Factors associated wih high and low risk of cervical neoplasia.

Among 34,318 participants in a cervical cancer screening program conducted in 12 California counties between 1975 and 1979, biopsy-proved cervical neoplasia was found in 166. These women served as cases in a case-control study to investigate the association of selected characteristics with the risk of cervical dysplasia and/or cancer. A random sample of program participants with only negative cytologic tests formed the control group. The following factors showed no association with cervical neoplasia: ethnic affiliation, age at menarche, age at first marriage, age at first pregnancy, age at birth of first child, mean number of children, and ever use of oral contraceptives. Risk of cervical neoplasia was increased in women who were less than 40 years of age; were of poverty or low income status; and were separated, divorce, or widowed. A decrease in risk was associated with nulliparity, ever use of estrogens for relief of menopausal symptoms, and ever use of the diaphragm.

Epithelial ovarian cancer and the ability to conceive.

Relationships between ovarian cancer and ability to conceive were explored in a case-control study of 188 women with histologically confirmed epithelial ovarian cancer and 539 control women in the San Francisco Bay Area. Control women consisted of two groups: those hospitalized without cancer, matched to cases by age, race, and hospital of diagnosis (n = 280); and those selected from the general population by random digital dialing, matched to cases by age, race, and telephone prefix (n = 259). Ovarian cancer risk among nulliparous (but not parous) women was positively associated with a history of unsuccessful attempts to conceive, of physician-diagnosed infertility, and of doubts about ability to conceive. Among all women, risk increased with increasing years of unprotected intercourse (P value for trend = 0.02). Risk among women having 10 or more yr of unprotected intercourse was 1.8 relative to that among women having less than 2 such yr (P = 0.01). This association was independent of parity, oral contraceptive use, and estimated years of ovulation, each associated with ovarian cancer. Further, duration of unprotected intercourse combined multiplicatively with each of these latter characteristics in increasing ovarian cancer risk. For example, while cancer risk exhibited a 2-fold range from lowest to highest years of unprotected intercourse and a 4-fold range from lowest to highest years of ovulation, risk among women in the highest joint category of these characteristics was 8 times that of women in the lowest category. We believe that some abnormality of ovulation that reduces the likelihood of conception plays a role in epithelial ovarian cancer.

Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality.

BACKGROUND: Although medical textbooks usually classify fasting plasma glucose <70 or 80 mg/dL (<3.89 or 4.44 mmol/L) as abnormal, the prognosis for patients with low fasting plasma glucose is unclear. METHODS AND RESULTS: We conducted prospective cohort studies among 40 069 men and women to investigate the association between fasting plasma glucose levels and cardiovascular disease and all-cause mortality. We documented a U-shaped relation between fasting plasma glucose and mortality. In addition to diabetes and impaired fasting glucose levels, low fasting plasma glucose levels were also associated with high mortality. After multivariate adjustment for age, sex, study population, ethnicity, current smoking status, high blood pressure, total cholesterol, body mass index, triglycerides, history of cardiovascular disease and cancer, and a family history of cardiovascular disease, patients with fasting plasma glucose <70 mg/dL (<3.89 mmol/L) had a 3.3-fold increased risk of cardiovascular disease mortality, and patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) (tests for trend P<0.0001). Participants with low fasting plasma glucose levels also had increased risk of all-cause mortality (test for trend P<0.0001). CONCLUSIONS: Participants with low fasting plasma glucose levels had a high risk of cardiovascular disease and all-cause mortality.

Associations between cardiorespiratory fitness and C-reactive protein in men.

OBJECTIVE: This study examined the association between cardiorespiratory fitness and C-reactive protein (CRP), with adjustment for weight and within weight categories. METHODS AND RESULTS: We calculated median and adjusted geometric mean CRP levels, percentages of individuals with an elevated CRP (> or =2.00 mg/L), and odds ratios of elevated CRP across 5 levels of cardiorespiratory fitness for 722 men. CRP values were adjusted for age, body mass index, vitamin use, statin medication use, aspirin use, the presence of inflammatory disease, cardiovascular disease, and diabetes, and smoking habit. We found an inverse association of CRP across fitness levels (P for trend<0.001), with the highest adjusted CRP value in the lowest fitness quintile (1.64 [1.27 to 2.11] mg/L) and the lowest adjusted CRP value in the highest fitness quintile (0.70 [0.60 to 0.80] mg/L). Similar results were found for the prevalence of elevated CRP across fitness quintiles. We used logistic regression to model the adjusted odds for elevated CRP and found that compared with the referent first quintile, the second (odds ratio [OR] 0.43, 95% CI 0.22 to 0.85), third (OR 0.33, 95% CI 0.17 to 0.65), fourth (OR 0.23, 95% CI 0.12 to 0.47), and fifth (OR 0.17, 95% CI 0.08 to 0.37) quintiles of fitness had significantly lower odds of elevated CRP. Similar results were found when examining the CRP-fitness relation within categories of body fatness (normal weight, overweight, and obese) and waist girth (<102 or > or =102 cm). CONCLUSIONS: Cardiorespiratory fitness levels were inversely associated with CRP values and the prevalence of elevated CRP values in this sample of men from the Aerobics Center Longitudinal Study.

Alcohol intake and incidence of type 2 diabetes in men.

OBJECTIVE: To evaluate the relation between alcohol intake and incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: This prospective study included 8,663 men with fasting plasma glucose measurements from at least two medical examinations. Alcohol intake was classified into five groups: nondrinkers and four quartiles (Qs) of drinkers according to the amount of alcohol intake. Type 2 diabetes was diagnosed by 1997 American Diabetes Association criteria. RESULTS: There were 149 incident cases of type 2 diabetes during 52,588 person-years of follow-up. There was a U-shaped association between alcohol intake and diabetes, with the lowest incidence of diabetes at Q2 (61.9-122.7 g/week). As compared with Q2, men in Q3 and Q4 had a 2.2- (95% CI 1.2-3.9, P = 0.01) and 2.4-fold (1.4-4.4, P<0.01) risk of developing diabetes, while nondrinkers and men in Q1 had 1.8- (1.0-3.3, P<0.05) and 1.4-fold (0.7-2.6, P = 0.34) higher risk of diabetes, respectively. These associations persisted after adjustment for age, fasting plasma glucose, smoking, BMI, blood pressure, serum triglyceride concentration, cardiorespiratory fitness, HDL cholesterol, waist circumference, and parental diabetes. CONCLUSIONS: We observed an elevated risk of developing type 2 diabetes in nondrinkers and men with high alcohol intakes, when compared with men who reported moderate alcohol intake. Men with a high alcohol intake may be able to reduce their risk of developing type 2 diabetes if they drink less.

Usefulness of cardiorespiratory fitness as a predictor of all-cause and cardiovascular disease mortality in men with systemic hypertension.

There is an inverse gradient of mortality across levels of cardiorespiratory fitness in healthy adults; however, the association of fitness to mortality in persons with comorbidities such as hypertension is not fully understood. This study quantifies the relation of cardiorespiratory fitness to all-cause mortality and cardiovascular disease (CVD) mortality in hypertensive men. In this observational cohort study, we calculated death rates for low, moderate, and high fitness categories in normotensive (n = 15,726) and hypertensive (n = 3,184) men, and in men without a history of hypertension but with elevated blood pressure (BP) (systolic BP > or = 140 or diastolic BP > or = 90 mm Hg) at baseline (n = 3,257). The participants were 22,167 men (average age 42.6 +/- 9.2 years [mean +/- SD]) who underwent a medical examination that included a maximal exercise test during 1970 to 1993, with mortality follow-up to December 31, 1994. We identified 628 deaths (188 from CVD) during 224,173 man-years of observation. There was an inverse linear trend across fitness groups for all-cause and CVD mortality. The relative risk (95% confidence interval [CI]), using the low fitness group as reference, for all-cause mortality in hypertensive men was 0.45 (95% CI 0.31 to 0.65) and 0.42 (95% CI 0.27 to 0.66) for moderate and high fitness groups, respectively, and in men with elevated BP, 0.49 (95% CI 0.34 to 0.70) and 0.44 (95% CI 0.29 to 0.68) for moderate and high fitness groups, respectively. The pattern of results was similar for CVD mortality. There was an inverse linear relation between fitness and death rate for all-cause mortality in both the uncontrolled and controlled hypertensive groups. This study provides evidence that moderate to high levels of cardiorespiratory fitness provide protection against all-cause and CVD mortality in hypertensive men and men without a history of hypertension but with elevated BP at examination.

Physical activity, physical fitness, and all-cause and cancer mortality: a prospective study of men and women.

We studied physical fitness and physical activity in relation to all-cause and cancer mortality in a cohort of 7080 women and 25,341 men examined at the Cooper Clinic in Dallas, Texas, during 1970 to 1989. Physical fitness was assessed at baseline by a maximal treadmill exercise test, while physical activity was self-reported on the attendant health habits questionnaire. Both men and women averaged about 43 years of age at baseline (range, 20 to 88 years), and they were followed for approximately 8 years on average. Through the end of 1989, the women contributed 52,982 person-years of observation and incurred 89 deaths, including 44 deaths due to cancer. The men contributed 211,996 person-years and incurred 601 deaths, with 179 due to cancer. After adjustment for baseline differences in age, examination year, cigarette habit, chronic illnesses, and electrocardiogram abnormalities, we found a strong inverse association between risk of all-cause mortality and level of physical fitness in both men and women (P for trend < 0.001). Physically active men also were at lower risk of all-cause mortality than were sedentary ones (P for trend = 0.01). Among women, however, self-reported physical activity was not significantly related to risk of death from all causes. The risk of mortality from cancer declined sharply across increasing levels of fitness among men (P for trend < 0.001), whereas among women the gradient was suggestive but not significant (P for trend = 0.07). Physically active men also were at lower risk of death from cancer than were sedentary men (P for trend = 0.002), but among women physical activity was unrelated to cancer mortality.

Physical fitness and clustering of risk factors associated with the metabolic syndrome.

PURPOSE: The purposes of this study were to 1) assess the prevalence of clustering of metabolic markers of the MS in a defined population and 2) determine the association between CRF and such clustering in a large group of adult men (N = 15,537) and women (N = 3,899). METHODS: Metabolic markers of the MS included systolic blood pressure (BP) > or = 140 mm Hg, serum triglycerides > or = 150 mg x dL(-1), fasting blood glucose > or = 110 mg x dL(-1), and elevated central adiposity (waist circumference > 100 cm). Cardiorespiratory fitness was defined as total time on a maximal treadmill exercise test. The cohort was grouped by the number of metabolic abnormalities and level of CRF. Associations between CRF and the number of metabolic abnormalities were assessed using proportional odds logit models. RESULTS: Among men, the age-adjusted cumulative odds ratio for abnormal markers of the MS was 3.0 (95% C.I. 2.7-3.4; P < 0.001) for the least-fit men when compared with moderately-fit ones, and 10.1 (95% C.I. 9.1-11.2; P < 0.001) when compared with the most-fit men. Among women, the age-adjusted cumulative odds ratio was 2.7 (95% C.I. 2.1-3.5; P < 0.001) for the least-fit women when compared with moderately-fit ones, and 4.9 (95% C.I. 3.8-6.3; P < 0.001) when compared with the most-fit women. CONCLUSIONS: These cross-sectional results suggest that low CRF is associated with an increased clustering of the metabolic abnormalities associated with the MS in both adult men and women and support the need for future prospective analyses.

Evaluating the reproducibility and validity of the Aerobic Adaptation Test.

PURPOSE: To examine the reproducibility and validity of a new submaximal, ramped cycle ergometer testing methodology known as the Aerobic Adaptation Test (AAT), which attempts to detect changes in submaximal work capacity and minimize participant discomfort. METHODS: 36 sedentary men (mean age = 48.1 +/- 10.2 yr [SD]) and 22 sedentary women (mean age = 51.9 +/- 10.2 yr [SD]) participated in the study. To test reproducibility, participants were tested twice with an average of 20 d between tests (+/-15 d). To test validity, participants were tested before and after a 6-month physical activity intervention, and outcomes were compared with standard measures of fitness (exercise time and oxygen consumption at 70% max heart rate). The main outcome variable of the AAT was work output (W) over a period of 3 min after reaching 70% maximal heart rate. RESULTS: The average work output at 70% HRmax was highly reproducible, with a test-retest reliability of rho = 0.85 (P < 0.001). Average work output at 70% HRmax significantly increased after 6 months of physical activity intervention (87.8 +/- 32.9 W vs 95.5 +/- 37.9 W, P = 0.002), and changes in average work output at 70% HRmax correlated with changes in exercise time to elicit 70% HRmax (r = 0.87, P < 0.001) as well as changes in VO2 at 70% HRmax (r = 0.75, P < 0.001). Thus, the AAT appears to be a valid measure of submaximal work capacity. CONCLUSIONS: The AAT is a reproducible and valid measure of submaximal work capacity that can serve as an effective means to evaluate physical activity interventions.

Changes in physical activity and other lifeway patterns influencing longevity.

We studied the adoption or maintenance of physical activity and other optional lifeway patterns for their influence on mortality rates of Harvard College alumni. Men aged 45-84 in 1977, surveyed by questionnaire in 1962 or 1966 and again in 1977, were followed from 1977 through 1988 or to age 90. Of 14,786 alumni, 2,343 died in 165,402 man-years of follow-up. Relative risks of death, standardized for potential confounding influences, for men who between questionnaires increased their physical activity through walking, stair climbing, and sports or recreational activities to 1,500 kcal or more per wk were 0.72 (95% confidence interval 0.64-0.82), compared with 1.00 for men who remained less active. Corresponding relative risks for men who adopted moderately vigorous sports play (> or = 4.5 METs) were 0.73 (0.65-0.81) vs 1.00 for men not adopting such sports; and for cigarette smokers who quit, 0.74 (0.65-0.84) vs 1.00 for persistent smokers. Men with recently diagnosed hypertension had a lower death risk than long-term hypertensives (0.80; 0.70-0.92), as did men with consistent normotension (0.52; 0.47-0.58). Changes in body-mass index had little influence on mortality during follow-up. These findings fit the hypothesis that adopting a physically active lifeway, quitting cigarette smoking, and remaining normotensive independently delay all-cause mortality and extend longevity.

Influences of cardiorespiratory fitness levels and other predictors on cardiovascular disease mortality in men.

PURPOSE: This investigation quantifies the relation between cardiorespiratory fitness levels and cardiovascular disease (CVD) mortality within strata of other CVD predictors. METHODS: Participants included 25,341 male Cooper Clinic patients who underwent a maximal graded exercise test. CVD death rates were determined for low (least fit one-fifth), moderate (next two-fifths), and high (top two-fifths) cardiorespiratory fitness categories by strata of smoking habit, blood cholesterol level, resting blood pressure, and health status. There were 226 cardiovascular deaths during 211,996 man-years of follow-up. RESULTS: For individuals with none of the major CVD predictors (smoking, elevated resting systolic blood pressure, elevated blood cholesterol), there was a strong inverse relation (P = 0.001) between fitness level and CVD mortality. An inverse relation between CVD mortality and fitness level was seen within strata of cholesterol levels and health status. No evidence of a trend (P = 0.60) for decreased mortality was seen across fitness levels for individuals with elevated systolic blood pressure; however, a strong inverse gradient (P < 0.001) was seen across fitness levels for individuals with normal systolic blood pressure. There was a tendency for association between high levels of fitness and decreased CVD mortality in smokers compared with low and moderately fit smokers (P < 0.076). There was no significant association between level of fitness and CVD mortality for individuals with multiple (two or more) predictors (P = 0.325). Approximately 20% of the 226 CVD deaths in the population studied were attributed to low fitness level. CONCLUSIONS: Moderate and high levels of cardiorespiratory fitness seem to provide some protection from CVD mortality, even in the presence of well established CVD predictors.

Six-month physical activity and fitness changes in Project Active, a randomized trial.

PURPOSE: Project Active is a randomized clinical trial (N = 235) comparing a lifestyle physical activity program with a structured exercise program in changing physical activity (total energy expenditure [kcal.kg-1.d-1]) and cardiorespiratory fitness (VO2peak in mL.kg-1.min-1). METHODS: Sedentary but healthy adults (N = 235) aged 35-60 years received 6 months of intensive intervention. RESULTS: Analysis of covariance (ANCOVA), adjusting for baseline measure, age, gender, body mass index (BMI), cohort, and ethnicity, showed that at 6 months both lifestyle and structured groups significantly increased energy expenditure over baseline (P < 0.001). The mean increases +/- SE, 1.53 +/- 0.19 kcal.kg-1.d-1 for the lifestyle group and 1.34 +/- 0.20 kcal.kg-1 d-1 for the structured group, were not significantly different between groups (P = 0.49). For cardiorespiratory fitness, both groups had significant increases from baseline (P < 0.001). Mean increases +/- SE were 1.58 +/- 0.33 mL.kg-1.min-1 and 3.64 +/- 0.33 mL.kg-1.min-1 for the lifestyle and structured groups, respectively. This was significantly greater in the structured group (P < 0.001). We also studied changes in intensity of physical activity. Both groups significantly increased moderate intensity activity from baseline, but the increase was significantly greater in the lifestyle group than the structured group (P = 0.02). In contrast, the structured group increased its hard activity more than the lifestyle group, but the difference was not significantly different (P = 0.02). In contrast, the structured group increased its hard increased (P < 0.01) for both groups by 0.25 kcal.kg-1.d-1. CONCLUSION: Both intervention approaches are effective for increasing physical activity and fitness over a 6-month period in initially sedentary men and women.

Characteristics that predict risk of breast cancer before and after the menopause.

In a case-control study of 1868 breast cancer patients and 3391 control patients we searched for characteristics that predicted risk of breast cancer diagnosed before and after menopause. Common to increased risk of this disease in both periods of womanhood were: early menarche and late menopause; delayed marriage and first childbirth; more nulliparity or reduced gravidity and parity; reduced frequency of abortions; shorter overall child-bearing interval; more advanced education, higher socioeconomic status, and more contraceptive usage; and familial tendencies toward the disease. Breast cancer patients diagnosed before menopause were leaner than controls at age 20 and at time of diagnosis, but breast cancer risk in the postmenopausal period was related to increased weight-for-height at diagnosis and greater weight-for-height at diagnosis and greater weight gain since age 20. Postmenopausal breast cancer patients had a longer interval between first and second childbirths. Frequency and duration of the gravid state, inversely related to breast cancer risk, were largely dependent on contraceptive practices rather than unexplained infertility per se. Whether the breast cancer reaches diagnosis before or after menopause, the bulk of evidence examined here supports the view that it has a common cause and is subject to modifying influences over the long period of cancer latency.

PIP: Case-control studies are reported of 1868 breast cancer patients and 3391 unaffected women from the San Francisco Bay Area that identify clues to the etiology of breast cancer and distinguish characteristics of patients with premenopausal, paramenopausal, or postmenopausal dates of 1st diagnosis. Patients with breast cancer diagnosed during 1970-1977 were interviewed at home, as were twice as many control patients from the same hospitals matched to the cancer patients by age (within 5 years), race (white or black), and time of hospitalization (within 7 months). Rates of participation through interview were about 70%, somewhat higher for breast patients than for control patients. Common to increased risk of breast cancer in periods of womanhood were: early menarche and late menopause; delayed marriage and 1st childbirth; more nulliparity or reduced gravidity and parity; reduced frequency of abortions; shorter overall childbearing interval; more advanced education, higher socioeconomic status, and more contraceptive usage; and familial tendencies toward the disease. Breast cancer patients diagnosed before menopause were leaner than controls at age 20 and at time of diagnosis, but breast cancer risk in the postmenopausal period was related to increased weight-for-height at diagnosis and greater weight gain since age 20. Postmenopausal breast cancer patients had a longer interval between 1st and 2nd childbirths. Frequency and duration of the gravid state, inversely related to breast cancer risk, were largely dependent on contraceptive practices rather than unexplained infertility per se. Whether the breast cancer reaches diagnosis before or following menopause, the bulk of the evidence examined supports the view that it has a common cause and is subject to modifying influences over the long period of cancer latency.

Physical activity and health of college men: longitudinal observations.

The College Alumni Health Study has examined host and environmental characteristics in youth and adult life as they relate to subsequent development of specific chronic diseases. Campus archives have provided physical, psychological, and social data on some 57,500 men and women who were born between 1896 and 1934, and who entered Harvard College or the University of Pennsylvania between 1916 and 1950, generally at age 17-20 years. These college data have been studied subsequently to assess whether characteristics in youth predisposed students to chronic diseases (nonfatal and fatal) later in life. Follow-up questionnaires, mailed to alumni, generally aged 35-85 years, in the 1960s, 1970s, 1980s, and 1990s have provided mid-life information on the health status and health habits of survivors, and official death certificates have provided data on decedents. This information has been studied, in fashion similar to the college data, for personal characteristics and ways of living that influenced health and longevity of these middle-aged and elderly men. Longitudinal observations continue today, in search of causes of specific chronic diseases.

Combined effect of childbearing, menstrual events, and body size on age-specific breast cancer risk.

Pike et al. (Nature 1983;303:767-70) and Moolgavkar et al. (JNCI 1980;65:59-69) proposed quantitative theories for the effect on age-specific breast cancer risk of ages at menarche, first childbirth, and menopause. Here the incidence rate functions predicted by these theories are fit to data for 1,884 women of all ages with breast cancer and 3,432 matched controls admitted to San Francisco Bay area hospitals in 1970-1977. A third function describing age-specific breast cancer risk based on the timing of childbearing and menstrual events is presented, and its fit to the data is compared with that of the functions of Pike et al. and Moolgavkar et al. None of the three fully accounted for the protective effects of early age at first childbirth in premenopausal women or of early age at menopause in parous postmenopausal women. To account for the effects of total parity and body mass (Quetelet) index on risk of breast cancer occurrence, the authors developed a fourth incidence rate function by extending the third. Goodness of fit to the data of the fourth function is demonstrated. Age-specific relative risks of breast cancer according to childbearing, menstrual events, and body size are estimated from the fourth function. The main qualitative findings are that 1) the protective effects of late menarche and of early first full-term pregnancy are greater in premenopausal than in postmenopausal women; 2) first full-term pregnancy initially boosts the level of risk, but incidence rates increase with age more slowly thereafter; 3) among the parous, multiparity is protective both in premenopausal and postmenopausal women, regardless of age at first full-term pregnancy; 4) both nulliparous and lean women are more protected by early menopause than are parous and overweight women; 5) increased body mass index is protective before, but detrimental after, menopause; and 6) postmenopausal incidence rates increase with age more rapidly among overweight than among lean women.

PIP: The authors estimate "age-specific relative risks of breast cancer according to childbearing, menstrual events, and body size...." Consideration is given to the effects of age at menarche, parity, age at first birth, menopause, and body weight. Data are for 1,884 women of all ages with breast cancer and 3,432 matched controls admitted to hospitals in the San Francisco, California, area during the period 1970-1977.

Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes.

BACKGROUND: Although physical activity is recommended as a basic treatment for patients with diabetes, its long-term association with mortality in these patients is unknown. OBJECTIVE: To evaluate the association of low cardiorespiratory fitness and physical inactivity with mortality in men with type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Preventive medicine clinic. PATIENTS: 1263 men (50+/-10 years of age) with type 2 diabetes who received a thorough medical examination between 1970 and 1993 and were followed for mortality up to 31 December 1994. MEASUREMENTS: Cardiorespiratory fitness measured by a maximal exercise test, self-reported physical inactivity at baseline, and subsequent death determined by using the National Death Index. RESULTS: During an average follow-up of 12 years, 180 patients died. After adjustment for age, baseline cardiovascular disease, fasting plasma glucose level, high cholesterol level, overweight, current smoking, high blood pressure, and parental history of cardiovascular disease, men in the low-fitness group had an adjusted risk for all-cause mortality of 2.1 (95% CI, 1.5 to 2.9) compared with fit men. Men who reported being physically inactive had an adjusted risk for mortality that was 1.7-fold (CI, 1.2-fold to 2.3-fold) higher than that in men who reported being physically active. CONCLUSIONS: Low cardiorespiratory fitness and physical inactivity are independent predictors of all-cause mortality in men with type 2 diabetes. Physicians should encourage patients with type 2 diabetes to participate in regular physical activity and improve cardiorespiratory fitness.

Epidemiologic characteristics of breast cancer in three menopausal stages: preliminary findings.

A preliminary analysis of data from 1,477 patients with breast cancer and 2,695 control women examined potential characteristics of high risk for breast cancer to determine whether prediction differed depending on whether the women were premenopausal, paramenopausal (intermediate), or postmenopausal. Since information was not yet available on real or presumed menopausal status, women were characterized by age: women less than 45 years as premenopausal; women from 45 through 54 years as paramenopausal; and women 55 years and older as postmenopausal. Height, weight at age 20, number of stillbirths, number of abortions, and history of cancer of any site in the subject's mother did not affect the risk of breast cancer. Generally, highest level of education, number of pregnancies, and number of live births seemed to predict risk of breast cancer. Weightbody mass index, age at menarche, and age at first pregnancy may predict breast cancer risk differently depending on the menopausal stage in which onset occurs.

Work activity and fatal heart attack studied by multiple logistic risk analysis.

A group of 3975 San Francisco longshoremen in cohorts classified annually by work activity (WA) was followed for fatal heart attack (FHA) over a 22-year period. In 57,632 person-years of follow-up, 410 men died from heart attack. A multi-factor logistic analysis was used to study work energy output adjusted for age, race, systolic blood pressure, smoking, body mass index, glucose intolerance and EKG status as predictors of FHA. After adjustment for these factors, men with a high WA of 7 kcal/min above basal metabolism at the beginning of a yearly follow-up period had a FHA rate about one-half the rate for men in the lowest WA category of 1 kcal/min above basal metabolism (p = 0.0003). In addition, the predictability of average WA during the four years preceding a yearly follow-up period was isolated to see if the lower risk associated with high WA derives from selective factors. After adjustment for factors described above and also for rate of change in WA used to represent selective factors, subjects with WA of 7 kcal/min still had about one-half the FHA rate observed for men at the lowest WA level (p = 0.0006). The findings from these and other phases of the analysis are consistent with the hypothesis that a substantial protective effect against FHA results from vigorous physical exertion.

Cancer risk as related to use of oral contraceptives during fertile years.

A case-control study of 452 breast cancer patients, aged less than 50 years, and 872 age-, race-, and religion-matched control patients generated relative risk estimates of breast cancer associated with oral contraceptive practices. The relative risk of breast cancer from ever-use of oral contraceptives was 1.1, not significant. Relative risks did not differ by age, interval since first use, interval since last use, or time periods in which steroid compounds differed in composition and potency. However, the relative risks of breast cancer from current use, from 2 to 4 years of ever-use, from 6 or more years of use by women with prior benign breast disease, and from use before first childbirth were increased significantly. The findings suggest the malignant process may be quickened if transformed cells are present during oral contraceptive use. Yet, the findings neither indicate that oral contraception induces breast cancer nor do they exonerate female steroid hormones. The findings do encourage continued surveillance of steroid contraception for cancer induction or promotion. In addition to duration of oral contraceptive use and other measures of dose response, future observations should pay especial attention to use by women before first childbirth and by women with already established benign breast disease.