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D J Hunter

Publications and source records attributed to D J Hunter.

At least 127 records · Page 7Linked to original sources
PubMed1998

A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer.

Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environment interaction with red meat intake among participants in the prospective Physicians' Health Study. Baseline blood samples from 212 men subsequently diagnosed with colorectal cancer during 13 years of follow-up were genotyped, along with 221 controls. NAT genotypes were analyzed by a PCR-restriction fragment length polymorphism method. Effect modification of the relation of red meat intake and risk of colorectal cancer by NAT genotype was assessed using conditional logistic regression. There was no overall independent association of NAT acetylation genotypes and colorectal cancer risk. The relative risks for the rapid acetylation genotype were 0.93 [95% confidence interval (CI), 0.61-1.42] for NAT1, 0.80 (95% CI, 0.53-1.19) for NAT2, and 0.81 (95% CI, 0.52-1.27) for NAT1/NAT2 combined. We observed a stronger association of red meat intake with cancer risk among NAT rapid acetylators, especially among men 60 years old or older. Among those men who were rapid acetylators for both NAT1 and NAT2, consumption of >1 serving of red meat per day was associated with a relative risk of 5.82 (95% CI, 1.11-30.6) compared with consumption of < or = 0.5 serving per day (P, trend = 0.02). These prospective data, which need to be confirmed in other studies, suggest that polymorphisms in the NAT genes confer differential susceptibility to the effect of red meat consumption on colorectal cancer risk.

Adult↗
PubMed1998

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania.

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.

CD3 Complex↗
PubMed1998

Circulating concentrations of insulin-like growth factor-I and risk of breast cancer.

BACKGROUND: Insulin-like growth factor (IGF)-I, a mitogenic and antiapoptotic peptide, can affect the proliferation of breast epithelial cells, and is thought to have a role in breast cancer. We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer. METHODS: We carried out a nested case-control study within the prospective Nurses' Health Study cohort. Plasma concentrations of IGF-I and IGF binding protein 3 (IGFBP-3) were measured in blood samples collected in 1989-90. We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls. IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors. FINDINGS: There was no association between IGF-I concentrations and breast-cancer risk among the whole study group. In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk (top vs bottom quintile of IGF-I, relative risk 0.85 [95% CI 0.53-1.39]). The relative risk of breast cancer among premenopausal women by IGF-I concentration (top vs bottom tertile) was 2.33 (1.06-5.16; p for trend 0.08). Among premenopausal women less than 50 years old at the time of blood collection, the relative risk was 4.58 (1.75-12.0; p for trend 0.02). After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28, respectively. INTERPRETATION: A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women. Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies. Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect.

Breast Neoplasms↗
PubMed1998

Angular dependence of electron paramagnetic resonances of an azide-NO complex of cytochrome c oxidase: orientation of the haem-copper axis in cytochrome aa3 from ox heart.

The orientation dependence of the EPR signals arising from the azide-nitric oxide complex of cytochrome oxidase was investigated using oriented multilayers of mitochondrial membranes from ox heart. Variations in line shape of the DeltaMS=1 signal of the triplet state were apparent, whilst the DeltaMS=2 transitions between g=4.7 and 3.9 varied in intensity as the angle of the applied magnetic field was varied. These half-field signals were maximal with the field parallel to the membrane plane. A model of the bi-liganded azide-nitric oxide complex has been constructed, in which the nitric oxide is bound to the high-spin haem in a bent configuration, with the Fe-N=O plane at 60-90 degrees to the membrane plane and the azide bound to the copper, distal from the haem. In addition, angular variations of the signals at g'=11 and g' around 3.5, derived from an integer-spin complex, were also observed.

Animals↗
PubMed1998

Menstrual cycle characteristics and history of ovulatory infertility in relation to breast cancer risk in a large cohort of US women.

Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25-42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche > 13 years compared with age < or = 12 years was 0.66 (95% confidence interval (CI) 0.44-0.99). Short and long menstrual cycle lengths at ages 18-22 years were associated with reduced risk. Compared with menstrual cycle length 26-31 days, the multivariate relative risks (95% CIs) for more extreme cycle lengths were: < 26 days, 0.50 (0.25-0.98); 32-39 days, 0.81 (0.51-1.28); and > 39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18-0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18-0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer.

Adult↗
PubMed1998

Alcohol and breast cancer in women: a pooled analysis of cohort studies.

OBJECTIVE: To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. DATA SOURCES: We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. DATA EXTRACTION: Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. DATA SYNTHESIS: For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. CONCLUSIONS: Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

Alcohol Drinking↗
PubMed1998

Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses' Health Study.

Environmental exposure to carcinogens may contribute to increasing breast cancer rates and geographic variation in breast cancer incidence in the United States. One class of chemicals that has received much attention are the polyaromatic hydrocarbons that are ubiquitous in the environment and occur in cigarette smoke. The cytochrome P450 1A1 (CYP1A1) gene codes for an enzyme that contributes to aryl hydrocarbon hydroxylase activity, which is involved in the metabolism of polyaromatic hydrocarbons. Genotypic variants of CYP1A1 have been associated with increased aryl hydrocarbon hydroxylase activity, and some epidemiological studies suggest that women with the variant genotype(s) are at increased risk for breast cancer. We prospectively evaluated the associations between the CYP1A1 polymorphisms and breast cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case-control study nested within the Nurses' Health Study. We analyzed the T-->C transition at nucleotide 6235 (MspI) and the A-->G transition at nucleotide 4889 (exon 7) in CYP1A1 by PCR-RFLP assays among 466 incident breast cancer cases and 466 matched controls. Relative risks (RRs) and 95% confidence intervals (CIs) were used to quantify the risk of breast cancer among subjects who had at least one variant allele relative to subjects who were homozygous for the wild-type allele, using conditional logistic regression. No overall increase in breast cancer risk with the variant CYP1A1 genotypes was apparent (RR(MspI), 1.05; 95% CI, 0.74-1.50 and RR(exon7), 0.88; 95% CI, 0.58-1.33). However, a suggestive increase in breast cancer risk was observed among women who had commenced smoking before the age of 18 and had the CYP1A1-MspI variant genotype compared to nonsmokers who were homozygous wild type for the polymorphism (RR, 5.65; 95% CI, 1.50-21.3; percentage of all breast cancer cases attributable to this risk factor, 2.5%). A similar gene-environment association was observed for the exon 7 polymorphism (RR, 3.61; 95% CI, 1.11-11.7; percentage of all breast cancer cases attributable to this risk factor, 2.2%). These data are compatible with the hypothesis that cigarette smoking early in life is a modifiable cause of breast cancer in a subpopulation of genetically susceptible women. However, the proportion of breast cancer attributable to cigarette smoking at a young age among Caucasian women with the variant form of the CYP1A1 polymorphisms is low.

Adult↗
PubMed1998

The incidence of HIV infection among women using family planning methods in Dar es Salaam, Tanzania.

OBJECTIVES: To determine the risk factors for HIV seroconversion and assess the association between contraceptive use and HIV infection among women attending three large family planning clinics in Dar es Salaam, Tanzania. DESIGN: Prospective cohort study. METHODS: Between 1992 and 1995, 2471 HIV-negative women were followed prospectively. Information about sociodemographic characteristics, sexual behavior, contraceptive use and other risk factors was collected at recruitment and updated at follow-up visits. At the end of the study, specimens were collected for HIV testing and laboratory diagnosis of sexually transmitted diseases. RESULTS: The overall HIV incidence was 3.4 per 100 person-years [95% confidence interval (Cl), 2.6-4.1]. The risk of HIV seroconversion decreased with increasing age (P=0.04, test for trend). Women reporting three or more sex partners during the follow-up period had the highest risk of HIV [age-adjusted relative risk (RR), 4.89; 95% Cl, 2.61-9.17]. Having an uncircumcised husband was associated with a significantly increased risk of HIV (age-adjusted RR, 3.60; 95% Cl, 1.12-11.59). The risk of HIV was also significantly increased among women with gonorrhoea (age-adjusted RR, 3.51; 95% Cl, 1.60-7.71) and candidiasis at baseline (age-adjusted RR, 1.98; 95% Cl, 1.17-3.33) and among women reporting alcohol consumption during the follow-up period. After controlling for other risk factors, the risk of HIV infection amongst users of oral contraceptive, intrauterine device and injectable contraceptive was not significantly increased. Similarly, there was no significant trend associated with increasing duration of use of any of these contraceptive methods. CONCLUSION: These findings confirm that a large number of new HIV infections continue to occur in this population. Reassuringly, no significant association was observed between HIV and use of specific contraceptive methods. Interventions to reduce further spread of HIV are still urgently needed.

Adolescent↗
PubMed1998

Genes and environment in the etiology of colorectal cancer.

Environmental factors, including diet, are important in the etiology of colorectal cancer. Genetic pathways of hereditary and sporadic bowel cancer are being elucidated. Highly penetrant mutations in certain genes, such as mismatch repair genes, play a major role in development of hereditary colorectal cancer, while interactions between low penetrance polymorphisms in carcinogen-metabolizing enzymes and environmental factors may identify susceptible subgroups and shed light on the etiology of sporadic colorectal cancers. In this review we summarize the current state of knowledge regarding the role of gene-environment interactions in development of colorectal cancer and discuss areas of particular promise, as well the limitations of these studies.

Colorectal Neoplasms↗
PubMed1998

A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata.

OBJECTIVE: To investigate the risk of uterine leiomyomata in relation to reproductive factors and oral contraceptive use. DESIGN: A prospective study. SETTING: A cohort of female registered nurses from 14 states in the United States who completed mailed questionnaires in 1989, 1991, and 1993. PATIENT(S): Premenopausal nurses (n=95,061) aged 25-42 years with intact uteri and no history of diagnosed uterine leiomyomata or cancer in 1989. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of self-reported uterine leiomyomata confirmed by ultrasound or hysterectomy. In a sample of 243 cases, 93% of the self-reported diagnoses were confirmed in the medical record. RESULT(S): During 326,116 person-years of follow-up, 3,006 cases of uterine leiomyomata, confirmed by ultrasound or hysterectomy, were reported. After adjustment for other risk factors, the risk of uterine leiomyomata was significantly inversely associated with age at menarche, parity, and age at first birth, and positively associated with a history of infertility and years since last birth. The only notable association with any aspect of oral contraceptive use was a significantly elevated risk among women who first used oral contraceptives at ages 13-16 years compared with those who had never used oral contraceptives. CONCLUSION(S): Reproductive factors and oral contraceptive use at a young age influence the risk of uterine leiomyomata among premenopausal women.

Adult↗
PubMed1998

A common mutation in the methylenetetrahydrofolate reductase gene and risk of coronary heart disease: results among U.S. men.

OBJECTIVES: We examined the risk of coronary heart disease associated with homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase gene. BACKGROUND: The mutation increases plasma homocysteine levels by impairing its remethylation. Increased plasma homocysteine is an independent risk factor for cardiovascular disease. METHODS: This was a case-control study nested within the Health Professionals Follow-up Study. In 1986, 44,940 U.S. male health professionals, aged 40 to 75 years and free from diagnosed cardiovascular disease, provided detailed information on usual dietary intake, including intake of folate, vitamins B2, B6 and B12, and methionine. Between 1993 and 1995, blood samples were provided by approximately 40% of the participants. We compared data from 500 men with nonfatal coronary heart disease, diagnosed between 1986 and 1992, with data from 500 age-matched control subjects who were free of diagnosed cardiovascular disease at the time of the matched case subject's diagnosis. RESULTS: Frequencies of homozygosity (+/+) and heterozygosity (+/-) for the mutation were 12.2% and 41.8% in case subjects and 14.4% and 40.0% in control subjects. With subjects homozygous (-/-) or heterozygous (+/-) for the wildtype allele as a reference and matched by age, the odds ratio of coronary heart disease was 0.83 (95% confidence interval, 0.57 to 1.19) for +/+ subjects. The odds ratio was unchanged after adjustment for smoking and other risk factors for coronary heart disease. Odds ratios were also calculated within strata for intake of vitamins involved in homocysteine metabolism or methionine, the metabolic precursor of homocysteine. The +/+ genotype was not directly associated with risk of coronary heart disease among men with low (that is, within the lowest quartile) intake (<301 microg/d) of folate, the substrate for methylenetetrahydrofolate reductase; low intake (<1.8 mg/d) of vitamin B2, the cofactor for methylenetetrahydrofolate reductase; low intake (<8.0 microg/d) of vitamin B12, the cofactor for remethylation; low intake (<2.1 mg/d) of vitamin B6, the cofactor in the catabolic pathway of homocysteine; or high intake (>2.4 g/d) of methionine. CONCLUSIONS: In this generally well-nourished population, men with the +/+ genotype for the C677T mutation in the methylenetetrahydrofolate reductase gene have no increase in risk of coronary heart disease, even when intake of folate or other B vitamins is low.

Adult↗
PubMed1998

The relation between dietary intake and adipose tissue composition of selected fatty acids in US women.

We compared fatty acid amounts in adipose tissue with fatty acid intake calculated from 2 separate weeks of diet recording and two food-frequency questionnaires for 140 participants in the Nurses' Health Study. Our results showed that the amounts of polyunsaturated and trans fatty acids in adipose tissue reflect dietary intake and confirm those of previous studies. The correlation between the polyunsaturated fatty acid content of adipose tissue and polyunsaturated fatty acid intake from the average of the two food-frequency questionnaires was 0.40; this correlation for trans fatty acids was also 0.40. Linolenic acid amounts in adipose tissue were also moderately correlated with intake from the average of the food-frequency questionnaires (r = 0.34). An estimate of trans fatty acid intake from vegetable sources correlated much more strongly with adipose trans fatty acids than did an estimate of trans fatty acids from animal sources. Adipose tissue aspirates can be used to indicate intake of exogenous fatty acids.

Adipose Tissue↗
PubMed1998

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma.

We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1998

Environmental risk factors and female breast cancer.

The increasing incidence of breast cancer in the United States and the international variation in risk have led to speculation that environmental risk factors are an important cause of breast cancer. We review the epidemiologic evidence on the breast cancer risk associated with ambient environmental exposures experienced passively by the US population, and discuss the difficulties associated with measurement of specific exposures in environmental studies. We review geographic variation of breast cancer rates in the United States, and exposure to organochlorines, ionizing and electromagnetic radiation, and passive smoking. Results are inconclusive but do not support a major role of environmental risk factors in the etiology of breast cancer.

Breast Neoplasms↗
PubMed1998

Health care reform.

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Cooperative Behavior↗
PubMed1998

Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians.

Prostatic cells express vitamin D receptor (VDR), which mediates the functions of 1,25-dihydroxyvitamin D. Two recent case-control studies suggested strong inverse associations between two VDR polymorphisms, TaqI and poly(A), and risk of prostate cancer. These two and a third polymorphism, BsmI, are closely linked. In a case-control study nested in the Physicians' Health Study, a randomized double-blind trial of aspirin and beta-carotene among 22,071 United States male physicians, we examined the associations between BsmI and TaqI and prostate cancer risk and whether the associations varied according to age and vitamin D metabolite levels among 372 incident cases and 591 controls. Among controls, the BB genotype was significantly associated with higher 1,25-dihydroxyvitamin D (median = 36.2 pg/ml for the BB versus 33.9 pg/ml for the bb genotype; P = 0.02), suggesting an association of the VDR polymorphisms with VDR function. Overall, we observed no significant associations of these VDR polymorphisms with prostate cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29] for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype, compared with the bb genotype (results were similar for the TaqI polymorphism). Stratification by age (< or = 61 and > 61 years) and tumor aggressiveness showed no significant associations. However, in an analysis restricted to men with plasma 25-hydroxyvitamin D below the median, we observed a 57% reduction (RR = 0.43, 95% CI = 0.19-0.98) in risk for those with the BB versus the bb genotype; the risk reduction was particularly marked among older men (RR = 0.18, 95% CI = 0.05-0.68). We did not observe this inverse association among men with 25-hydroxyvitamin D levels above the median, nor did we observe it among younger men.

Adult↗