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Biomedical subjects

David J Hunter

Publications and source records attributed to David J Hunter.

At least 91 records · Page 5Linked to original sources
PubMed2005

Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension.

Hypertension during pregnancy increases fetal growth retardation, preterm deliveries, and perinatal deaths, and yet its causes remain unclear. In HIV-infected women, preterm birth additionally increases the risk of HIV transmission to the infant. Oxidative stress and endothelial cell dysfunction of the placenta have been implicated in the development of hypertension during pregnancy. Vitamin intake can reduce oxidative stress and improve endothelial function. We therefore evaluated the effect of multivitamin (20 mg thiamine, 20 mg riboflavin, 25 mg B-6, 50 microg B-12, 500 mg C, 30 mg E, and 0.8 mg folic acid) and vitamin A supplements (30 mg beta-carotene plus 5000 IU preformed vitamin A) in relation to hypertension during pregnancy (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg at any time during pregnancy). In a double-blind, placebo-controlled, randomized, clinical trial, conducted among 1078 HIV-positive pregnant Tanzanian women, those who received multivitamins were 38% less likely to develop hypertension during pregnancy than those who did not [relative risk (RR) = 0.62, 95% CI 0.40-0.94, P = 0.03]. There was no overall effect of vitamin A on hypertension during pregnancy (RR = 1.00, 95% CI 0.66-1.51, P = 0.98). Hypertension during pregnancy was more likely in women with high baseline systolic blood pressure (>120 vs. < or = 120 mm Hg) (RR = 6.02, 95%CI 2.59-13.97, P < 0.001), and those with higher mid-upper arm circumference (RR = 1.12, 95% CI 1.04-1.19, P = 0.002). Taking multivitamins containing vitamins B, C, and E during pregnancy may be an inexpensive and effective strategy to improve the health of the mother and baby.

Adult↗
PubMed2005

The erbB2/HER2/neu receptor polymorphism Ile655Val and breast cancer risk.

The erbB2 (HER2/neu) gene is found amplified in tumours. A single nucleotide polymorphism at codon 655 (Ile655Val) has been studied in a number of case-control studies with respect to breast cancer risk, with conflicting results. The aim of the present study was to examine the association between this polymorphism and breast cancer risk in a prospective, predominantly Caucasian cohort of women, the Nurses' Health Study. We genotyped the Ile655Val single nucleotide polymorphism (rs1801200) in 1271 incident breast cancer cases, and 1667 controls who were selected from the Nurses' Health Study blood cohort. Controls were matched to cases on age, menopausal status, fasting status and postmenopausal hormone use at blood draw. An inverse association was observed between the Val/Val genotype and breast cancer risk (Val/Val versus Ile/Ile odds ratio=0.68, 95% confidence interval 0.47-0.98). We conclude that this polymorphism is not associated with an increase in breast cancer risk, and may in fact be associated with a modest decrease in risk.

Adult↗
PubMed2005

Diseases of comfort: primary cause of death in the 22nd century.

CONTEXT: The world has started to feel the impact of a global chronic disease epidemic, which is putting pressure on our health care systems. If uncurbed, a new generation of "diseases of comfort" (such as those chronic diseases caused by obesity and physical inactivity) will become a major public health problem in this and the next century. OBJECTIVE: To describe the concept, causes, and prevention and control strategies of diseases of comfort. METHODS: Brokered by a senior research scientist specialised in knowledge translation, a chair, a president, and a past president of national public health associations contributed their views on the subject. RESULTS: Diseases of comfort have emerged as a price of living in a modern society. It is inevitable that these diseases will become more common and more disabling if human "progress" and civilisation continue toward better (more comfortable) living, without necessarily considering their effects on health. Modern technology must be combined with education, legislation, intersectoral action, and community involvement to create built and social environments that encourage, and make easy, walking, physical activity, and nutritious food choices, to reduce the health damaging effects of modern society for all citizens and not only the few. CONCLUSIONS: Public health needs to be more passionate about the health issues caused by human progress and adopt a health promotion stance, challenging the assumptions behind the notion of social "progress" that is giving rise to the burden of chronic disease and developing the skills to create more health promoting societies in which individual health thrives.

Cause of Death↗
PubMed2005

Fiber intake and incidence of colorectal cancer among 76,947 women and 47,279 men.

Prospective cohort studies have consistently found no important link between fiber intake and risk of colorectal cancer. The recent large, prospective European Prospective Investigation into Cancer and Nutrition has challenged this paradigm by suggesting significant protection by high fiber intake. We prospectively investigated the association of fiber intake with the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (76,947 women) and the Health Professionals Follow-up Study (47,279 men). Diet was assessed repeatedly in 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon and rectum was ascertained up to the year 2000. Relative risk estimates were calculated using a Cox proportional hazards model simultaneously controlling for potential confounding variables. During follow-up including 1.8 million person-years and 1,596 cases of colorectal cancer, we found little association with fiber intake after controlling for confounding variables. The hazard ratio for a 5-g/d increase in fiber intake was 0.91 (95% confidence interval, 0.87-0.95) after adjusting for covariates used in the European Prospective Investigation into Cancer and Nutrition study and 0.99 (95% confidence interval, 0.95-1.04) after adjusting for additional confounding variables. Our data from two large prospective cohorts with long follow-up and repeated assessment of fiber intake and of a large number of potential confounding variables do not indicate an important association between fiber intake and colorectal cancer but reveal considerable confounding by other dietary and lifestyle factors.

Adult↗
PubMed2005

APC Asp1822Val and Gly2502Ser polymorphisms and risk of colorectal cancer and adenoma.

Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene is an important initiating factor in the early stages of the adenoma-carcinoma sequence. The aim of this study was to investigate the two most common APC variants (Asp1822Val and Gly2502Ser) and their association with colorectal cancer and adenoma and whether these relationships are influenced by dietary and lifestyle factors. We analyzed 556 adenoma cases and 557 matched controls and 197 cancer cases and 490 matched controls nested within the Nurses' Health Study cohort, 274 cancer cases and 456 matched controls nested within the Physicians' Health Study cohort, and 375 adenoma cases and 724 matched controls nested within the Health Professionals Follow-up Study cohort. APC Asp1822Val and Gly2502Ser polymorphisms were not associated with risk of colorectal cancer or adenoma. For colorectal cancer, a significant interaction was found between Asp1822Val genotype and postmenopausal hormone (PMH) use among postmenopausal women (P(interaction) = 0.03). Current PMH use was associated with reduced risk overall and a statistically significant lower risk of colorectal cancer among carriers of one or two copies of the APC 1822Val allele (relative risk, 0.46; 95% confidence interval, 0.24-0.88) relative to wild-type never or past PMH users. Our results suggest that cigarette smoking, alcohol intake, and family history of colorectal cancer were positively associated and regular aspirin intake was inversely associated with colorectal adenoma in men and women. No gene-environment interactions were observed with these risk factors or with other dietary risk factors previously hypothesized to interact with the APC Asp1822Val polymorphism.

Adenoma↗
PubMed2005

Genetic variation in XPD, sun exposure, and risk of skin cancer.

The XPD gene is involved in the nucleotide excision repair pathway removing DNA photoproducts induced by UV radiation. Genetic variation in XPD may exert a subtle effect on DNA repair capacity. We assessed the associations between two common nonsynonymous polymorphisms (Asp312Asn and Lys751Gln) with skin cancer risk in a nested case-control study within the Nurses' Health Study (219 melanoma, 286 squamous cell carcinoma, 300 basal cell carcinoma, and 874 controls) along with exploratory analysis on the haplotype structure of the XPD gene. There were inverse associations between the Lys751Gln and Asp312Asn polymorphisms and the risks of melanoma and squamous cell carcinoma. No association was observed between these two polymorphisms and basal cell carcinoma risk. We also observed that the association of the 751Gln allele with melanoma risk was modified by lifetime severe sunburns, cumulative sun exposure with a bathing suit, and constitutional susceptibility score (P for interaction = 0.03, 0.04, and 0.02 respectively). Similar interactions were also observed for the Asp312Asn. Our data suggest these two XPD nonsynonymous polymorphisms may be associated with skin cancer risk, especially for melanoma.

Adult↗
PubMed2005

Menstrual cycle characteristics and incidence of premenopausal breast cancer.

BACKGROUND: Epidemiologic studies have indicated that menstrual cycle characteristics such as age at menarche and age at menopause are associated with breast cancer risk. Anovulation, which is more common with long or irregular cycles, has been hypothesized to reduce the incidence of breast cancer. METHODS: We analyzed data from the Nurses' Health Study II, a cohort of 116,671 female registered nurses ages 25 to 42 years at baseline. Information on menstrual cycle characteristics was assessed in 1989 and 1993, and incident cases of premenopausal breast cancer were ascertained through 2001. RESULTS: During 1,135,496 person-years of follow-up (1989-2001), 1,163 incident cases of invasive premenopausal breast cancer were diagnosed. Overall, women with long menstrual cycles at ages 18 to 22 years (>32 days or too irregular to estimate) did not experience a significantly lower breast cancer risk compared with women with normal cycle lengths (26-31 days) at that age [covariate-adjusted hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.79-1.06]. Among women ages <40 years, those with menstrual cycles lasting >32 days or too irregular to estimate at ages 18 to 22 years had a decreased incidence of breast cancer (covariate-adjusted HR, 0.71; 95% CI, 0.53-0.97). Current menstrual cycle characteristics were not associated with breast cancer incidence. CONCLUSION: Overall, longer or irregular cycles at ages 18 to 22 years or in early adulthood were not associated with reduced premenopausal breast cancer risk. However, longer menstrual cycles at ages 18 to 22 years were associated with a lower incidence of premenopausal breast cancer before age 40.

Adult↗
PubMed2005

Folate intake and risk of breast cancer characterized by hormone receptor status.

Folate plays an important role in DNA methylation, and aberrant methylation of the estrogen receptor (ER) gene may be related to the loss of ER gene expression in breast tumors. Thus, deficient folate status has been hypothesized to be associated primarily with ER gene-negative breast tumors, but data relating folate intake to breast cancer risk according to ER status are sparse. We conducted a prospective cohort analysis of folate intake among 88,744 women in the Nurses' Health Study who completed a food frequency questionnaire in 1980 and every 2 to 4 years thereafter. During 20 years of follow-up, 2,812 ER+ and 985 ER- invasive breast cancer cases were documented. Higher total folate intake was significantly associated with lower risk of developing ER- but not ER+ breast cancer; the multivariable relative risks (RR) and 95% confidence intervals (95% CI) comparing the highest to the lowest quintile were 0.81 (0.66-0.99) for ER- tumors and 1.00 (0.89-1.14) for ER+ tumors. The inverse association between total folate intake and ER- breast cancer was mainly present among women consuming at least 15 g/d of alcohol (multivariable RR, 0.46; 95% CI,=0.25-0.86; top versus bottom quintile). These findings support the hypothesis that higher folate intake reduces the risk of developing ER- breast cancer. Ensuring adequate folate intake seems particularly important for women at higher risk of breast cancer because of alcohol consumption.

Adult↗
PubMed2005

Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies.

Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions, increased consumption may reduce the risk of ovarian cancer. Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent. We analyzed and pooled the primary data from 12 prospective studies in North America and Europe. Fruit and vegetable intake was measured at baseline in each study using a validated food-frequency questionnaire. To summarize the association between fruit and vegetable intake and ovarian cancer, study-specific relative risks (RR) were estimated using the Cox proportional hazards model, and then combined using a random-effects model. Among 560,441 women, 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies. Total fruit intake was not associated with ovarian cancer risk-the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [95% confidence interval (95% CI), 0.92-1.21; P value, test for trend = 0.73; P value, test for between-studies heterogeneity = 0.74]. Similarly, results for total vegetable intake indicated no significant association (pooled multivariate RR, 0.90; 95% CI, 0.78-1.04, for the highest versus the lowest quartile; P value, test for trend = 0.06; P value, test for between-studies heterogeneity = 0.31). Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk. Associations for total fruits and vegetables were similar for different histologic types. These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer.

Adult↗
PubMed2005

Associations between polymorphisms in the vitamin D receptor and breast cancer risk.

Biological and epidemiologic data suggest that vitamin D levels may influence breast cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. Because functional data exist on FOK1 and previous studies have suggested a relation between BSM1 and breast cancer risk, we evaluated the associations of the FOK1 and BSM1 VDR polymorphisms and breast cancer risk. In a case-control study nested within the Nurses' Health Study, we genotyped 1,234 incident cases (diagnosed between return of a blood sample in 1989-1990 and June 1, 2000) and 1,676 controls for FOK1, and 1,180 cases and 1,547 controls for BSM1. We observed a significantly increased risk of breast cancer among carriers of the ff genotype of FOK1 (multivariate odds ratio, 1.34; 95% confidence intervals, 1.06-1.69) compared with those with FF. We did not observe an association between polymorphisms in BSM1 and breast cancer risk (multivariate odds ratio, 0.93; 95% confidence intervals, 0.72-1.20) for BB versus bb). The FOK1 association did not vary significantly by menopausal status, estrogen, and progesterone receptor status of the tumors, or plasma levels of 25 hydroxyvitamin D or 1,25 dihydroxyvitamin D. Our results suggest that the VDR may be a mediator of breast cancer risk and could represent a target for cancer prevention efforts.

Adult↗
PubMed2005

Adverse perinatal outcomes of HIV-1-infected women in relation to malaria parasitemia in maternal and umbilical cord blood.

Malaria infection during pregnancy increases the risk of adverse birth outcomes among HIV-infected women. The role of umbilical cord parasitemia is not well characterized. We examined the risk of adverse perinatal outcomes in relation to maternal or umbilical cord Plasmodium falciparum parasitemia among 275 HIV-infected women from Tanzania, who participated in a randomized trial of zinc supplementation during pregnancy. Maternal parasitemia (> or = 1/microL) at the first antenatal visit was associated with increased risk of low birth weight < 2,500 g (adjusted relative risk [ARR] = 2.66; P = 0.01) and preterm delivery < 37 weeks (ARR = 1.87; P = 0.06). Maternal parasitemia at delivery was associated with preterm delivery (ARR = 2.27; P = 0.008), intrauterine growth retardation (ARR = 1.92; P = 0.03), and neonatal death (ARR = 3.22; P = 0.07). Cord parasitemia was associated with a large and significant increase in the risk of neonatal death (ARR = 8.75; P = 0.003). Maternal parasitemia at the first antenatal visit was strongly related to parasitemia at delivery, and the latter was associated with cord blood parasitemia. CD4 cell counts, parity, or assignment to the zinc arm (25 mg daily) were not associated with parasitemia in maternal or cord blood at delivery. Successful treatment of HIV-infected women who present to the first prenatal visit with malaria parasitemia and avoidance of reinfection are likely to decrease the risk of adverse outcomes during pregnancy and the early postpartum period. Cord blood parasitemia is a strong predictor of neonatal death. The potential effect of zinc supplementation on clinical malaria outcomes deserves future investigation.

Adult↗
PubMed2005

Structural factors associated with malalignment in knee osteoarthritis: the Boston osteoarthritis knee study.

OBJECTIVE: Osteoarthritis (OA) is a multifactorial condition. The progression of knee OA is determined in part by mechanical effects on local structures. One of the mechanical influences on cartilage loss is limb alignment. We explored the structural factors associated with malalignment in subjects with symptomatic OA. METHODS: We conducted a cross-sectional assessment using The Boston Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA. Baseline assessments included knee magnetic resonance imaging (MRI) and information on weight and height. Long-limb radiographs to assess mechanical alignment were obtained at 15 months. Subarticular bone attrition, meniscal degeneration, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, marginal osteophytes, and cartilage morphology were assessed on MRI using a semiquantitative, multi-feature scoring method (Whole-Organ MRI Score) for whole-organ evaluation of the knee that is applicable to conventional MRI techniques. We also quantified the following meniscal position measures on coronal MRI images in both medial and lateral compartments: subluxation, meniscal height, and meniscal covering of the tibial plateau. Using the long-limb radiographs, mechanical alignment was measured in degrees on a continuous scale. The purpose of this cross-sectional analysis was to determine the individual and relative contribution of various structural factors to alignment of the lower extremity. We assessed the cross-sectional association between various structural factors and alignment of the lower extremity using a linear regression model. RESULTS: The 162 subjects with all measures acquired had a mean age of 67.0 years (SD 9.2), body mass index 31.4 (SD 5.6); 30% were female and 77% of knees had a Kellgren-Lawrence grade > or = 2. The main univariate determinants of varus alignment in decreasing order of influence were medial bone attrition, medial meniscal degeneration, medial meniscal subluxation, and medial tibiofemoral cartilage loss. Multivariable analysis revealed that medial bone attrition and medial tibiofemoral cartilage loss explained more of the variance in varus malalignment than other variables. The main univariate determinants of valgus malalignment in decreasing order of influence were lateral tibiofemoral cartilage loss, lateral osteophyte score, and lateral meniscal degeneration. CONCLUSION: Cartilage loss has been thought to be the major determinant of alignment. We found that other factors including meniscal degeneration and position, bone attrition, osteophytes, and ligament damage contribute to the variance of malalignment. Further longitudinal analysis is required to determine cause and effect relationships. This should assist researchers in determining strategies to ameliorate the potent effects of this mechanical disturbance.

Aged↗
PubMed2004

Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer.

INTRODUCTION: Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. METHOD: We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). RESULTS: One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02-1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. CONCLUSIONS: We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear.

Adult↗
PubMed2004

Primary care trusts.

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Health Facility Merger↗
PubMed2004

Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors.

The authors investigated the relations of demographic, anthropometric, and lifestyle factors with endometriosis in the Nurses' Health Study II prospective cohort. During 10 years of follow-up (1989-1999), 1,721 cases of laparoscopically confirmed endometriosis were reported among women with no past infertility. The incidence rate was greatest among women aged 25-29 years and lowest among women over 44 years (p(trend) < 0.0001). In multivariate Cox proportional hazards models, African-American women had a lower rate of disease compared with Caucasian women (rate ratio = 0.6, 95% confidence interval: 0.4, 0.9). The authors also observed an inverse relation with body mass index at age 18 years (for body mass index of >30 vs. 19-20.4 kg/m(2): rate ratio = 0.8, 95% confidence interval: 0.6, 1.1; p(trend) = 0.004) and with current alcohol intake (for >10 vs. 0 g/day: rate ratio = 0.7, 95% confidence interval: 0.6, 0.8; p(trend) < 0.0001) but no association with height, waist/hip ratio, or caffeine intake. An inverse relation with current body mass index and current cigarette smoking was observed only when cases were concurrently infertile. The authors conclude that age, race, body mass index, alcohol use, and cigarette smoking are associated with the incidence of endometriosis and that some of these relations may differ by infertility status at the time of laparoscopic diagnosis.

Adult↗