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Biomedical subjects

D J Hunter

Publications and source records attributed to D J Hunter.

At least 181 records · Page 10Linked to original sources

Reduced aliquot size for a plasma organochlorine assay for use in epidemiological studies.

Because archived blood specimens are an important but limited resource for conducting epidemiological studies using biomarkers, it is important to develop analytical techniques that minimize the amount of sample needed. We modified an established 1.0-ml blood plasma organochlorine assay to use smaller volumes. We assessed its utility by comparing the accuracy and precision of measurements obtained with different-sized aliquots of spiked plasma from three pools of known concentration of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs; low, medium, and high). There was a modest sacrifice in accuracy using 0.5 as opposed to 1.0 ml. However, the within-batch coefficients of variation, a measure of laboratory error, were consistently low when 0.5-ml aliquots were used. For both DDE and PCB concentrations, this error was less than 5% for the medium and high pools [5-20 parts per billion (ng/ml)] and less than 9% for the low pool (< 1 part per billion). After determining that aliquots of 0.5 ml were sufficient, we performed a blinded quality control analysis of stored plasma. In this study, the within-subject variation was low for DDE and PCBs and substantially lower than the between-subject variation, suggesting that the assay would rank subjects with reasonable precision. Our results suggest that use of 0.5-ml as opposed to 1.0-ml aliquots should not compromise the power of a nested case-control study to detect differences between subjects and would thus save plasma for future research. For populations with very low levels of organochlorines, however, the larger volumes should still be used.

Blood Specimen Collection↗

Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.

A common deletion polymorphism in the gene coding for the glutathione S-transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify carcinogenic epoxide intermediates and has been associated with increased breast cancer risk in some small studies. We studied the GSTM1 gene deletion polymorphism (conferring the null genotype) in 243 women who had prevalent breast cancer and 245 women without breast cancer, who were among the 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent case series, the null genotype was slightly more common among cases (58%) than among controls (51%; age-adjusted odds ratio = 1.30; 95% confidence interval, 0.91-1.86). Among cases, the prevalence of the GSTM1 deletion increased with duration of survival [68% for > or = 8 years since diagnosis; 57% for 4-8 years; 51% for < 4 years; P (trend) = 0.04]. In an incident case series of 240 women who were diagnosed with breast cancer following blood collection and prior to June of 1992 and compared with age-matched controls, the GSTM1 deletion was not associated with an elevation in risk (relative risk, 1.08; 95% confidence interval, 0.74-1.57). No significant interaction with cigarette smoking was evident. Thus, there was no significant increase in risk of incident breast cancer associated with the GSTM1 null genotype; however, the gene deletion polymorphism appeared to confer improved survival. These data suggest that odds ratios based upon prevalent cases in molecular epidemiologic studies may be biased due to differential survival. Further studies are required to determine whether this polymorphism is associated with improved breast cancer prognosis.

Adult↗

Methodological issues in the use of biological markers in cancer epidemiology: cohort studies.

In this chapter we summarize the major strengths and weaknesses of cohort studies; consider how these characteristics influence the use of biomarkers in cohort studies; briefly review considerations of statistical power, design and the influence of measurement error in cohort studies; and discuss some of the emerging ethical considerations that relate to the use of biomarkers in prospective studies.

Biomarkers, Tumor↗

Evaluation of a food frequency questionnaire-food composition approach for estimating dietary intake of inorganic arsenic and methylmercury.

Inorganic arsenic intake in 969 men and women and methylmercury intake in 785 men and women from across the United States were assessed by a semiquantitative food frequency questionnaire, in combination with a database for the content of those elements in foods, and by toenail concentrations of arsenic and mercury. In addition, empirical weights for foods on the dietary questionnaire were derived from multivariate regression models to estimate associations between diet and toenail arsenic and mercury levels, independent of the assumptions about inorganic arsenic and methylmercury in foods, which are based upon limited residue measurements. The use of empirical weights significantly improved the correlation of arsenic consumption with toenail arsenic levels (r = 0.33, P = 0.0001), compared with the weak correlation obtained using the food residue method to calculate intake (r = 0.15, P = 0.0001). Mercury consumption computed using empirical weights yielded a significant correlation with toenail arsenic (r = 0.42, P = 0.001), similar to the correlation using energy-adjusted intake calculated from food residue tables (r = 0.35, P = 0.001). These results illustrate the potential use of empirically derived weights for foods in estimating toenail levels of selected heavy metals and support the validity of published food residue data that are used to estimate mercury consumption.

Adult↗

Birthweight as a risk factor for breast cancer.

BACKGROUND: The mammary gland is largely undifferentiated before birth and may be particularly susceptible to intrauterine influences that could increase the risk of cancer through acceleration of cell proliferation or other pregnancy-related processes. Studies of migrant populations, animal data, and limited epidemiological evidence suggest that breast cancer may originate in utero. In a nested case-control study we assessed whether birthweight and other perinatal factors are associated with risk of breast cancer. METHODS: This case-control study was nested within the cohorts of the two Nurses' Health Studies. We used self-administered questionnaires to obtain information from the mothers of 582 nurses with invasive breast cancer and the mothers of 1569 nurses who did not have breast cancer (controls). Information on risk factors for breast cancer during adulthood were obtained from the nurses; multiple logistic regression analysis adjusted for these risk factors. FINDINGS: Birthweight was a significant predictor of breast-cancer risk. With women who weighed 4000 g or more at birth as the reference category, the adjusted odds ratios for breast cancer were 0.86 (95% CI 0.59-1.25) for birthweights of 3500-3999 g, 0.68 (0.48-0.97) for birthweights of 3000-3499 g, 0.66 (0.45-0.98) for birthweights of 2500-2999 g, and 0.55 (0.33-0.93) for birthweights below 2500 g (p for trend 0.004). Prematurity was not significantly associated with risk of breast cancer. INTERPRETATION: Birthweight is significantly associated with breast-cancer risk, which suggests that intrauterine factors or processes affect the risk of breast cancer in the offspring. High concentrations of pregnancy oestrogens may have an important role in breast carcinogenesis, but other pregnancy hormones or intrauterine factors may also be involved.

Adult↗

A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer.

We examined the relationship of a common polymorphism (667C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene with the risk of colorectal cancer in a case-control study conducted in the Health Professionals Follow-up Study. MTHFR genotypes were ascertained from blood samples among 144 men previously diagnosed with colorectal cancer and 627 controls. The adjusted odds ratio (OR) for the MTHFR variant homozygous (val/val) genotype was 0.57 [95% confidence interval (CI), 0.30-1.06]. High dietary intake of methionine (OR, 0.27; 95% CI, 0.06-1.20) and low consumption of alcohol (OR, 0.11; 95% CI, 0.01-0.85) were associated with reduced incidence of colorectal cancer. Alcohol intake was a stronger risk factor among men with the val/val genotype (P, trend = 0.01), and consumption of five or more alcoholic drinks per week abolished the reduced risk of colorectal cancer among val/val individuals (P, interaction = 0.02). The inverse association of methionine with colorectal cancer risk was slightly stronger among individuals with the MTHFR val/val genotype. These data suggest that dietary methyl supply is particularly critical among MTHFR val/val individuals. When dietary methyl supply is high, MTHFR val/val individuals may be at reduced risk of colorectal cancer probably because higher levels of 5,10-methylenetetrahydrofolate may prevent imbalances of nucleotide pools during DNA synthesis. In contrast, when 5-methyltetrahydrofolate is depleted by alcohol consumption, val/val individuals may be less able to compensate, leading to potentially oncogenic alterations in DNA methylation.

Adult↗

A prospective study of cigarette smoking and the risk of pancreatic cancer.

OBJECTIVES: To prospectively examine the excess incidence of pancreatic cancer among cigarette smokers and to examine the influence of smoking cessation on the risk of pancreatic cancer. METHODS: We obtained data on cigarette smoking and other risk factors for pancreatic cancer from 118,339 women aged 30 to 55 years and 49,428 men aged 40 to 75 years who were without diagnosed cancer. During the 2,116,229 persons-years of follow-up, pancreatic cancer was diagnosed in 186 participants. RESULTS: The multivariate relative risk of pancreatic cancer for current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant, positive trend in risk with increasing pack-years of smoking was observed (P for trend = .004), although this association was confined to cigarette consumption within the past 15 years. Compared with participants who continued to smoke, former smokers had a 48% reduction in pancreatic cancer risk within 2 years of quitting. Ultimately, the relative risk of pancreatic cancer among former smokers approached that for never smokers after less than 10 years of smoking cessation. Overall, the proportion of pancreatic cancers attributable to cigarette smoking was 25%. CONCLUSIONS: Cigarette smoking is associated with an increased risk of pancreatic cancer. The rapid reduction in risk associated with quitting suggests that smoking cessation could eliminate 25% of the 27,000 deaths from pancreatic cancer occurring annually in the United States.

Adult↗

Calcium, vitamin D, and the occurrence of colorectal cancer among women.

BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.

Adult↗

Toenail trace element levels and breast cancer: a prospective study.

The associations between toenail levels of five trace elements and breast cancer risk were studied among a cohort of 62,641 US women who provided toenail clippings and were free from diagnosed breast cancer in 1982. Among 433 cases of breast cancer identified during 4 years of follow-up and their matched controls, the odds ratios comparing the highest with the lowest quintiles and adjusted for established breast cancer risk factors were as follows: for arsenic, 1.12 (95% confidence interval (CI) 0.66-1.91); for copper, 0.91 (95% CI 0.59-1.42); for chromium, 0.96 (95% CI 0.61-1.52); for iron, 0.89 (95% CI 0.56-1.40); and for zinc, 1.09 (95% CI 0.70-1.70). Among postmenopausal women, a marginally significant positive association was observed between toenail chromium levels and breast cancer risk (odds ratio = 1.71, 95% CI 0.87-3.35) (p for trend = 0.07). However, the association between chromium and breast cancer risk was inverse among premenopausal women. Although data on the validity of toenail levels of certain of these elements are limited, these results do not provide evidence for an important effect of arsenic, copper, chromium, iron, or zinc on breast cancer risk.

Adult↗

Prospective study of oral contraceptives and hypertension among women in the United States.

BACKGROUND: Oral contraceptives induce hypertension in approximately 5% of users of high-dose pills that contain at least 50 micrograms estrogen and 1 to 4 mg progestin, and small increases in blood pressure have been reported even among users of modern low-dose formulations. However, neither the responsible hormone in the oral contraceptive nor particular subgroups of women who might be susceptible to the hypertensive effect of oral contraceptives have been identified. METHODS AND RESULTS: In a prospective cohort study in the United States, 68 297 female nurses aged 25 to 42 years and free of diagnosed hypertension, diabetes, coronary heart disease, stroke, and cancer at baseline were followed up for 4 years. During 231 006 person-years of follow-up, 1567 incident cases of hypertension were diagnosed. Compared with women who had never used oral contraceptives, the age-adjusted relative risk was 1.5 (95% CI = 1.2 to 1.8) for current use and 1.1 (95% CI = 0.9 to 1.2) for past use. After adjustment for age, body mass index, hormones cigarette smoking, family history of hypertension, parity, physical activity, alcohol intake, and ethnicity, current users of oral contraceptives had an increased risk of development of hypertension (RR = 1.8; 95% CI = 1.5 to 2.3) compared with women who had never used them. The multivariate relative risk for past users was 1.2 (95% CI = 1.0 to 1.4). There were no important modifying effects of age, family history of hypertension, ethnicity, or body mass index. CONCLUSIONS: Current users of oral contraceptives had a significant, moderately increased risk of hypertension. However, among this group, only 41.5 cases per 10 000 person-years could be attributed to oral contraceptive use. Risk decreased quickly with cessation of oral contraceptives, and past users appeared to have only a slightly increased risk.

Adult↗

Prospective assessment of breastfeeding and breast cancer incidence among 89,887 women.

BACKGROUND: The relation between breastfeeding and breast cancer risk has been examined in many studies; some have reported no association, and others a reduced risk, particularly among premenopausal women. In the only prospective cohort study, no association was found. We have assessed prospectively the association between breastfeeding and incidence of breast cancer among 89,887 women in the US Nurses' Health Study. METHODS: In 1986, participants were asked about the number of months they breastfed for all their children combined. Parous women with no history of cancer were included in this analysis. During 6 years of follow-up (513,015 person-years), 1,459 invasive breast cancer cases were diagnosed. FINDINGS: Relative to women who had never breastfed, no significant overall association was found--after adjusting for established risk factors for breast cancer--between a history of having breastfed and subsequent development of breast cancer (relative risk [RR] 0.93, 95% CI 0.83 -1.03). No inverse trend was observed with duration of breastfeeding; women who breastfed for 2 years of longer had a RR of 1.11 (0.90-1.38). Among women who had given birth only once, women who had breastfed their child experienced a lower incidence of breast cancer (RR 0.68, 0.46-1.00). Among premenopausal women, who tended to be near menopause due to the age structure of the cohort, the RR of breast cancer for those who had lactated was 1.16 (0.89-1.50). Premenopausal women who had lactated for 1 year or more had a RR of 1.10 (0.78-1.57). INTERPRETATION: These data suggest that there is no important overall association between breast-feeding and the occurrence of breast cancer.

Adult↗

Cohort studies of fat intake and the risk of breast cancer--a pooled analysis.

BACKGROUND: Experiments in animals, international correlation comparisons, and case-control studies support an association between dietary fat intake and the incidence of breast cancer. Most cohort studies do not corroborate the association, but they have been criticized for involving small numbers of cases, homogeneous fat intake, and measurement errors in estimates of fat intake. METHODS: We identified seven prospective studies in four countries that met specific criteria and analyzed the primary data in a standardized manner. Pooled estimates of the relation of fat intake to the risk of breast cancer were calculated, and data from study-specific validation studies were used to adjust the results for measurement error. RESULTS: Information about 4980 cases from studies including 337,819 women was available. When women in the highest quintile of energy-adjusted total fat intake were compared with women in the lowest quintile, the multivariate pooled relative risk of breast cancer was 1.05 (95 percent confidence interval, 0.94 to 1.16). Relative risks for saturated, monounsaturated, and polyunsaturated fat and for cholesterol, considered individually, were also close to unity. There was little overall association between the percentage of energy intake from fat and the risk of breast cancer, even among women whose energy intake from fat was less than 20 percent. Correcting for error in the measurement of nutrient intake did not materially alter these findings. CONCLUSIONS: We found no evidence of a positive association between total dietary fat intake and the risk of breast cancer. There was no reduction in risk even among women whose energy intake from fat was less than 20 percent of total energy intake. In the context of the Western lifestyle, lowering the total intake of fat in midlife is unlikely to reduce the risk of breast cancer substantially.

Adult↗

Hair dye use and the risk of developing systemic lupus erythematosus.

OBJECTIVE: To investigate the role of hair dye use in the etiology of systemic lupus erythematosus (SLE). METHODS: Participants included 106,391 women enrolled in the Nurses' Health Study, a prospective cohort study. The subjects were ages 30-55 years in 1976, and were free from SLE and any other connective tissue disease at the time of enrollment. In 1976, 1978, 1980, and 1982, subjects were classified as never-users or ever-users of permanent hair dye, based on self-report. Incidence rates of SLE meeting American College of Rheumatology classification criteria were ascertained and confirmed by chart review. RESULTS: Compared with never-users of permanent hair dye, the age-adjusted relative risks (RR) for the development of SLE among ever-users (n = 85 cases) was 0.96 (95% confidence interval [95% CI] 0.63-1.47). Duration of hair dye use was not related to risk of SLE. Women with 15 or more years of use had no increased risk (RR = 0.92, 95% CI 0.46-1.83). There was no relationship between frequency of use or time since first use and risk of SLE. The results were similar when less stringent criteria for SLE were used. CONCLUSION: We found no evidence that permanent hair dye use, age at first use, frequency of use, or duration of use is associated with the development of SLE.

Adult↗

Nutrition and breast cancer.

Epidemiologic evidence on the relation between nutrition and breast cancer is reviewed. After several decades of study, many aspects of the role of diet in breast cancer etiology are still unclear. Results from large prospective studies do not support the concept developed from animal and ecologic evidence that dietary fat intake in mid-life is associated with breast cancer risk. Thus, if fat intake is relevant to breast cancer, it is probably only at extremely low fat intakes or during early life. An emerging hypothesis that higher energy intake and growth rate in childhood and adolescence increases risk deserves further study. The possibility that diets rich in olive oil may be protective is also intriguing. Considerable evidence suggests that low intake of vegetables modestly increases the risk of breast cancer; however, the nutrients responsible remain elusive. The positive relation of alcohol intake with breast cancer risk has been seen repeatedly, and recently has been buttressed by studies showing that moderate alcohol intake increases estrogen endogenous levels. Advice to increase vegetable intake and limit alcohol consumption would probably have a modest, at best, effect on breast cancer risk. Future studies of the relation of nutrition during early life to subsequent breast cancer risk are needed.

Adolescent↗

The changing roles of health care personnel in health and health care management.

Health care reform has become a global phenomenon. Countries are experiencing similar problems with their health care systems and are reaching for similar solutions. Management is seen as crucial in many countries as the principal means of securing supply-side reforms. Many of these centre on establishing a new relationship between professionals, notably the medical profession, and the state. The aim has been to exercise greater influence over how professionals practice and use resources. The application of new public management principles based on industrial sector practices and concepts of management has created tensions within professional groups who feel themselves, and their craft, to be under attack. But the new managerialism has to be seen within a context of rapid social and economic change. It is not possible to predict what the impact of such change is likely to be on health services in the future or on those who provide them. The paper offers an overview of health care reforms and assesses how it is shaping, or re-shaping, the roles and tasks of health care personnel. One conclusion is the mismatch between the management style favoured by policy-makers and reformers and the necessary flexibility required in skill mix and organization of work. High-trust relations lie at the heart of professional forms of organisation whereas the new managerialism appears to be based on the expectation of low-trust relations. The paper concludes with a brief look at the implications of all these developments for training and education and finds that there is still a long way to go before there is any real prospect of providing and equipping health care personnel with the requisite skills to enable them to meet the complex challenges that are a common characteristic of health care systems.

Delivery of Health Care↗

The lack of association of marijuana and other recreational drugs with progression to AIDS in the San Francisco Men's Health Study.

We evaluated the associations of specific recreational drugs and alcohol with laboratory predictors of AIDS at entry into the San Francisco Men's Health Study (SFMHS) in 1984 and with the development of the acquired immunodeficiency syndrome (AIDS) during 6 years of follow-up. Marijuana use was associated with a decreased rate of progression to AIDS in the univariate analysis (RR = 0.7; P = 0.01). Marijuana use was more common among individuals with elevated HIV viral core protein antibody (p24Ab) titer (> 1:16) at baseline (P = 0.03); this finding suggests that marijuana users were healthier at baseline. When the data were adjusted for p24 Ab and other laboratory parameters, no association with progression to AIDS was observed for marijuana, suggesting that the observed univariate result was due to a difference in HIV-related disease at the time of enrollment. No statistically significant associations were observed for nitrites, methylene dioxyamphetamines, ethyl chloride, downers, cocaine, stimulants, narcotics, or psychedelic drugs. These data suggest no substantial association between use of these drugs and the development of AIDS among HIV-infected men.

Acquired Immunodeficiency Syndrome↗