Biomedical subjects

G A Colditz

Publications and source records attributed to G A Colditz.

At least 73 records · Page 4Linked to original sources

PubMed2001

Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies.

OBJECTIVE: The diagnostic value of tests for antimyeloperoxidase antibodies (anti-MPO) for systemic vasculitis is less established than that for cytoplasmic antineutrophil cytoplasmic antibody (cANCA)/antiproteinase 3 antibodies (anti-PR3). Controversy exists regarding the optimal utilization of indirect immunofluorescence (IIF) ANCA testing versus antigen-specific ANCA testing. To summarize the pertinent data, we conducted a metaanalysis examining the diagnostic value of ANCA testing systems that include assays for anti-MPO. METHODS: We performed a structured Medline search and reference list review. Target articles in the search strategy were those reporting the diagnostic value of immunoassays for anti-MPO for the spectrum of systemic necrotizing vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, the Churg-Strauss syndrome, and isolated pauci-immune necrotizing or crescentic glomerulonephritis, regardless of other types of ANCA tests. Inclusion criteria required specification of a consecutive or random patient selection method and the use of acceptable criteria for the diagnosis of vasculitis exclusive of ANCA test results. Weighted pooled summary estimates of sensitivity and specificity were calculated for anti-MPO alone, anti-MPO + perinuclear ANCA (pANCA), and anti-MPO/pANCA + anti-PR3/cANCA. RESULTS: Of 457 articles reviewed, only 7 met the selection criteria. Summary estimates of sensitivity and specificity (against disease controls only) of assays for anti-MPO for the diagnosis of systemic necrotizing vasculitides were 37.1% (confidence interval 26.6% to 47.6%) and 96.3% (CI 94.1% to 98.5%), respectively. When the pANCA pattern by IIF was combined with anti-MPO testing, the specificity improved to 99.4%, with a lower sensitivity, 31.5%. The combined ANCA testing system (anti-PR3/cANCA + anti-MPO/pANCA) increased the sensitivity to 85.5% with a specificity of 98.6%. CONCLUSION: These results suggest that while anti-MPO is relatively specific for the diagnosis of systemic vasculitis, the combination system of immunoassays for anti-MPO and IIF for pANCA is highly specific and both tests should be used together given the high diagnostic precision required for these conditions. Because patients with ANCA associated vasculitis have either anti-MPO with pANCA or anti-PR3 with cANCA, and rarely both, a combined ANCA testing system including anti-PR3/cANCA and anti-MPO/pANCA is recommended to optimize the diagnostic performance of ANCA testing.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2000

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.

BACKGROUND: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progestin in this regard. OBJECTIVE: To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. DESIGN: Prospective, observational cohort study. SETTING: Nurses' Health Study, with follow-up from 1976 to 1996. PATIENTS: 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. MEASUREMENTS: Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. RESULTS: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). CONCLUSIONS: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.

Adult↗

PubMed2000

The persistent impact of breast carcinoma on functional health status: prospective evidence from the Nurses' Health Study.

BACKGROUND: Although physical and emotional function after the diagnosis of breast carcinoma have been described in clinic populations, to the authors' knowledge no previous study has measured change from the preillness level of functional health status in community-dwelling women. METHODS: The authors conducted a 4-year (1992-96) prospective study of functional recovery after breast carcinoma in a large sample of women, aged 54-73 years. They collected multidimensional measures of self-reported functional health status in 1992, before diagnosis of breast carcinoma, and again in 1996, to examine the risk of decline associated with incident breast carcinoma. RESULTS: After adjustment for age, baseline functional health status, and multiple covariates, women who developed incident breast carcinoma were more likely to have experienced reduced physical function, role function, vitality, and social function and increased bodily pain compared with women who remained free of breast carcinoma. Risk of decline was attenuated with increasing time since diagnosis. Risk of decline in physical function was evident across all stages of breast carcinoma, even after adjustment for women undergoing treatment for persistent or recurrent disease. We found evidence that the risk of decline among breast carcinoma cases compared with healthy women was largest among those who were most socially isolated. CONCLUSIONS: Breast carcinoma results in persistent declines in multiple dimensions of functional health status. These prospective data suggest that previous studies reporting no difference in physical function among breast carcinoma cases compared with disease free women underestimated the deleterious effect of the disease on function. Socially isolated women are an especially vulnerable group.

Adult↗

PubMed2000

Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk.

BACKGROUND: A history of proliferative benign breast disease has been shown to increase the risk of developing breast carcinoma, but, to the authors' knowledge, how postmenopausal exogenous female hormone use, in general, has affected breast carcinoma risk among women with a history of proliferative breast disease with or without atypia has not been well established. METHODS: In the current case-control study, nested within the Nurses' Health Study, benign breast biopsy slides of 133 postmenopausal breast carcinoma cases and 610 controls with a history of benign breast disease, were reviewed. Reviewers had no knowledge of case status. RESULTS: Women with proliferative disease without atypia had a relative risk for postmenopausal breast carcinoma of 1.8 (95%, confidence interval [CI]: 1.1 to 2.8), and women with atypical hyperplasia had a relative risk of 3.6 (95%, CI: 2.0 to 6.4) compared with women who had nonproliferative benign histology. Neither current postmenopausal use of exogenous female hormones nor long term use for 5 or more years further increased the risk of breast carcinoma in the study population beyond that already associated with their benign histology. CONCLUSIONS: Women who had proliferative benign breast disease, with or without atypia, were at moderately to substantially increased risk of developing postmenopausal breast carcinoma compared with women who had nonproliferative benign conditions. In the current study, postmenopausal exogenous female hormone use in general did not further increase the breast carcinoma risk for women with proliferative benign breast disease. However, the analysis did not exclude the possibility of increased risk with a particular hormone combination or dosage.

Biopsy↗

PubMed2000

Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study.

Because of the temporal relations between reproductive risk factors and incidence of breast cancer, the authors developed a nonlinear Poisson regression that accounts for time and summarizes risk to age 70 years. Reproductive risk factors, benign breast disease, use of postmenopausal hormones, weight, and alcohol intake were evaluated as risk factors. Among 58,520 women aged 30-55 years in 1980, followed through June 1, 1994, 1,761 incident invasive breast cancer cases were identified. All risks are multivariate adjusted. History of benign breast disease is associated with a 57% increase (95% confidence interval (CI): 43%, 73%) in cumulative risk of breast cancer by age 70 years. Use of unopposed postmenopausal estrogen from ages 50-60 years increases risk of breast cancer to age 70 by 23% (95% CI: 6%, 42%) compared with a woman who never uses hormones. Ten years of use of estrogen plus progestin increases risk to age 70 years by 67% (95% CI: 18%, 136%). Compared with never drinking alcohol, one drink per day from age 18 years increases risk to age 70 by 7% (95% CI: 0%, 13%). Use of unopposed postmenopausal hormones for 10 years significantly increases the risk of breast cancer, and the addition of progestin further increases the risk.

Adult↗

PubMed2000

Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women.

BACKGROUND: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. beta-Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. METHODS: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses' Health Study and 47 778 men in the Health Professionals' Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. RESULTS: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59-1.06) among the women and 1.12 (95% CI = 0.74-1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35-1.12 in the highest tertile). CONCLUSION: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked.

Adult↗

PubMed2000

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.

Adult↗

PubMed2000

Dietary fat intake and endogenous sex steroid hormone levels in postmenopausal women.

PURPOSE: To examine the relationship between plasma levels of reproductive sex steroid hormones in postmenopausal women and their reported fat intake. METHODS: We measured plasma sex steroid hormones levels in plasma collected in 1989 and 1990 from 381 healthy postmenopausal women. For each woman, we measured fat intake in 1986 and 1990 by a food-frequency questionnaire. The cross-sectional associations between the percentage of energy from total and specific types of dietary fat intake and plasma hormone levels were assessed by linear regression, controlling for energy intake, obesity, and protein intake. RESULTS: The plasma estradiol level was 4.3% lower (95% confidence limits, -8.3%, -0.2%) for a substitution of 5% of energy from fat intake for an equivalent amount of energy from carbohydrate when adjusted for obesity and other covariates. Estradiol was also inversely associated with all other fat types except trans fat; the inverse associations with vegetable fat and marine omega-3 fats were statistically significant. CONCLUSION: We observed an inverse association between total fat intake averaged over 4 to 5 years and estradiol levels. This result is inconsistent with the hypothesis that fat intake predisposes to breast cancer risk by raising endogenous estrogen levels.

Adult↗

PubMed2000

Cost-effectiveness of screening for colorectal cancer in the general population.

CONTEXT: A recent expert panel recommended that persons at average risk of colorectal cancer (CRC) begin screening for CRC at age 50 years using 1 of several strategies. However, many aspects of different CRC screening strategies remain uncertain. OBJECTIVE: To assess the consequences, costs, and cost-effectiveness of CRC screening in average-risk individuals. DESIGN: Cost-effectiveness analysis from a societal perspective using a Markov model. SUBJECTS: Hypothetical subjects representative of the 50-year-old US population at average risk for CRC. SETTING: Simulated clinical practice in the United States. MAIN OUTCOME MEASURES: Discounted lifetime costs, life expectancy, and incremental cost-effectiveness (CE) ratio, compared used 22 different CRC screening strategies, including those recommended by the expert panel. RESULTS: In 1 base-case analysis, compliance was assumed to be 60% with the initial screen and 80% with follow-up or surveillance colonoscopy. The most effective strategy for white men was annual rehydrated fecal occult blood testing (FOBT) plus sigmoidoscopy (followed by colonoscopy if either a low- or high-risk polyp was found) every 5 years from age 50 to 85 years, which resulted in a 60% reduction in cancer incidence and an 80% reduction in CRC mortality compared with no screening, and an incremental CE ratio of $92,900 per year of life gained compared with annual unrehydrated FOBT plus sigmoidoscopy every 5 years. In a base-case analysis in which compliance with screening and follow-up is assumed to be 100%, screening more often than every 10 years was prohibitively expensive; annual rehydrated FOBT plus sigmoidoscopy every 5 years had an incremental CE ratio of $489,900 per life-year gained compared with the same strategy every 10 years. Other strategies recommended by the expert panel were either less effective or cost more per year of life gained than the alternatives. Colonoscopy every 10 years was less effective than the combination of annual FOBT plus sigmoidoscopy every 5 years. However, a single colonoscopy at age 55 years achieves nearly half of the reduction in CRC mortality obtainable with colonoscopy every 10 years. Because of increased life expectancy among white women and increased cancer mortality among blacks, CRC screening was even more cost-effective in these groups than in white men. CONCLUSIONS: Screening for CRC, even in the setting of imperfect compliance, significantly reduces CRC mortality at costs comparable to other cancer screening procedures. However, compliance rates significantly affect the incremental CE ratios. In this model of CRC, 60% compliance with an every 5-year schedule of screening was roughly equivalent to 100% compliance with an every 10-year schedule. Mathematical modeling used to inform clinical guidelines needs to take into account expected compliance rates. JAMA. 2000;284:1954-1961.

Colonic Polyps↗

PubMed2000

Relation of childhood diet and body size to menarche and adolescent growth in girls.

Adolescent growth and development may be affected by factors such as dietary intake and body size from much earlier in childhood. In a longitudinal study of 67 Caucasian girls in Boston, Massachusetts, data were collected prospectively from birth during the 1930s and 1940s. Heights and weights were measured semiannually, and dietary history interviews were conducted with mothers. Stepwise linear regression methods were used to seek factors which best predicted age at menarche, adolescent peak height growth velocity, and the age at which peak growth velocity occurred. Girls who consumed more (energy-adjusted) animal protein and less vegetable protein at ages 3-5 years had earlier menarche, and girls aged 1-2 years with higher dietary fat intakes and girls aged 6-8 years with higher animal protein intakes became adolescents with earlier peak growth. Controlling for body size, girls who consumed more calories and animal protein 2 years before peak growth had higher peak growth velocity. These findings may have implications regarding adult diseases whose risks are associated with adolescent growth and development factors.

Adolescent↗

PubMed2000

Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women.

BACKGROUND: Previous studies have found concurrent declines in blood pressure, serum cholesterol levels, and the incidence of and mortality from coronary disease. However, the effects of changes in diet and lifestyle on trends in coronary disease are largely unknown. METHODS: We followed 85,941 women who were 34 to 59 years old and had no previously diagnosed cardiovascular disease or cancer from 1980 to 1994 in the Nurses' Health Study. Diet and lifestyle variables were assessed at base line and updated during follow-up. RESULTS: After adjustment for the effect of age, the incidence of coronary disease declined by 31 percent from the two-year period 1980-1982 to the two-year period 1992-1994. From 1980 to 1992, the proportion of participants currently smoking declined by 41 percent, the proportion of postmenopausal women using hormone therapy increased by 175 percent, and the prevalence of overweight, defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or more, increased by 38 percent. During the study period, diet improved substantially. Statistically, changes in these variables--when considered simultaneously--explained a 21 percent decline in the incidence of coronary disease, representing 68 percent of the overall decline from 1980-1982 to 1992-1994. Taken individually, the reduction in smoking explained a 13 percent decline in the incidence of coronary disease; improvement in diet explained a 16 percent decline; and increase in postmenopausal hormone use explained a 9 percent decline. On the other hand, the increase in body-mass index explained an 8 percent increase in the incidence of coronary disease. CONCLUSIONS: Reduction in smoking, improvement in diet, and an increase in postmenopausal hormone use accounted for much of the decline in the incidence of coronary disease in this group of women. An increasing prevalence of obesity, however, appears to have slowed the decline in the incidence of coronary disease.

Adult↗

PubMed2000

Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus.

BACKGROUND: Moderate alcohol consumption is associated with reduced risk for coronary heart disease (CHD) in generally healthy populations. We assessed prospectively the association between moderate alcohol intake and CHD risk in women with type 2 diabetes mellitus, a group at high risk for cardiovascular disease. METHODS AND RESULTS: We studied women in the Nurses' Health Study who reported a diagnosis of diabetes mellitus at >/=30 years of age. During 39 092 person-years of follow-up from 1980 to 1994, there were 295 CHD events documented among this population, including 194 cases of nonfatal myocardial infarction and 101 cases of fatal CHD. Odds ratios derived from logistic regression were used to estimate relative risks (RRs) for CHD as a function of usual alcohol intake, with adjustment for potential confounders. Compared with diabetic women reporting no alcohol intake, the age-adjusted RR for nonfatal or fatal CHD among diabetic women reporting usual intake of 0.1 to 4.9 g (<0.5 drinks) of alcohol daily was 0.74 (95% CI 0.56 to 0.98), and among those reporting usual intake >/=5 g/d, it was 0.48 (95% CI 0.32 to 0.72) (P for trend <0.0001). Inverse associations between alcohol intake and CHD risk remained significant in multivariate analysis adjusting for several other coronary risk factors (0.1 to 4. 9 g/d: RR 0.72 [95% CI 0.54 to 0.96]; >/=5 g/d: RR 0.45 [0.29 to 0.68]). CONCLUSIONS: Although potential risks of alcohol consumption must be considered, these data suggest that moderate alcohol consumption is associated with reduced CHD risk in women with diabetes and should not be routinely discouraged.

Adult↗

PubMed2000

A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk.

The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case-control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA(7-13)). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)(10) repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)(12) allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0-3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (-16.4%, p = 0.02), estrone (-6.1%, p = 0.22) and estradiol (-9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (-10.5%, p = 0.08) compared to non-carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose-specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution.

Alleles↗

PubMed2000

Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density.

Insulin-like growth factors (IGFs) and insulin-like growth factor-binding proteins (IGFBPs) play a role in the normal development of breast tissue and possibly in the etiology of breast cancer. Breast density is one of the strongest predictors of breast cancer. In a cross-sectional analysis within the Nurses' Health Study, we compared the associations of plasma levels of endogenous IGF-I and IGFBP-3 with breast density in 65 premenopausal and 192 postmenopausal women. The digitized film screen mammograms were evaluated by the computer-assisted Toronto method, in which visually selected gray-scale cut points are used to assess breast density. Generalized linear models and Spearman's partial correlation coefficients described the associations between breast density and IGF-I, IGFBP-3, and the IGF-I:IGFBP-3 ratio. Premenopausal breast density was positively correlated with IGF-I and inversely correlated with IGFBP-3; the association was strongest for the IGF-I:IGFBP-3 ratio and breast density (r = 0.39; P = 0.004). In contrast, the correlation between breast density and the IGF-I:IGFBP-3 ratio among postmenopausal women was -0.02 (P = 0.83). The associations of IGF-I:IGFBP-3 ratio with breast density differed significantly between premenopausal and postmenopausal women (P = 0.01). Mammographic density is positively associated with plasma IGF-I levels and inversely associated with plasma IGFBP-3 levels among premenopausal women, but not among postmenopausal women. These results are consistent with previous studies that showed a positive association between a higher IGF-I:IGFBP-3 ratio and subsequent risk of breast cancer only among premenopausal women. The findings raise the possibility that premenopausal levels of IGF-I and IGFBP-3 could be in the etiological pathway that relates higher breast density with increased breast cancer risk.

Aged↗

PubMed2000

Polymorphic repeat in AIB1 does not alter breast cancer risk.

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

Adult↗

PubMed2000

Physical activity and risk of stroke in women.

CONTEXT: Persuasive evidence has demonstrated that increased physical activity is associated with substantial reduction in risk of coronary heart disease. However, the role of physical activity in the prevention of stroke is less well established. OBJECTIVE: To examine the association between physical activity and risk of total stroke and stroke subtypes in women. DESIGN AND SETTING: The Nurses' Health Study, a prospective cohort study of subjects residing in 11 US states. SUBJECTS: A total of 72,488 female nurses aged 40 to 65 years who did not have diagnosed cardiovascular disease or cancer at baseline in 1986 and who completed detailed physical activity questionnaires in 1986, 1988, and 1992. MAIN OUTCOME MEASURE: Incident stroke occurring between baseline and June 1, 1994, compared among quintiles of physical activity level as measured by metabolic equivalent tasks (METs) in hours per week. RESULTS: During 8 years (560,087 person-years) of follow-up, we documented 407 incident cases of stroke (258 ischemic strokes, 67 subarachnoid hemorrhages, 42 intracerebral hemorrhages, and 40 strokes of unknown type). In multivariate analyses controlling for age, body mass index, history of hypertension, and other covariates, increasing physical activity was strongly inversely associated with risk of total stroke. Relative risks (RRs) in the lowest to highest MET quintiles were 1. 00, 0.98, 0.82, 0.74, and 0.66 (P for trend=.005). The inverse gradient was seen primarily for ischemic stroke (RRs across increasing MET quintiles, 1.00, 0.87, 0.83, 0.76, and 0.52; P for trend=.003). Physical activity was not significantly associated with subarachnoid hemorrhage or intracerebral hemorrhage. After multivariate adjustment, walking was associated with reduced risk of total stroke (RRs across increasing walking MET quintiles, 1.00, 0. 76, 0.78, 0.70, and 0.66; P for trend=.01) and ischemic stroke (RRs across increasing walking MET quintiles, 1.00, 0.77, 0.75, 0.69, and 0.60; P for trend=.02). Brisk or striding walking pace was associated with lower risk of total and ischemic stroke compared with average or casual pace. CONCLUSION: These data indicate that physical activity, including moderate-intensity exercise such as walking, is associated with substantial reduction in risk of total and ischemic stroke in a dose-response manner. JAMA. 2000.

Adult↗

PubMed2000

Prospective study of bowel movement, laxative use, and risk of colorectal cancer among women.

The authors prospectively examined the association between bowel movement frequency, laxative use, and the risk of colorectal cancer in 84,577 women of the Nurses' Health Study living in the United States, 36-61 years of age and free of cancer in 1982. Between 1984 and 1996, 611 incident cases of colorectal cancer were documented. After controlling for age, body mass index, fiber intake, postmenopausal status and hormone use, physical activity, and use of laxatives, the relative risks associated with having bowel movements every third day or less, compared with those with bowel movements once daily, were 0.94 (95% confidence interval (CI): 0.69, 1.28) for colorectal cancer, 0.88 (95% CI: 0.62, 1.26) for colon cancer, and 1.18 (95% CI: 0.63, 2.20) for rectal cancer. Compared with women who never used laxatives, the multivariate relative risks associated with weekly to daily laxative use were 1.00 (95% CI: 0.72, 1.40) for colorectal cancer, 1.09 (95% CI: 0.76, 1.57) for colon cancer, and 0.68 (95% CI: 0.29, 1.57) for rectal cancer. These findings do not support an association between infrequent bowel movement, laxative use, and risk of colorectal cancer and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict colorectal cancer risk.

Aged↗

PubMed2000

Bias in breast cancer analyses due to error in age at menopause.

With the use of data from the Nurses' Health Study, the authors confirm the recent argument by Pike et al. (Am J Epidemiol 1998;147:718-21) that various ways of assigning ages at menopause to women with simple hysterectomy produce relative risks for the effect of hormone replacement therapy (HRT) that are biased downward. Different methods of including women with simple hysterectomy consistently produced relative risks for the association between a 1-year increase in duration of HRT use and breast cancer that were underestimates compared with the relative risk obtained when these women were excluded from analysis. The authors used longitudinal data on recalled age at menopause to demonstrate another source of error related to age at menopause: error in recall of age at menopause that increases with time since menopause.

Adult↗