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D J Hunter

Publications and source records attributed to D J Hunter.

At least 73 records · Page 4Linked to original sources
PubMed2000

Polymorphic repeat in AIB1 does not alter breast cancer risk.

STATEMENT OF FINDINGS: We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population.

Adult↗
PubMed2000

Prospective study of talc use and ovarian cancer.

BACKGROUND: Perineal talc use has been associated with an increased risk of ovarian cancer in a number of case-control studies; however, this association remains controversial because of limited supporting biologic evidence and the potential for recall bias or selection bias in case-control studies. In this study, we conducted a prospective analysis of perineal talc use and the risk of ovarian cancer. METHODS: The Nurses' Health Study is a prospective study of 121 700 female registered nurses in the United States who were aged 30-55 years at enrollment in 1976. Talc use was ascertained in 1982 by use of a self-administered questionnaire: after exclusions, 78 630 women formed the cohort for analysis. Three hundred seven epithelial ovarian cancers subsequently diagnosed in this cohort through June 1, 1996, were confirmed by medical record review and met inclusion criteria. Proportional hazards models by use of pooled logistic regression were used to derive relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: In 1982, 40.4% (n = 31 789) of the cohort reported ever using talc, and 14.5% (n = 11 411) reported ever using talc daily. We observed no overall association with ever talc use and epithelial ovarian cancer (multivariate RR = 1.09; 95% CI = 0.86-1.37) and no increase in risk of ovarian cancer with increasing frequency of use. There was a modest elevation in risk for ever talc use and invasive serous ovarian cancer (multivariate RR = 1.40; 95% CI = 1.02-1.91). The risk of epithelial ovarian cancer for talc users was not greater among women who had never had a tubal ligation (multivariate RR = 0.97; 95% CI = 0.71-1.32). CONCLUSION: Our results provide little support for any substantial association between perineal talc use and ovarian cancer risk overall; however, perineal talc use may modestly increase the risk of invasive serous ovarian cancer.

Adult↗
PubMed2000

Angular dependences of perpendicular and parallel mode electron paramagnetic resonance of oxidized beef heart cytochrome c oxidase.

Cytochrome c oxidase catalyzes the reduction of oxygen to water with a concomitant conservation of energy in the form of a transmembrane proton gradient. The enzyme has a catalytic site consisting of a binuclear center of a copper ion and a heme group. The spectroscopic parameters of this center are unusual. The origin of broad electron paramagnetic resonance (EPR) signals in the oxidized state at rather low resonant field, the so-called g' = 12 signal, has been a matter of debate for over 30 years. We have studied the angular dependence of this resonance in both parallel and perpendicular mode X-band EPR in oriented multilayers containing cytochrome c oxidase to resolve the assignment. The "slow" form and compounds formed by the addition of formate and fluoride to the oxidized enzyme display these resonances, which result from transitions between states of an integer-spin multiplet arising from magnetic exchange coupling between the five unpaired electrons of high spin Fe(III) heme a(3) and the single unpaired electron of Cu(B). The first successful simulation of similar signals observed in both perpendicular and parallel mode X-band EPR spectra in frozen aqueous solution of the fluoride compound of the closely related enzyme, quinol oxidase or cytochrome bo(3), has been reported recently (Oganesyan et al., 1998, J. Am. Chem. Soc. 120:4232-4233). This suggested that the exchange interaction between the two metal ions of the binuclear center is very weak (|J| approximately 1 cm(-1)), with the axial zero-field splitting (D approximately 5 cm(-1)) of the high-spin heme dominating the form of the ground state. We show that this model accounts well for the angular dependences of the X-band EPR spectra in both perpendicular and parallel modes of oriented multilayers of cytochrome c oxidase derivatives and that the experimental results are inconsistent with earlier schemes that use exchange coupling parameters of several hundred wavenumbers.

Animals↗
PubMed2000

Harvard report on cancer prevention volume 4: Harvard Cancer Risk Index. Risk Index Working Group, Harvard Center for Cancer Prevention.

OBJECTIVE: Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States. METHODS: We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data. RESULTS: The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer. CONCLUSION: The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages.

Adult↗
PubMed2000

Diet and basal cell carcinoma of the skin in a prospective cohort of men.

BACKGROUND: Low intake of fat and high intake of specific vitamins have been hypothesized to reduce risk of basal cell carcinoma of the skin (BCC). OBJECTIVE: Our objective was to examine intakes of fat, antioxidant nutrients, retinol, folate, and vitamin D in relation to risk of BCC. DESIGN: In 1986, diet was assessed by a validated food-frequency questionnaire in 43217 male participants of the Health Professionals Follow-up Study who were 40-75 y of age and free of cancer. During 8 y of follow-up, we ascertained 3190 newly diagnosed cases of BCC. RESULTS: Total fat consumption was associated with a lower risk of BCC [relative risk (RR): 0.81; 95% CI: 0.72, 0.90 for the highest compared with the lowest quintile of intake; P for trend < 0.001). Simultaneous modeling of specific fatty acids suggested that this inverse association was limited to monounsaturated fat (RR: 0.79; 95% CI: 0.65, 0.96; P for trend = 0. 02); saturated and polyunsaturated fat were not associated with BCC risk. Folate intake was associated with a slightly higher risk of BCC (RR: 1.19; 95% CI: 1.01, 1.40; P for trend = 0.11), whereas alpha-carotene was associated with a slightly lower risk (RR: 0.88; 95% CI: 0.79, 0.99; P for trend = 0.01). Intakes of long-chain n-3 fatty acids, retinol, vitamin C, vitamin D, or vitamin E were not materially related to BCC risk. CONCLUSIONS: These findings do not support the hypothesis that diets low in fat or high in specific vitamins lower risk of BCC.

Adult↗
PubMed2000

Adherence to the Dietary Guidelines for Americans and risk of major chronic disease in women.

BACKGROUND: Little is known about the overall health effects of adherence to the Dietary Guidelines for Americans. The healthy eating index (HEI), developed at the US Department of Agriculture, measures how well Americans' diets conform to these guidelines. OBJECTIVE: We tested whether the HEI (scores range from 0 to 100; 100 is best) calculated from food-frequency questionnaires (HEI-f) would predict risk of major chronic disease in women. DESIGN: A total of 67272 US female nurses who were free of major disease completed detailed questionnaires on diet and chronic disease risk factors in 1984 and repeatedly over 12 y. Major chronic disease was defined as fatal or nonfatal cardiovascular disease (myocardial infarction or stroke, n = 1365), fatal or nonfatal cancer (n = 5216), or other nontraumatic deaths (n = 496), whichever came first. We also examined cardiovascular disease and cancer as separate outcomes. RESULTS: After adjustment for smoking and other risk factors, the HEI-f score was not associated with risk of overall major chronic disease in women [relative risk (RR) = 0.97; 95% CI: 0.89, 1.06 comparing the highest with the lowest quintile of HEI-f score]. Being in the highest HEI-f quintile was associated with a 14% reduction in cardiovascular disease risk (RR = 0.86; 95% CI: 0.72, 1. 03) and was not associated with lower cancer risk (RR = 1.02; 95% CI: 0.93, 1.12). CONCLUSION: These data suggest that adherence to the 1995 Dietary Guidelines for Americans, as measured by the HEI-f, will have limited benefit in preventing major chronic disease in women.

Adult↗
PubMed2000

Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania.

The objective of this cross-sectional study was to identify risk factors for anemia among human immunodeficiency virus (HIV)-positive pregnant women in Dar es Salaam, Tanzania. Baseline data from 1064 women enrolled in a clinical trial on the effect of vitamin supplementation in HIV infection were examined to identify potential determinants of anemia. The mean hemoglobin (Hb) level was 94 g/L, and the prevalence of severe anemia (Hb < 85 g/L) was 28%; 83% of the women had Hb < 110 g/L. Iron deficiency and infectious disease appeared to be the predominant causes of anemia. Significant independent associations with severe anemia were observed for women with body mass index (BMI) < 19 kg/m(2) compared with women with BMI > 24 kg/m(2) [odds ratio (OR) 3.13, 95% confidence interval (CI): 1. 37-7.14); malaria parasite densities > 1000/mm(3) (OR 2.70, CI: 1. 58-4.61) compared with women with no parasites; eating soil during early pregnancy (OR 2.47, CI: 1.66-3.69); CD4+ cell count < 200/microL compared with CD4+ count > 500/microL (OR 2.70, CI: 1. 42-5.12); and serum retinol levels < 70 micromol/L (OR 2.45, CI: 1. 44-4.17) compared with women with retinol levels > 1.05 micromol/L. The most significant risk factors associated with severe anemia in this population are preventable. Public health recommendations include increasing the effectiveness of iron supplementation and malaria management during pregnancy, and providing health education messages that increase awareness of the potentially adverse nutritional consequences of eating soil during pregnancy.

Adult↗
PubMed2000

NHS reforms in the United Kingdom and learning from developing country experience.

The NHS has been the object of much international interest from its inception and through its periodic reforms. However, UK policy-makers have expressed only limited and selective concern for health sector reforms in other countries. This paper seeks to identify key elements of the present process and content of reforms to the UK NHS and examine the extent to which international learning would be important in developing these reforms. Particular emphasis is placed on learning from developing country experience. The paper therefore considers the policy process in the UK, the focus on primary care, the shift from competitive to collaborative strategies in addition to prioritising and planning. Each is considered in relation to developing country experience and the opportunities for learning. The paper concludes by setting out four areas leading to an international opening in NHS policy processes: developing political space in policy making, developing mechanisms for international exchanges, understanding policy context, and broadening international experience and changing values. The notion of a one-way process in international policy learning is rejected: while the South can learn from the North, so too can the North from the South.

Cooperative Behavior↗
PubMed2000

Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers.

Germline mutations in PTEN can predispose people to Cowden syndrome (CS) and Bannayan-Ruvalcaba-Riley (BRR) syndrome, rare, autosomal dominantly inherited neoplastic disorders. To determine whether germline mutations in PTEN contribute to genetic predisposition to multiple primary tumours within the general population, we conducted a nested case-control study, among 32 826 members of the prospective Nurses' Health Study cohort; cases were women with more than one primary tumour at different anatomical sites. We screened all nine exons of PTEN and flanking intronic splice sites for all 103 eligible cases using SSCP and sequencing. We observed two novel germline heterozygous missense mutations in exon 5 in five of the cases; three were V119L and two were V158L. Neither mutation was observed in 115 controls free of diagnosed cancer (p = 0.02). Both mutants showed partial tumour suppressor activity when compared to wild type PTEN when transfected into a PTEN null breast cancer cell line. The phenotype was cell line specific suggesting that genetic background affects growth suppression activity of the mutants. These data provide evidence that germline mutations in PTEN may be a more frequent predisposing factor for cancers in women than previously suggested.

Breast Neoplasms↗
PubMed2000

Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin's lymphoma among women.

Non-Hodgkin's lymphoma is etiologically related to suppressed immune status, and certain nutrients found in fruits and vegetables have been associated with increased immune responses. However, limited information exists on associations between intake of fruits, vegetables, and related nutrients and non-Hodgkin's lymphoma risk. We thus examined these associations among 88,410 women in the Nurses' Health Study cohort who were aged 34-60 years in 1980 and provided dietary information in 1980. During 14 years of follow-up, we documented 199 incident cases of non-Hodgkin's lymphoma. Higher intake of fruits and vegetables was associated with a lower risk of non-Hodgkin's lymphoma (P for trend = 0.02); the multivariate relative risk (RR) was 0.62 [95% confidence interval (CI), 0.38-1.02] for women who consumed greater than or equal to six servings per day as compared with those consuming less than three servings per day. When fruits and vegetables were examined separately, intake of vegetables rather than fruits was most clearly associated with a reduced risk (P for trend = 0.02 for vegetables; P for trend = 0.16 for fruits); compared with those consuming less than one serving per day, the multivariate RRs were 0.62 (95% CI, 0.35-1.07) for women who consumed greater than or equal to three servings per day of vegetables and 0.70 (95% CI, 0.44-1.12) for women who consumed this amount of fruits. Higher intake of cruciferous vegetables was also associated with a decreased risk (P for trend = 0.03); the multivariate RR was 0.67 (95% CI, 0.40-1.11) for women who consumed greater than or equal to five servings per week as compared with those consuming less than two servings per week. These associations were slightly attenuated when we additionally adjusted for intake of beef, pork, or lamb as a main dish. Intake of dietary fiber from vegetable sources was related to a reduced risk; the multivariate RR was 0.54 (95% CI, 0.34-0.87) for women in the highest quintile as compared with those in the lowest quintile (P for trend = 0.01), and it was slightly attenuated with additional adjustment for saturated and trans unsaturated fats. However, we observed no associations between intakes of specific dietary carotenoids, vitamins A, C, E, and folate, and non-Hodgkin's lymphoma risk. Higher intake of vegetables, particularly cruciferous vegetables, may reduce the risk of non-Hodgkin's lymphoma among women.

Adult↗
PubMed2000

Risk factors for HIV-1 seroprevalence among family planning clients in Dar es Salaam, Tanzania.

Between March and September of 1995, women receiving family planning (FP) services in three large clinics in Dar es Salaam, Tanzania were invited to participate in a cross-sectional study. Consenting women were interviewed to obtain information about HIV risk factors, and blood for HIV testing was collected. The prevalence of HIV was 16.9% (95% CI: 14.4%-19.3%). The risk of HIV increased significantly with age. Compared with married women, the risk of HIV was significantly higher among cohabiting women (age-adjusted OR = 2.3; 95% CI = 1.5-3.5) and among women who were single, divorced or widowed (age-adjusted OR = 2.3; 95% CI = 1.2-4.4). The risk of HIV was also significantly higher among hotel workers (age-adjusted OR = 4.3; 95% CI = 1.4-12.9). Women with laboratory evidence of sexually transmitted diseases were at increased risk of HIV. This study shows that HIV is a major public health problem among FP clients in Tanzania. Innovative HIV interventions are needed to reduce further spread of HIV infection.

Adolescent↗
PubMed2000

Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and adenomatous polyps of the distal colorectum.

1,25-dihydroxyvitamin D [1,25(OH)2D] inhibits proliferation and promotes differentiation of human colon cancer cell lines. Epidemiological findings, although not entirely consistent, suggest an inverse relationship between vitamin D intake and colorectal cancer and adenoma, colorectal cancer precursor lesions. We evaluated the relationship of plasma 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] with distal colorectal adenoma among 326 matched case and control pairs (nested in the prospective Nurses' Health Study), who provided blood in 1989-1990 and who underwent endoscopy in 1989-1996. Plasma vitamin D metabolite concentrations were determined blindly by RIA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple conditional logistic regression models. Mean plasma 1,25(OH)2D and 25(OH)D levels did not significantly differ (P = 0.3 and 0.7, respectively) between cases (31.6 +/- 8.4 pg/ml and 26.4 +/- 10.6 ng/ml, respectively) and controls (32.2 +/- 8.6 pg/ml and 26.8 +/-10.2 ng/ml, respectively). However, women whose plasma 1,25(OH)2D concentration was below 26.0 pg/ml (a level typically considered to be below normal) were at increased risk of distal colorectal adenoma (OR, 1.58; 95% CI, 1.03-2.40). Compared with the lowest 1,25(OH)2D quartile, women in the second (OR, 0.64; 95% CI, 0.41-1.02), third (OR, 0.80; 95% CI, 0.50-1.30), or upper (OR, 0.71; 95% CI, 0.43-1.15) quartiles were at a statistically nonsignificant lower risk of adenoma. The relationship was stronger for large/villous adenoma and among those with consistent vitamin D intake over the 10 years prior to blood draw. Compared with women in the lowest quartile, for plasma 25(OH)D, women in the second (OR, 0.64; 95% CI, 0.41-1.00) and third (OR, 0.58; 95% CI, 0.36-0.95) quartiles were at a statistically significantly lower risk of distal colorectal adenoma, but there was no difference in risk in the top quartile (OR, 1.04; 95% CI, 0.66-1.66). We conclude that women who have low levels of circulating 1,25(OH)2D may be at higher risk of distal colorectal adenomas, but additional study is warranted.

Adenoma↗
PubMed2000

A prospective study of the effect of alcohol consumption and ADH3 genotype on plasma steroid hormone levels and breast cancer risk.

One suggested mechanism underlying the positive association between alcohol consumption and breast cancer risk is an influence of alcohol on steroid hormone levels. A polymorphism in alcohol dehydrogenase type 3 (ADH3) affects the kinetics of alcohol oxidation and thereby could influence the effect of alcohol consumption on hormone levels. We investigated the ADH3 polymorphism, alcohol intake, and risk of breast cancer in a nested case-control study. Among women in the Nurses' Health Study who gave a blood sample in 1989-1990, 465 incident breast cancer cases were diagnosed before June 1994 and were matched to 621 controls. Using conditional logistic regression, we calculated relative risks and confidence intervals to assess breast cancer risk for ADH3 genotype. Among postmenopausal controls not using hormones at time of blood collection, partial Pearson correlation coefficients were calculated to assess the association between alcohol intake and plasma hormone levels according to ADH3 genotype. No association was observed between ADH3 genotype and overall breast cancer risk (relative risk = 0.9 for slow oxidizers compared with fast; 95% confidence interval = 0.6-1.3). Among postmenopausal women, ADH3 genotype did not modify the weak association observed between alcohol intake and breast cancer risk (P for interaction = 0.45). Statistically significant trends in the relationship between alcohol consumption and hormone level dependent on oxidative capacity (ADH3 genotype) were observed for dehydroepiandrosterone sulfate and sex hormone-binding globulin (P < 0.05). These data suggest that the ADH3 polymorphism modestly influences the response of some plasma hormones to alcohol consumption but is not independently associated with breast cancer risk and does not modify the association between alcohol and breast cancer risk.

Adult↗
PubMed1999

Waist circumference, waist:hip ratio, and risk of breast cancer in the Nurses' Health Study.

This study examined prospectively the associations of waist circumference and waist:hip circumference ratio with risk of breast cancer. A total of 47,382 US registered nurses who reported their waist and hip circumferences in 1986 were followed up through May 1994 for identification of incident cases of breast cancer. During 333,097 person-years of follow-up, 1,037 invasive breast cancers were diagnosed. In proportional hazards analyses, waist circumference was nonsignificantly related to risk of premenopausal breast cancer but was significantly associated with postmenopausal breast cancer after adjustment for established breast cancer risk factors (for the highest quintile of waist circumference vs. the lowest, relative risk (RR) = 1.34; 95% confidence interval (CI): 1.05, 1.72). When the analysis was limited to postmenopausal women who had never received hormone replacement therapy, a stronger positive association was found (RR = 1.88; 95% CI: 1.25, 2.85). After the data were further controlled for body mass index, the positive association was only slightly attenuated (RR = 1.83; 95% CI: 1.12, 2.99). Among past and current postmenopausal hormone users, no significant associations were found. Similar but slightly weaker associations were observed between waist:hip ratio and breast cancer risk. These data suggest that greater waist circumference increases risk of breast cancer, especially among postmenopausal women who are otherwise at lower risk because of never having used estrogen replacement hormones.

Abdomen↗
PubMed1999

Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility.

BACKGROUND: The enzymes encoded by the glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactivation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may also be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk. METHODS: Our study included 466 women with incident cases of breast cancer occurring from May 1989 through May 1994 and 466 matched control subjects. These individuals were part of a prospective cohort of U.S. women (i.e., the Nurses' Health Study). Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression models were used to estimate the association between genetic polymorphisms and breast cancer risk. RESULTS: The GSTM1 and GSTT1 null genotypes were not associated with an increased risk of breast cancer (OR = 1.05 [95% CI = 0.80-1.37] for GSTM1 null; OR = 0. 86 [95% CI = 0.61-1.21] for GSTT1 null). On the contrary, a suggestion of a decreased risk of breast cancer associated with the GSTT1 null genotype was observed among premenopausal women. When considered together, no combination of the GSTM1 and GSTT1 genotypes was associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was not substantially modified by cigarette smoking. CONCLUSIONS: Our data provide evidence against a substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions.

Breast Neoplasms↗
PubMed1999

A prospective study of recreational physical activity and breast cancer risk.

BACKGROUND: Increased physical activity has been hypothesized to prevent breast cancer, largely by reducing cumulative lifetime exposure to circulating ovarian hormones. However, epidemiologic findings are inconsistent, and there is no consensus on the best way to quantify physical activity. We thus examined this issue in a large cohort of women, using several different measures of adult physical activity. METHODS: We analyzed data from the Nurses' Health Study, a prospective study of women aged 30 to 55 years in 1976. In 1980 and on subsequent surveys, women were asked about the average number of hours per week spent in various moderate and vigorous recreational physical activity during the past year. We computed a "baseline-only" (1980) measure of hours per week of physical activity, as well as a cumulative average measure that used updated reports on physical activity. During 16 years of follow-up, we identified 3137 cases of invasive breast cancer (1036 premenopausal and 2101 postmenopausal women). Data were analyzed by use of multivariate pooled logistic regression to produce relative risks of breast cancer, and the associated confidence intervals. RESULTS: Women who were more physically active in adulthood had a lower risk of breast cancer than those who were less physically active. Comparing those who reported engaging in moderate or vigorous physical activity for 7 or more hours per week with those who engaged in such physical activity for less than 1 hour per week, the relative risk was 0.82 (95% confidence interval, 0.70-0.97), using the cumulative average updating. The dose-response trend was statistically significant (P = .004). Using the baseline-only measure of physical activity produced slightly weaker relative risks. CONCLUSION: These results contribute to the body of evidence suggesting that higher levels of adult physical activity afford modest protection against breast cancer.

Adult↗