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Biomedical subjects

D J Hunter

Publications and source records attributed to D J Hunter.

At least 109 records · Page 6Linked to original sources
PubMed1999

Oral contraceptive use and risk of melanoma in premenopausal women.

Melanoma has been increasing in white populations. Incidence rates rise steeply in women until about age 50, suggesting oestrogen as a possible risk factor. Oestrogens can increase melanocyte count and melanin content and cause hyperpigmentation of the skin. We examined prospectively the association between oral contraceptive (OC) use and diagnoses of superficial spreading and nodular melanoma among 183,693 premenopausal white women in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. One hundred and forty six cases were confirmed in NHS during follow-up from 1976 to 1994, and 106 cases were confirmed in NHS II from 1989 to 1995. Skin reaction to sun exposure, sunburn history, mole counts, hair colour, family history of melanoma, parity, height and body mass index were also assessed and included in logistic regression models. A significant twofold increase in risk of melanoma (relative risk (RR) = 2.0, 95% confidence interval (CI) 1.2-3.4) was observed among current OC users compared to never users. Risk was further increased among current users with 10 or more years of use (RR = 3.4, 95% CI 1.7-7.0). Risk did not appear elevated among past OC users, even among those with longer durations of use, and risk did not decline linearly with time since last use. In conclusion, risk of premenopausal melanoma may be increased among women who are current OC users, particularly among those with longer durations of use. Further research is needed to determine whether low-dose oestrogen pills in particular are associated with an increase in risk and to describe possible interactions between OC use and sun exposure or other risk factors for melanoma.

Adult↗
PubMed1999

MTHFR polymorphism, methyl-replete diets and the risk of colorectal carcinoma and adenoma among U.S. men and women: an example of gene-environment interactions in colorectal tumorigenesis.

Our studies on interactions of a folate-metabolizing gene polymorphism and dietary intake in colorectal tumorigenesis demonstrate the potential importance of studying interactions between genotype and environmental exposure in relation to cancer risk. We observed an inverse association of a polymorphism (667C --> T, ala --> val) in the methylenetetrahydrofolate reductase (MTHFR) gene with colorectal cancer but not with colorectal adenomas. The inverse association of methionine and adverse association of alcohol with colorectal cancer were stronger among val/val individuals. These interactions were not present in studies of colorectal adenomas. Our studies illustrate that studying gene-environment interactions in relation to cancer can be of importance in clarifying cancer etiology as well as pointing to preventive dietary modifications.

Adenoma↗
PubMed1999

Predictors of plasma concentrations of DDE and PCBs in a group of U.S. women.

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age (p = 0.0003), and PCBs increased 0.08 ppb (p = 0.0001). DDE and PCBs increased 0.20 (p = 0.02) and 0.13 ppb (p = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; p = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; p = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs.

Adult↗
PubMed1999

Lead and hypertension in a sample of middle-aged women.

OBJECTIVES: The role of lead exposure as a risk factor for hypertension is less well defined among women than among men. This case-control study assessed the relation of blood and bone lead concentrations to hypertension in women. METHODS: Cases and controls were a subsample of women from the Nurses' Health Study. Hypertension was defined as a physician diagnosis of hypertension between 1988 and 1994 or measured systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg. RESULTS: Mean (SD) blood lead concentration was 0.15 (0.11) mumol/L; mean tibia and patella lead concentrations by K-x-ray fluorescence were 13.3 (9.0) and 17.3 (11.1) micrograms/g, respectively. After adjustment for potentially confounding factors, an increase from the 10th to the 90th percentile of patella lead values (25 micrograms/g) was associated with approximately 2-fold (95% confidence interval = 1.1, 3.2) increased risk of hypertension. There was no association between hypertension and either blood or tibia lead concentrations. CONCLUSIONS: These findings support a potentially important role for low-level lead exposure as a risk factor for hypertension among non-occupationally exposed women.

Body Burden↗
PubMed1999

A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk.

We previously reported (J. Chen et al., Cancer Res., 56: 4862-4864, 1996; J. Ma et al., Cancer Res., 57: 1098-1102, 1997) that a 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism (677C-->T, ala-->val) was associated with lower risk of colorectal cancer. In this study, we examined the relationship of a polymorphism (2756A-->G, asp-->gly) in the gene (MTR) for methionine synthase, another important enzyme in the same folate/methionine/homocyst(e)ine metabolic pathway, with risk of colorectal cancer among 356 cases and 476 cancer-free controls. The frequency of the homozygous variant genotype (gly/gly) was slightly lower among cases (3%) than controls (5%). The odds ratio for the gly/gly genotype was 0.59 [95% confidence interval (CI), 0.27-1.27] compared with those with the homozygous wild type (asp/asp). There were no significant differences in plasma levels of folate, vitamin B12, and homocyst(e)ine (tHcy) among the MTR genotypes, in contrast to the MTHFR polymorphism. However, similar to the interaction observed for the MTHFR polymorphism among men who consumed less than 1 alcoholic drink/day, those with the gly/gly genotype had a lower risk of colorectal cancer with an odds ratio of 0.27 (95% CI, 0.09-0.81) compared with those with the asp/asp genotype. The possible association of the MTR polymorphism with lower risk of colorectal cancer especially among those with low alcohol consumption, in the same direction as for the MTHFR polymorphism, is intriguing. However, our study had limited statistical power because of the low frequency of the MTR variant genotype, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1999

Reproducibility and validity of maternal recall of pregnancy-related events.

We assessed the reproducibility and validity of a questionnaire that asks mothers to recall pregnancy-related events from thirty or more years ago. Among 146 women who completed the questionnaire twice, responses were highly reproducible for pre-pregnancy height and weight (r = 0.95), pregnancy complications (r = 0.74), substance use (r = 0.80), preterm delivery (r = 0.82), birthweight (r = 0.94), and breastfeeding (r = 0.89). Among 154 women whose questionnaire responses were compared to data collected during their pregnancies, recall was highly accurate for height (r = 0.90), pre-pregnancy weight (r = 0.86), birthweight (r = 0.91), and smoking (sensitivity = 0.86, specificity = 0.94). These findings suggest that long-term maternal recall is both reproducible and accurate for many factors related to pregnancy and delivery.

Aged↗
PubMed1999

Association of age and reproductive factors with benign breast tissue composition.

Reproductive breast cancer risk factors are hypothesized to act by increasing exposure of the breast to endogenous estrogens, but few studies have quantitatively examined the association of these risk factors with breast tissue composition. This study is part of a case-control study of breast histological characteristics and breast cancer risk, nested within the Nurses' Health Study, a prospective study of 121,700 registered nurses. We studied 300 women who had not been diagnosed with breast cancer, but for whom we obtained slides from a prior benign breast biopsy. We used a computer-assisted image analysis technique to assess the proportion of epithelial and fibrous stromal tissue on benign breast biopsy slides, excluding obvious mass lesions. Mean epithelial proportion was 5.3% (0.1-23%), and mean stromal proportion was 58.7% (3-93%). Women with proliferative breast disease without atypia had higher epithelial and stromal proportions than women with nonproliferative breast disease (P < 0.001). Postmenopausal women had a lower epithelial proportion (P = 0.01), and increasing age at biopsy was associated with decreasing stromal proportion among postmenopausal parous women (P = 0.004). Among premenopausal women, increasing years since last birth was associated with lower epithelial proportion (P < 0.001). Other reproductive risk factors were not independently associated with epithelial or stromal proportion. Epithelial and stromal breast tissue were associated with different factors with the exception of proliferative breast disease, which was associated with an increase in both epithelial and stromal proportion. The quantitative measurement of epithelial and stromal proportion may be useful for measuring changes in breast composition.

Age Factors↗
PubMed1999

Alcohol consumption in relation to breast cancer risk in a cohort of United States women 25-42 years of age.

We evaluated current and past alcohol consumption prospectively in relation to breast cancer risk among 116,671 women ages 25-42 years old at enrollment in 1989. During 6 years of follow-up, 445 cases of invasive breast cancer were identified. For alcohol consumption in the previous year, the multivariate relative risk associated with more than 20 g/day (approximately 10 drinks/week) was 1.23 (95% confidence interval, 0.68-2.21); the P for trend was 0.85. For average lifetime alcohol consumption, the multivariate relative risk associated with consumption of 10 or more drinks/week was 1.20 (95% confidence interval, 0.69-2.11); the P for trend was 0.18. We examined drinking in several time periods of life; only drinking at ages 23-30 was significantly positively associated with risk. Although this may represent a chance finding, it merits further study. Because drinking levels in this population were low, we had limited information on heavier drinking. Our results suggest that there is unlikely to be a large effect of moderate alcohol consumption on breast cancer risk among young women, although a modest effect cannot be excluded. The association between alcohol consumption and breast cancer is unlikely to be substantially stronger among premenopausal women than among postmenopausal women.

Adolescent↗
PubMed1999

Epidemiology of interstitial cystitis: a population based study.

PURPOSE: Interstitial cystitis is a chronic and debilitating syndrome but surprisingly little is known about its epidemiology. This study was designed to estimate the prevalence of interstitial cystitis among women in the United States. MATERIALS AND METHODS: Female participants in the Nurses' Health Study (NHS) I and II (184,583) were asked by mailed questionnaires whether they had ever been diagnosed with interstitial cystitis. We requested and reviewed medical records of women self-reporting interstitial cystitis. The accuracy of self-reports was evaluated using standardized criteria. RESULTS: Among the 93,428 women who responded to the NHS II questionnaire and 91,155 women who responded to the NHS I questionnaire 1,354 (1.4%) and 357 (0.4%), respectively, self-reported interstitial cystitis. Based on medical record review 63 cases of interstitial cystitis were confirmed in NHS II and 47 in NHS I. The prevalence of interstitial cystitis was 67/100,000 women in NHS II and 52/100,000 in NHS I. There was no substantial variation in prevalence by age. CONCLUSIONS: The prevalence of interstitial cystitis in the United States is more than 50% greater than previously reported and 3-fold greater than that reported in Europe.

Adult↗
PubMed1998

The surface-charge asymmetry and dimerisation of cytochrome c550 from Paracoccus denitrificans--implications for the interaction with cytochrome c peroxidase.

The implications of the dimeric state of cytochrome c550 for its binding to Paracoccus cytochrome c peroxidase and its delivery of the two electrons required to restore the active enzyme during catalysis have been investigated. The amino acid sequence of cytochrome c550 of Paracoccus denitrificans strain LMD 52.44 was determined and showed 21 differences from that of strain LMD 22.21. Based on the X-ray structure of the latter, a structure for the cytochrome c550 monomer from strain 52.44 is proposed and a dipole moment of 945 debye was calculated with an orientation close to the exposed haem edge. The behaviour of the cytochrome on molecular-exclusion chromatography is indicative of an ionic strength-dependent monomer (15 kDa)/dimer (30 kDa) equilibrium that can also be detected by 1H-NMR spectroscopy. The apparent mass of 50 kDa observed at very low ionic strength was consistent with the presence of a strongly asymmetric dimer. This was confirmed by cross-linking studies, which showed that a cross-linked species of mass 30 kDa on SDS behaved with an apparent mass of 50 kDa on molecular-exclusion chromatography. A programme which carried out and evaluated molecular docking of two monomers to give a dimer generated a most probable dimer in which the monomer dipoles lay almost antiparallel to each other. The resultant dipole moment of the dimer is therefore small. Although this finding calls into question the possibility of preorientation of a strongly asymmetrically charged cytochrome as it collides with a redox partner, the stoichiometry of complex formation with cytochrome c peroxidase as studied by 1H-NMR spectroscopy shows that it is the monomer that binds.

Amino Acid Sequence↗
PubMed1998

Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.

BACKGROUND: High intake of folate may reduce risk for colon cancer, but the dosage and duration relations and the impact of dietary compared with supplementary sources are not well understood. OBJECTIVE: To evaluate the relation between folate intake and incidence of colon cancer. DESIGN: Prospective cohort study. SETTING: 88,756 women from the Nurses' Health Study who were free of cancer in 1980 and provided updated assessments of diet, including multivitamin supplement use, from 1980 to 1994. PATIENTS: 442 women with new cases of colon cancer. MEASUREMENTS: Multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake. RESULTS: Higher energy-adjusted folate intake in 1980 was related to a lower risk for colon cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake > 400 microg/d compared with intake < or = 200 microg/d) after controlling for age; family history of colorectal cancer; aspirin use; smoking; body mass; physical activity; and intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A, C, D, and E and intake of calcium were also controlled for, results were similar. Women who used multivitamins containing folic acid had no benefit with respect to colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15 years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]), representing 15 instead of 68 new cases of colon cancer per 10,000 women 55 to 69 years of age. Folate from dietary sources alone was related to a modest reduction in risk for colon cancer, and the benefit of long-term multivitamin use was present across all levels of dietary intakes. CONCLUSIONS: Long-term use of multivitamins may substantially reduce risk for colon cancer. This effect may be related to the folic acid contained in multivitamins.

Adult↗
PubMed1998

Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women.

BACKGROUND: A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study. METHODS: Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11,169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection. RESULTS: From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23-4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy. CONCLUSION: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer.

Adult↗
PubMed1998

Physical activity and breast cancer risk in a cohort of young women.

BACKGROUND: Increased physical activity has been hypothesized to be a means of breast cancer prevention. We examined the associations between physical activity at two different times in life and breast cancer risk. METHODS: We analyzed data from the Nurses' Health Study II, a prospective study of women aged 25-42 years in 1989. On the baseline survey, women were asked, "While in high school and between the ages 18 and 22 years, how often did you participate in strenuous physical activity at least twice a week?" We averaged answers to these two questions to develop a measure of late adolescent activity. Women were also asked at baseline to report the number of hours per week they currently spent in different nonoccupational activities. During 6 years of follow-up, we identified 372 cases of invasive breast cancer. Data were analyzed by use of multivariate pooled logistic regression to produce relative risk (RR) and confidence intervals (CIs) of being diagnosed with the disease. RESULTS: Women who were more active in late adolescence were not at reduced risk of breast cancer compared with less active women. For those women who reported engaging in strenuous activity at least twice per week for 10-12 months per year in late adolescence, the RR of cancer, compared with those who never engaged in such activity, was 1.1 (95% CI = 0.8-1.6). Similarly, higher levels of recent nonoccupational physical activity were not associated with reduced risk of breast cancer (RR for > or = 7 hours of activity/week relative to < 1 hour/week = 1.1; 95% CI = 0.8-1.5). CONCLUSION: Our findings do not support a link between physical activity, in late adolescence or in the recent past, and breast cancer risk among young adult women.

Adolescent↗