and safety when given in combination with warfarin are uncertain. METHODS: In a randomized, double-blind, placebo-controlled trial, we assessed the efficacy and safety of adding aspirin (100 mg per day) to warfarin treatment (target international normalized ratio, 3.0 to 4.5) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism. RESULTS: A total of 186 patients were randomly assigned to aspirin and 184 to placebo, and they were followed for up to 4 years (average, 2.5). Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients (1.9 percent per year) and 24 placebo-treated patients (8.5 percent per year) (risk reduction with aspirin, 77 percent; 95 percent confidence interval, 44 to 91 percent; P < 0.001). Major systemic embolism, nonfatal intracranial hemorrhage, or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin (3.9 percent per year) and 28 patients assigned to placebo (9.9 percent per year) (risk reduction, 61 per cent; 95 percent confidence interval, 24 to 80 percent; P = 0.005); major systemic embolism or death from any cause occurred in 13 patients (4.2 percent) and 33 patients (11.7 percent), respectively (risk reduction, 65 percent; 95 percent confidence interval, 33 to 82 percent; P < 0.001); and death from all causes occurred in 9 patients (2.8 percent) and 22 patients (7.4 percent), respectively (risk reduction, 63 percent; 95 percent confidence interval, 19 to 83 percent; P = 0.01). Bleeding occurred in 71 patients in the aspirin group (35.0 percent), as compared with 49 patients in the placebo group (22.0 percent) (increase in risk, 55 percent; 95 percent confidence interval, 8 to 124 percent; P = 0.02); major bleeding occurred in 24 and 19 patients, respectively (increase in risk, 27 percent; 95 percent confidence interval, -30 to 132 percent; P = 0.43). CONCLUSIONS: In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves, the addition of aspirin to warfarin therapy reduced mortality, particularly mortality from vascular causes, together with major systemic embolism. Although there was some increase in bleeding, the risk of the combined treatment was more than offset by the considerable benefit.     

Physical activity and the risk of breast cancer

BACKGROUND: Because physical activity may affect hormonal concentrations and energy balance, we decided to investigate whether everyday exercise is related to the risk of breast cancer. METHODS: During 1974 to 1978 and 1977 to 1983, a total of 25,624 women, 20 to 54 years of age at entry, enrolled in health surveys and answered questionnaires about leisure-time and work activity. RESULTS: During a median follow-up of 13.7 years, we identified 351 cases of invasive breast cancer among the 25,624 women in the cohort. Greater leisure-time activity was associated with a reduced risk of breast cancer, after adjustments for age, body-mass index (the weight in kilograms divided by the square of the height in meters), height, parity, and county of residence (relative risk, 0.63; 95 percent confidence interval, 0.42 to 0.95), among women who exercised regularly, as compared with sedentary women (P for trend=0.04). In regularly exercising women, the reduction in risk was greater in premenopausal women than in postmenopausal women, and greater in younger women (<45 years at study entry) than in older women (> or =45 years) (relative risk, 0.38; 95 percent confidence interval, 0.19 to 0.79). In stratified analyses the risk of breast cancer was lowest in lean women (body-mass index, <22.8) who exercised at least four hours per week (relative risk, 0.28; 95 percent confidence interval, 0.11 to 0.70). The risk was also reduced with higher levels of activity at work, and again there was a more pronounced effect among premenopausal than postmenopausal women. CONCLUSIONS: Physical activity during leisure time and at work is associated with a reduced risk of breast cancer.     

Risk of leukemia after platinum-based chemotherapy for ovarian cancer

BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. METHODS: We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. RESULTS: Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.     

Radial scars in benign breast-biopsy specimens and the risk of breast cancer

BACKGROUND: Radial scars are benign breast lesions of uncertain clinical significance. In particular, it is not known whether these lesions alter the risk of breast cancer in women with benign breast disease. We conducted a case-control study of women who had benign breast lesions with or without radial scars. METHODS: We reviewed benign breast-biopsy specimens from 1396 women enrolled in the Nurses' Health Study, including 255 women in whom breast cancer subsequently developed and 1141 women without subsequent breast cancer (controls). The controls were matched to the women with subsequent breast cancer according to age and the year when the benign lesion was identified. The median follow-up after biopsy of the benign lesions was 12 years. RESULTS: Radial scars were identified in biopsy specimens from 99 women (7.1 percent). Most biopsy specimens with radial scars had only one radial scar (60.6 percent), and they tended to be incidental microscopical findings (median size, 4.0 mm). The women with radial scars had a risk of breast cancer that was almost twice the risk of the women without scars, regardless of the histologic type of benign breast disease (relative risk, 1.8; 95 percent confidence interval, 1.1 to 2.9). Among women who had proliferative disease without atypia as compared with women who had nonproliferative disease, the relative risk of breast cancer was 3.0 (95 percent confidence interval, 1.7 to 5.5) for those with radial scars and 1.5 (95 percent confidence interval, 1.1 to 2.1) for those without radial scars. Among women with atypical hyperplasia as compared with women with nonproliferative disease, the relative risk of breast cancer was 5.8 (95 percent confidence interval, 2.7 to 12.7) for those with radial scars and 3.8 (95 percent confidence interval, 2.4 to 5.9) for those without radial scars. CONCLUSIONS: Radial scars are an independent histologic risk factor for breast cancer.     

A prospective study of family history and the risk of colorectal cancer

BACKGROUND: A family history of colorectal cancer is recognized as a risk factor for the disease. However, as a result of the retrospective design of prior studies, the strength of this association is uncertain, particularly as it is influenced by characteristics of the person at risk and the affected family members. METHODS: We conducted a prospective study of 32,085 men and 87,031 women who had not previously been examined by colonoscopy or sigmoidoscopy and who provided data on first-degree relatives with colorectal cancer, diet, and other risk factors for the disease. During the follow-up period, colorectal cancer was diagnosed in 148 men and 315 women. RESULTS: The age-adjusted relative risk of colorectal cancer for men and women with affected first-degree relatives, as compared with those without a family history of the disease, was 1.72 (95 percent confidence interval, 1.34 to 2.19). The relative risk among study participants with two or more affected first-degree relatives was 2.75 (95 percent confidence interval, 1.34 to 5.63). For participants under the age of 45 years who had one or more affected first-degree relatives, the relative risk was 5.37 (95 percent confidence interval, 1.98 to 14.6), and the risk decreased with increasing age (P for trend, < 0.001). CONCLUSIONS: A family history of colorectal cancer is associated with an increased risk of the disease, especially among younger people.     

First-trimester growth and the risk of low birth weight

BACKGROUND: Previous studies have demonstrated a correlation between first-trimester size and birth weight. It is not known, however, whether low birth weight is related to first-trimester growth. We sought to determine whether the risk of low birth weight and birth weight that was low for gestational age is related to the size of the embryo or the fetus in the first trimester. METHODS: From a data base of ultrasound records of more than 30,000 pregnancies, we identified women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured. We examined the relation between the outcome of 4229 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth. RESULTS: A first-trimester crown-rump length that was two to six days smaller than expected was associated with an increased risk (as compared with a normal or slightly larger than expected crown-rump length) of a birth weight below 2500 g (relative risk, 1.8; 95 percent confidence interval, 1.3 to 2.4), a birth weight below 2500 g at term (relative risk, 2.3; 95 percent confidence interval, 1.4 to 3.8), a birth weight below the fifth percentile for gestational age (relative risk, 3.0; 95 percent confidence interval, 2.0 to 4.4), and delivery between 24 and 32 weeks of gestation (relative risk, 2.1; 95 percent confidence interval, 1.1 to 4.0), but not with delivery between 33 and 36 weeks (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.5). CONCLUSIONS: Suboptimal first-trimester growth may be associated with low birth weight, low birth-weight percentile, and premature delivery.     

A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones

BACKGROUND: A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones. However, a high intake of calcium can reduce the urinary excretion of oxalate, which is thought to lower the risk. The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination. METHODS: We conducted a prospective study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men, 40 to 75 years of age, who had no history of kidney stones. Dietary calcium was measured by means of a semiquantitative food-frequency questionnaire in 1986. During four years of follow-up, 505 cases of kidney stones were documented. RESULTS: After adjustment for age, dietary calcium intake was inversely associated with the risk of kidney stones; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 (95 percent confidence interval, 0.43 to 0.73; P for trend, < 0.001). This reduction in risk decreased only slightly (relative risk, 0.66; 95 percent confidence interval, 0.49 to 0.90) after further adjustment for other potential risk factors, including alcohol consumption and dietary intake of animal protein, potassium, and fluid. Intake of animal protein was directly associated with the risk of stone formation (relative risk for men with the highest intake as compared with those with the lowest, 1.33; 95 percent confidence interval, 1.00 to 1.77); potassium intake (relative risk, 0.49; 95 percent confidence interval, 0.35 to 0.68) and fluid intake (relative risk, 0.71; 95 percent confidence interval, 0.52 to 0.97) were inversely related to the risk of kidney stones. CONCLUSIONS: A high dietary calcium intake decreases the risk of symptomatic kidney stones.     

Falls, injuries due to falls, and the risk of admission to a nursing home

BACKGROUND: Falls warrant investigation as a risk factor for nursing home admission because falls are common and are associated with functional disability and because they may be preventable. METHODS: We conducted a prospective study of a probability sample of 1103 people over 71 years of age who were living in the community. Data on demographic and medical characteristics, use of health care, and cognitive, functional, psychological, and social functioning were obtained at base line and one year later during assessments in the participants' homes. The primary outcome studied was the number of days from the initial assessment to a first long-term admission to a skilled-nursing facility during three years of follow-up. Patients were assigned to four categories during follow-up: those who had no falls, those who had one fall without serious injury, those who had two or more falls without serious injury, and those who had at least one fall causing serious injury. RESULTS: A total of 133 participants (12.1 percent) had long-term admissions to nursing homes. In an unadjusted model, the risk of admission increased progressively, as compared with that for the patients with no falls, for those with a single noninjurious fall (relative risk, 4.9; 95 percent confidence interval, 3.2 to 7.5), those with multiple noninjurious falls (relative risk, 8.5; 95 percent confidence interval, 3.4 to 21.2), and those with at least one fall causing serious injury (relative risk, 19.9; 95 percent confidence interval, 12.2 to 32.6). Adjustment for other risk factors lowered these ratios to 3.1 (95 percent confidence interval, 1.9 to 4.9) for one noninjurious fall, 5.5 (95 percent confidence interval, 2.1 to 14.2) for two or more noninjurious falls, and 10.2 (95 percent confidence interval, 5.8 to 17.9) for at least one fall causing serious injury, but the association between falls and admission to a nursing home remained strong and significant. The population attributable risk of long-term admission to a nursing home for these three groups (the proportion of admissions directly attributable to the three categories of falls) was 13 percent, 3 percent, and 10 percent, respectively. CONCLUSIONS: Among older people living in the community falls are a strong predictor of placement in a skilled-nursing facility; interventions that prevent falls and their sequelae may therefore delay or reduce the frequency of nursing home admissions.     

A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group

BACKGROUND: The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. METHODS: We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. RESULTS: Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). CONCLUSIONS: The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.     

p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.     

Germ line polymorphisms in cytochrome-P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility

We describe here a case-control study to identify associations between polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) and cytochrome P-450 1A1 (CYP1A1) genes and susceptibility to endometrial cancer. Accordingly, genotype frequencies in 80 endometrial carcinoma patients were compared with frequencies in 60 controls. DNA analysis suggest a significantly increased endometrial cancer risk with an alanine to valine substitution at nucleotide 677 of MTHFR gene with an odds ratio of 2.8 (95% confidence interval: 1.36-6.14, P = 0.002). Moreover, the tumors from patients with the valine allele were more undifferentiated (P = 0.03). On the other hand, a recently described mutation in exon 7 of CYP1A1 gene (threonine exchanged to asparagine in codon 461) showed a strong association with endometrial cancer risk with an odds ratio of 6.36 (95% confidence interval: 1.99-26.5, P = 0.0004). Thus, this study suggests that polymorphisms at MTHFR and a novel CYP1A1 variant could influence susceptibility to endometrial cancer, although larger sample sizes would be required to corroborate these findings.     

Relapsing pancreatitis due to juxta-pancreatic duodenal duplication cyst with pancreatic ductal communication

BACKGROUND: Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer. PURPOSE: The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer. METHODS: Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort. RESULTS: In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890). CONCLUSIONS: These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer.     

Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation

Using data from the Health Professionals Follow-Up Study, we prospectively examined the relationships between height, body mass index, waist and hip circumferences, and risk of total and advanced (extraprostatic and metastatic) prostate cancer. In addition, we assessed adiposity during childhood, adolescence, and early, middle, and late adulthood using pictograms in relation to prostate cancer risk. Between 1986 and 1994, 1,369 cases of prostate cancer (excluding stage A1) were confirmed in 47,781 men. Adult body mass index and waist and hip circumferences were not appreciably related to risk of total prostate cancer or advanced prostate cancer. In contrast, preadult (age 10) obesity assessed in 33,336 men in 1988 was prospectively related to lower risk of advanced [relative risk (RR) = 0.72 with 95% confidence interval (CI) = 0.47-1.10, between high and low quintiles; P(trend) = 0.06] and metastatic prostate cancer (RR = 0.38 with 95% CI = 0.19-0.77; P(trend) = 0.004). For the advanced lesions, an association was observed with height (RR = 1.68 with 95% CI = 1.16-2.43 for men 74 inches or taller, relative to men 68 inches or shorter; P(trend) = 0.01). In an analysis limited to particularly aggressive forms of prostate cancer, i.e., cases found to be metastatic at time of diagnosis between 1988 and 1994 after a negative digital rectal examination in 1988, we found that obesity at ages 5 and 10 had a strong inverse association (RR = 0.16 with 95% CI = 0.05-0.54, between high and low quintiles at age 10) and that tallness had a strong direct association with risk of metastatic disease (RR = 2.29 with 95% CI = 1.04-5.05, for height > or = 74 inches versus < or = 68 inches). Our findings suggest that the preadult hormonal milieu, as reflected in attained height and childhood obesity, may have a strong influence on prostate carcinogenesis.     

Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice

A case-control study was conducted between 1992 and 1996 in six Italian areas. It included 537 women with colon cancer, 291 women with rectal cancer and 2081 control women in hospital for acute conditions, unrelated to hormonal or gynaecological diseases. A higher age at menopause was associated with increased colon cancer risk (odds ratio (OR) for > or = 53 years compared with < 50 years = 1.39, 95% confidence interval (CI) 1.04-1.87). Among parous women, a significant trend of decreasing colon cancer risk with increasing number of births was seen for colon (OR for > or = 4 births compared with 1 birth = 0.62, 95% CI 0.42-0.90), but not for rectal cancer. Nulliparous women, however, were at lower risk than women with a single birth, and age at first birth was directly associated with risk. While oral contraceptive use showed no significant influence, ever users of hormone replacement therapy had a reduced risk of rectal cancer (OR = 0.56, 95% CI 0.31-1.01). Thus, the association of colorectal cancer with reproductive and menstrual factors is neither strong nor consistent.     

Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer

BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 percent reduction in the rate of recurrence (relative risk, 0.67; 95 percent confidence interval, 0.50 to 0.90) and a 29 percent reduction in mortality from breast cancer (relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.     

Prospective assessment of the hepatic perfusion index in patients with colorectal cancer

BACKGROUND: This prospective study was designed to test the hypothesis that abnormal liver blood flow is related to poor prognosis in patients with colorectal cancer. METHODS: The hepatic perfusion index (HPI), measured by dynamic hepatic scintigraphy, was assessed in 202 patients with colorectal cancer. Assessment for overt hepatic metastasis included liver palpation at laparotomy and perioperative computed tomography (CT). Follow-up at a dedicated clinic included regular abdominal ultrasonography and CT. RESULTS: The HPI was abnormal (greater than 0.37) in 92 (88 per cent) of 105 patients with overt liver metastases. Of 89 patients with no evidence of overt metastases or residual tumour after primary resection, 52 had an abnormal and 37 a normal HPI. At a median follow-up of 39 (range 13-76) months, 25 of 38 patients with recurrence had an abnormal HPI. Some 31 of 45 patients who died had an abnormal HPI. The HPI predicted overall recurrence (P=0.04, log rank test). Multivariate analysis showed the HPI was independent of Dukes stage for predicting disease-free survival (P=0.04, relative risk 1.94 (95 per cent confidence interval (c.i.) 1.03-3.67)) but this just failed to attain significance for overall survival (P=0.055, relative hazard 1.88 (95 per cent c.i. 1.00-3.58)). CONCLUSION: The HPI predicts a poor outcome in patients with colorectal cancer and may be useful in patient selection for adjuvant chemotherapy.     

Reproductive factors and risk of brain, colon, and other malignancies in Iowa (United States)

The influence of parity on the risk of cancers of the female breast and reproductive organs is well established. However, non-reproductive sites have received less attention. Mail questionnaire data gathered from incident female cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers), and 821 population-based controls in Iowa (United States) were used to measure the effect of parity and age at first birth on risk of these malignancies. Relative to nulliparous women, ever-parous women were at significantly decreased risk of brain cancer (odds ratio [OR] = 0.44, 95 percent confidence interval [CI] = 0.3-0.7) and of colon cancer (OR = 0.67, CI = 0.5-0.97), after adjustment for age and other risk factors. The OR for the other sites did not differ significantly from 1.0. The lower risk of brain cancer among parous women was similar in younger and older age groups, in patients diagnosed with glioblastoma and astrocytoma, and among ever- and never-smokers. The findings for colon cancer are consistent with observations from other studies. In the context of limited laboratory and clinical evidence implicating hormones in brain neoplasia, these findings may suggest a role for hormonal factors in brain cancer etiology. Hormonal factors deserve more detailed future consideration as risk factors in brain cancer.     

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.