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D J Hunter

Publications and source records attributed to D J Hunter.

At least 37 records · Page 2Linked to original sources
PubMed2004

A genome scan for joint-specific hand osteoarthritis susceptibility: The Framingham Study.

OBJECTIVE: Studies investigating hand osteoarthritis (OA) as a single entity have not shown strong linkage of the disease with any chromosomal sites. We undertook this study to test our hypothesis that phenotypes of hand OA may show stronger linkage than has been shown for overall hand OA. METHODS: We performed a factor analysis on measures of hand OA to determine patterns of disease. Using the joint regions identified by this analysis, we performed a genome-wide linkage analysis for OA susceptibility loci using 426 original cohort members and 790 offspring cohort members in 267 pedigrees. Radiographic OA features evaluated included the Kellgren/Lawrence score, osteophytes, and joint space narrowing. Prior to linkage analysis, standardized residuals were computed from regression analysis of each phenotype on age. This was performed separately for each sex and cohort. The variance component model (GeneHunter) was then applied to the normalized scores of the residuals of both sexes and cohorts. RESULTS: There was evidence suggestive of linkage (logarithm of odds [LOD] score >1.5) at 16 sites. Four of these sites had LOD scores >3.0. Two of these sites (identified in the full sample) included a linkage region for OA of the distal interphalangeal (DIP) joint on chromosome 7 (155 cM; LOD score 3.06) and a linkage region for OA of the first carpometacarpal (CMC) joint on chromosome 15 (81 cM; LOD score 6.25). The other 2 sites (identified in women) included a linkage region for OA of the DIP joint on chromosome 1 (202 cM; LOD score 3.03) and a linkage region for OA of the first CMC joint on chromosome 20 (4 cM; LOD score 3.74). CONCLUSION: These data suggest that several chromosomes contain hand OA susceptibility genes and that a joint-specific approach may be more rewarding than a global approach to the genetics of hand OA. Further investigation of these regions is warranted using finer maps and other populations.

Chromosome Mapping↗
PubMed2003

Physical activity and risk of breast cancer in premenopausal women.

Physical activity appears to be inversely related to risk of breast cancer, yet the results remain inconsistent. To evaluate this relation among premenopausal women and examine variation in risk according to level of obesity and use of oral contraceptives (OCs), the authors examined data from the Nurses' Health Study II. During 10 years of follow-up, 849 cases of invasive premenopausal breast cancer were confirmed. Physical activity was assessed by self-report at baseline and during follow-up using a validated questionnaire. Total physical activity was unrelated to risk of breast cancer. Women engaging in >or=27 metabolic equivalent (MET)-h week(-1) had a multivariate-adjusted relative risk (RR) of 1.04 (95% confidence interval (CI) 0.82-1.33) compared to those in the <3 MET-h week(-1) category. Among women with a BMI >or=30 kg m(-2), we observed a significant positive dose-response relation (P=0.04). Activity was unrelated to breast cancer risk at lower levels of BMI. A test for interaction between activity and BMI (<30, >or=30 kg m(-2)) was statistically significant (P=0.02). Among current OC users, higher activity was associated with a non-significantly lower risk of breast cancer (RR=0.59, 95% CI 0.30-1.16 for >or=27 vs <9 MET-h week(-1), P for linear trend=0.14). These results show no overall association between physical activity and risk of breast cancer among premenopausal women, but suggest that the effect of physical activity could be substantially modified by the underlying degree of adiposity. The potential interactions between physical activity, adiposity, and current use of OCs require further study.

Adult↗
PubMed2003

Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins.

BACKGROUND: Osteoarthritis (OA) is a disorder of the whole synovial joint organ. There is growing evidence of the importance of bone turnover in OA, and human studies have demonstrated that the subchondral bone is metabolically active in OA. The aim of this study was to assess the relationships of radiographic knee OA with altered bone turnover and calcium regulation. METHODS: We performed a matched and unmatched case-control study using twins assessed for OA. The subjects were 1644 female Caucasian twin pairs (266 monozygotic and 556 dizygotic) aged 24-79 yr from the St Thomas' UK Adult Twin Registry. Assays for measures of bone turnover [bone-specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline (DPD)] and calcium regulation [serum parathyroid hormone (PTH), 25-hydroxyvitamin D, serum calcium, serum magnesium and serum phosphate] were performed. The radiological features of knee OA were graded on a four-point scale (0-3) for osteophytes and a five-point scale (0-4) for Kellgren and Lawrence classification. Adjustment for age, body mass index (BMI) and relatedness was made. Conditional logistic regression analysis was also used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for having radiological features of knee OA per standardized unit difference of serum variable between twins. RESULTS: Of the 1644 women studied, 474 (28.8%) had radiological evidence of knee osteophytes. There was evidence of increased bone turnover, increased PTH levels and decreased vitamin D levels in this group compared with those without osteophytes. No association was seen with joint space loss. After adjusting for age, BMI and relatedness, all of the differences disappeared except for a significant increase 10% in urinary DPD (P = 0.04). Discordant twin pair analysis (performed on a subgroup of 229 pairs) confirmed modest increases in bone resorption indicated by urinary DPD (OR 1.67, 95% CI 0.88-3.16) and a significant decrease in serum magnesium (OR 0.65, 95% CI 0.46-0.92) in the co-twins with OA. CONCLUSION: Bone resorption is increased in women with knee OA, consistent with metabolically active subchondral bone. However, bone formation, vitamin D and calcium regulation were not different after adjusting for age and BMI. The results suggest that bone resorption is increased in the presence of OA. Although we cannot clearly differentiate a cause or effect relationship, these results suggest that this is related to disease mechanisms and point to potential diagnostic or therapeutic avenues for bone resorption in OA.

Adult↗
PubMed2003

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women.

Within the two Nurses' Health Study cohorts of US women, we examined whether higher intakes of vitamin C, vitamin E, retinol, or individual tocopherols or carotenoids are associated with a lower risk of melanoma. We confirmed 414 cases of invasive melanoma among over 162,000 Caucasian women aged 25-77 years during more than 1.6 million person-years of follow-up. Diet was measured every 4 years with a food frequency questionnaire and supplement use was reported every 2 years. Several measures of sun sensitivity were assessed and included in proportional hazards models. We found that vitamins A, C, E and their individual components were not associated with a lower risk of melanoma. Only retinol intake from foods plus supplements appeared protective within a subgroup of women who were otherwise at low risk based on nondietary factors (relative risk (RR)=0.39, 95% confidence interval (CI) 0.22-0.71 for >/=1,800 vs 400 microg day(-1), P for linear trend=0.01). Contrary to expectation, we observed higher risks of melanoma with greater intakes of vitamin C from food only (RR=1.43, 95% CI 1.01-2.00 for >/=175 vs <90 mg day(-1), P for linear trend=0.05) and a significant positive dose-response with frequency of orange juice consumption (P=0.008). Further research is needed to determine whether another component in foods such as orange juice may contribute to an increase in risk.

Adult↗
PubMed2003

The association of cartilage volume with knee pain.

OBJECTIVE: Whilst the characteristic pathologic feature of OA is the loss of hyaline cartilage, prior studies have demonstrated a poor relationship between severity of reported knee pain and degree of radiographic change. The aim of this study was to examine the association between knee symptoms and MRI cartilage volume. DESIGN: A cross-sectional study was performed to assess the association between knee symptoms and MRI cartilage volume in an unselected, community based population. The subjects were 133 postmenopausal females. The subjects had a T2-weighted fat saturated sagittal gradient-echo MRI performed of their right knee. Femoral, tibial and patella cartilage volumes were measured using three-dimensional (3D) Slicer, a software that facilitates semi-automatic segmentation, generation of 3D surface models and quantitative analysis. Qualitative data relating to symptoms, stiffness, pain, physical dysfunction and the quality of life using the WOMAC were recorded. The statistical analyses conducted to determine measures of association between knee pain/symptoms and cartilage volume were correlation, multiple regression and inter-quartile regression. RESULTS: Assessment of the association between patella cartilage volume and the WOMAC domains showed an inverse relationship between patella cartilage volume and pain, function and global score in a model including body mass index, physical activity and leg extensor power (all P=0.01). Inter-quartile regression comparing the lowest 25% with highest 25% patella cartilage volume demonstrated a stronger inverse relationship (P=0.005). CONCLUSION: This study suggests that alterations in patella volume are associated with pain, function and global scores of the WOMAC. In participants with more knee pain, there was an association with severity of patella cartilage reduction. Other MRI cartilage volume features were not strongly associated with WOMAC sub-scores.

Aged↗
PubMed2002

MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk of PD.

BACKGROUND: A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele. METHODS: The authors studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men aged 40 to 75 in 1986). They identified new PD cases through 1996, selected random control subjects matched on age and study cohort, and obtained DNA samples from blood or buccal smears from 85% of the eligible cases and 84% of the control subjects. They included genotypes from 214 cases and 449 control subjects, all Caucasian. RESULTS: The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA and COMT(HH). There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes. CONCLUSION: The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD, either by itself or by interacting with smoking.

Adult↗
PubMed2002

HIV status and sociodemographic correlates of maternal body size and wasting during pregnancy.

OBJECTIVE: To examine HIV status and sociodemographic variables as correlates of body size (height, body mass index (BMI), and mid-upper-arm circumference (MUAC)) and wasting (MUAC <22 cm) in pregnant women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam, Tanzania. SUBJECTS: Women presenting for first prenatal visit before the 23rd week of gestation, between April 1995 and July 1997 (n=13 760). RESULTS: Mean MUAC, BMI and height were 25.5 cm, 23.5 kg/m(2) and 155.1 cm, respectively. The prevalence of HIV infection was 13.1% and the overall prevalence of wasting was 4.7%. Wasting was 34% (95% CI=3%, 73%) more prevalent among HIV-infected than in uninfected mothers, after adjusting for week of gestation, height and sociodemographic indicators. The risk of wasting associated with HIV infection was highest among women with low level of education or unable to contribute to the household income. From a multiple linear regression model, BMI was positively associated with mother's age, level of education and money spent on food, but not with HIV infection, after adjusting for week of gestation. In multivariate analysis, height increased monotonically by categories of maternal age and level of education, and was also positively correlated with the ability to contribute to household income, the amount of money spent on food per person per day, and having a professional partner. CONCLUSION: HIV infection is a significant risk factor for wasting among pregnant women, particularly in groups of low socioeconomic status (SES). SES indicators are strongly correlated with maternal height and with BMI during the first and second trimesters of pregnancy independently of HIV status. SPONSORSHIP: The National Institute of Child Health and Human Development (NICHD R01 32257), and the Fogarty International Center (NIH D43 TW00004).

Adolescent↗
PubMed2001

Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study.

CONTEXT: Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). OBJECTIVE: To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2), and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. DESIGN, SETTING, AND SUBJECTS: Prospective, nested case-control study. Of 62 439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 1989-1990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. MAIN OUTCOME MEASURE: Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. RESULTS: We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P =.03), EBNA-2 (GMT, 91 vs 40; P =.01), and EA-D (15.9 vs 5.9; P =.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.7-3.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8 (95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. CONCLUSIONS: Our results support a role of EBV in the etiology of MS.

Adult↗
PubMed2001

Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus.

CONTEXT: Although oligomenorrhea has been associated cross-sectionally with insulin resistance and glucose intolerance, it is not known whether oligomenorrhea is a marker for increased future risk of type 2 diabetes mellitus (DM). OBJECTIVE: To prospectively assess risk of type 2 DM in women with a history of long or highly irregular menstrual cycles. DESIGN AND SETTING: The Nurses' Health Study II, a prospective observational cohort study. PARTICIPANTS: A total of 101 073 women who had no prior history of DM and who reported their usual menstrual cycle pattern at age 18 to 22 years on the baseline (1989) questionnaire. MAIN OUTCOME MEASURE: Incident reports of DM, with follow-up through 1997, compared among women categorized by menstrual cycle length (5 categories). RESULTS: During 564 333 person-years of follow-up, there were 507 cases of type 2 DM. Compared with women with a usual cycle length of 26 to 31 days (referent category) at age 18 to 22 years, the relative risk (RR) of type 2 DM among women with a menstrual cycle length that was 40 days or more or was too irregular to estimate was 2.08 (95% confidence interval [CI], 1.62-2.66), adjusting for body mass index at age 18 years and several other potential confounding variables. The RR of type 2 DM associated with long or highly irregular menstrual cycles was greater in obese women, but was also increased in nonobese women (at body mass indexes at age 18 years of <25, 25-29, and >/=30 kg/m, RRs were 1.67 [95% CI, 1.14-2.45], 1.74 [95% CI, 1.07-2.82], and 3.86 [95% CI, 2.33-6.38], respectively). CONCLUSION: Women with long or highly irregular menstrual cycles have a significantly increased risk for developing type 2 DM that is not completely explained by obesity.

Adult↗
PubMed2001

Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis.

BACKGROUND: Antioxidant vitamins may decrease risk of cancer by limiting oxidative DNA damage leading to cancer initiation. Few prospective studies have assessed relations between antioxidant vitamins and ovarian carcinoma. METHODS: The authors prospectively assessed consumption of vitamins A, C, and E and specific carotenoids, as well as fruit and vegetable intake, in relation to ovarian carcinoma risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin carcinoma. Women reported on known and suspected ovarian carcinoma risk factors including reproductive factors, smoking, and use of vitamin supplements on biennial mailed questionnaires from 1976 to 1996. Food frequency questionnaires were included in 1980, 1984, 1986, and 1990. The authors confirmed 301 incident cases of invasive epithelial ovarian carcinoma during 16 years of dietary follow-up (1980-1996). Pooled logistic regression was used to control for age, oral contraceptive use, body mass index, smoking history, parity, and tubal ligation. RESULTS: The authors observed no association between ovarian carcinoma risk and antioxidant vitamin consumption from foods, or foods and supplements together. The multivariate relative risks (95% confidence intervals [CIs]) for ovarian carcinoma among women in the highest versus lowest quintile of intake were 1.04 (95% CI, 0.72-1.51) for vitamin A from foods and supplements; 1.01 (95% CI, 0.69-1.47) for vitamin C; 0.88 (95% CI, 0.61-1.27) for vitamin E; and 1.10 (95% CI, 0.76-1.59) for beta-carotene. Among users of vitamin supplements, the authors found no evidence of an association between dose or duration of any specific vitamin and ovarian carcinoma risk, although the authors had limited power to assess these relations. No specific fruits or vegetables were associated significantly with ovarian carcinoma risk. The authors found no association between ovarian carcinoma and consumption of total fruits or vegetables, or specific subgroups including cruciferous vegetables, green leafy vegetables, legumes, or citrus fruits. Women who consumed at least 2.5 total servings of fruits and vegetables as adolescents had a 46% reduction in ovarian carcinoma risk (relative risk, 0.54, 95% CI, 0.29-1.03; P value for trend 0.04). CONCLUSIONS: These data do not support an important relation between consumption of antioxidant vitamins from foods or supplements, or intake of fruits and vegetables, and incidence of ovarian carcinoma in this cohort. However, modest associations cannot be excluded, and the authors' finding of an inverse association for total fruit and vegetable intake during adolescence raises the possibility that the pertinent exposure period may be much earlier than formerly anticipated.

Adolescent↗
PubMed2001

Rotating night shifts and risk of breast cancer in women participating in the nurses' health study.

BACKGROUND: Melatonin shows potential oncostatic action, and light exposure during night suppresses melatonin production. There is little information, however, about the direct effect of night work on the risk of cancer. We investigated the effect of night work in breast cancer. METHODS: We examined the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts with at least three nights per month. From June 1988 through May 1998, we documented 2441 incident breast cancer cases. Logistic regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and breast cancer risk factors. All statistical tests were two-sided. RESULTS: We observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR = 1.08 [95% CI = 0.99 to 1.18] and RR = 1.08 [95% CI = 0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR = 1.36; 95% CI = 1.04 to 1.78). The test for trend was statistically significant (P =.02). CONCLUSIONS: Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.

Adult↗
PubMed2001

Predictors of HIV-1 serostatus disclosure: a prospective study among HIV-infected pregnant women in Dar es Salaam, Tanzania.

OBJECTIVES: To examine the socio-demographic and behavioral factors predictive of women's disclosure of an HIV-positive test result in Dar es Salaam, Tanzania. DESIGN: From April 1995 to May 2000, 1078 HIV-positive pregnant women participated in an ongoing randomized trial on micronutrients and HIV-1 vertical transmission and progression. Disclosure to a partner or to a female relative was assessed 2 months after post-test counseling and at 6 monthly follow-up visits. Socio-demographic, health, behavioral and psychological factors were measured at baseline and during follow-up. METHODS: Predictors of time to disclosure of HIV serostatus were determined using Cox proportional hazards regression models. RESULTS: Prevalence of disclosure to a partner ranged from 22% within 2 months to 40% after nearly 4 years. Women were less likely to disclose to their partners if they were cohabiting, had low wage employment, had previously disclosed to a female relative, or reported ever-use of a modern contraceptive method. Women reporting fewer than six lifetime sexual partners or knowing someone with HIV/AIDS were more likely to disclose to their partners. Disclosure to a female relative was predicted by knowing more than two individuals with HIV/AIDS, full economic dependency on their partner, high levels of social support, and prior attendance at a support group meeting. CONCLUSIONS: A substantial proportion of HIV-infected pregnant women never disclosed their result to a partner or a close female relative. Lack of disclosure may have limited their ability to engage in preventive behaviors or to obtain the necessary emotional support for coping with their serostatus or illness.

AIDS Serodiagnosis↗
PubMed2001

Prospective study of recreational physical activity and ovarian cancer.

BACKGROUND: It has been hypothesized that physical activity may reduce the risk of ovarian cancer by decreasing estrogen levels, reducing body fat, and reducing the frequency of ovulation. Epidemiologic studies of this relationship have obtained inconsistent results. The only prospective study to date reported a positive association between frequent vigorous exercise and ovarian cancer risk. We further evaluated this relationship in the Nurses' Health Study cohort. METHODS: Participation in recreational physical activity was assessed by questionnaire in 1980, 1982, 1986, 1988, 1992, and 1994, with questions assessing exercise frequency, duration, and intensity. Results were adjusted for age, parity, oral contraceptive use, tubal ligation, and other risk factors for ovarian cancer. All statistical tests were two-sided. RESULTS: During a 16-year follow-up (from 1980 to 1996), 1.2 million person-years were accrued by 92 825 cohort members, and 377 cases of epithelial ovarian cancer were confirmed. The relative risk (RR) of ovarian cancer for women engaging in recreational physical activity for 7 hours or more per week compared with those reporting less than 1 hour per week was 0.80 (95% confidence interval [CI] = 0.49 to 1.32; P(trend) =.59). When both the frequency and intensity of activity were taken into account, activity level was also not associated with a reduced risk of ovarian cancer. Compared with inactive women, participants reporting high activity in terms of metabolic equivalent task hours (MET hours) were at greater risk of ovarian cancer (RR for 20 to <30 MET hours/week = 1.84 [95% CI = 1.12 to 3.02]; RR for >30 MET hours/week = 1.27 [95% CI = 0.75 to 2.14]). CONCLUSIONS: Overall, results did not suggest an inverse association between recreational physical activity and ovarian cancer. The possibility of a modest increase in risk with frequent vigorous activity requires further investigation.

Adult↗
PubMed2001

Types of dietary fat and breast cancer: a pooled analysis of cohort studies.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

Breast Neoplasms↗
PubMed2001

Vitamin supplement use and the risk of non-Hodgkin's lymphoma among women and men.

The authors examined use of individual supplements of vitamins A, C, and E only and multivitamins in relation to risk of non-Hodgkin's lymphoma in prospective cohorts of 88,410 women in the Nurses' Health Study (1980-1996), with 261 incident cases during 16 years of follow-up, and of 47,336 men in the Health Professionals Follow-Up Study (1986-1996), with 111 incident cases during 10 years of follow-up. Multivitamin use was associated with a higher risk of non-Hodgkin's lymphoma among women but not among men; the multivariate relative risks for long-term duration (10 or more years) were 1.48 (95% confidence interval (CI): 1.01, 2.16) for women and 0.85 (95% CI: 0.45, 1.58) for men. The pooled multivariate relative risk from the two cohorts was 1.18 (95% CI: 0.70, 2.02). Use of individual supplements of vitamins A, C, and E only was not associated with risk among men. An increased risk associated with the use of individual supplements of vitamins A, C, and E only among women appeared to be secondary to the use of multivitamins by the same persons. Because an elevated risk among multivitamin users was not observed consistently in the two cohorts and the pooled data were not significant, the elevated risk among women may be the result of chance.

Adult↗
PubMed2001

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.

BACKGROUND: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. METHODS: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. RESULTS: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. CONCLUSIONS: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.

Body Weight↗
PubMed2001

A polymorphism in CYP17 and endometrial cancer risk.

Among women, the A2 allele of CYP17 has been associated with elevated levels of endogenous steroid hormones; however, it does not seem to be a strong independent risk factor for breast cancer. We assessed the association between the A2 allele of CYP17 and invasive endometrial cancer risk in a case-control study nested within the Nurses' Health Study cohort (cases: n = 184; controls: n = 554). We also evaluated whether endometrial cancer risk associated with CYP17 genotype was modified by established endometrial cancer risk factors. In addition, we further examined the relationship between CYP17 genotype and endogenous plasma steroid hormone levels among postmenopausal controls not using hormone replacement therapy (HRT). Women with the A2 allele of CYP17 were at decreased risk of endometrial cancer (A1/A1 genotype (reference); A1/A2 genotype: odds ratio, 0.89; 95% confidence interval, 0.62-1.27; A2/A2 genotype: odds ratio, 0.43; 95% confidence interval, 0.23-0.80; P trend, 0.02). We also observed the inverse association between the A2 allele and endometrial cancer risk to be stronger among women with a first-degree family history of endometrial and/or colorectal cancer (P for interaction, 0.05). Among 165 controls, we did not observe women with the A2 allele to have significantly elevated levels of any steroid hormone fraction. When these women were combined and analyzed with those women on whom we had previously examined the relationship between CYP17 genotype and circulating hormone levels (total n = 469), only modest associations were observed for the A2/A2 genotype and steroid hormone fractions estrone (versus A1/A1 genotype: +10.9%; P = 0.05) and estradiol (+8.5%; P = 0.17). These data suggest that the A2 allele of CYP17 decreases endometrial cancer risk, but has only weak effects on endogenous estrogen levels among postmenopausal women.

Adult↗