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Biomedical subjects

G A Colditz

Publications and source records attributed to G A Colditz.

At least 127 records · Page 7Linked to original sources
PubMed1999

A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.

BACKGROUND: The role of walking, as compared with vigorous exercise, in the prevention of coronary heart disease remains controversial, and data for women on this topic are sparse. METHODS: We prospectively examined the associations between the score for total physical activity, walking, and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986. Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed questionnaires about physical activity. During eight years of follow-up, we documented 645 incident coronary events (nonfatal myocardial infarction or death from coronary disease). RESULTS: There was a strong, graded inverse association between physical activity and the risk of coronary events. As compared with women in the lowest quintile group for energy expenditure (expressed as the metabolic-equivalent [MET] score), women in increasing quintile groups had age-adjusted relative risks of 0.77, 0.65, 0.54, and 0.46 for coronary events (P for trend <0.001). In multivariate analyses, the inverse gradient remained strong (relative risks, 0.88, 0.81, 0.74, and 0.66 for women in increasing quintile groups as compared with those in the lowest quintile group; P for trend=0.002). Walking was inversely associated with the risk of coronary events; women in the highest quintile group for walking, who walked the equivalent of three or more hours per week at a brisk pace, had a multivariate relative risk of 0.65 (95 percent confidence interval, 0.47 to 0.91) as compared with women who walked infrequently. Regular vigorous exercise (> or =6 MET) was associated with similar risk reductions (30 to 40 percent). Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary. CONCLUSIONS: These prospective data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women.

Adult↗
PubMed1999

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.

CONTEXT: Coffee has several metabolic effects that could reduce the risk of gallstone formation. OBJECTIVE: To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. DESIGN AND SETTING: The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996. PARTICIPANTS: A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease. MAIN OUTCOME MEASURES: Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy. RESULTS: During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk. CONCLUSIONS: In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.

Adult↗
PubMed1999

Long-term intake of dietary fiber and decreased risk of coronary heart disease among women.

CONTEXT: Epidemiological studies of men suggest that dietary fiber intake protects against coronary heart disease (CHD), but data on this association in women are sparse. OBJECTIVE: To examine the association between long-term intake of total dietary fiber as well as fiber from different sources and risk of CHD in women. DESIGN AND SETTING: The Nurses' Health Study, a large, prospective cohort study of US women followed up for 10 years from 1984. Dietary data were collected in 1984, 1986, and 1990, using a validated semiquantitative food frequency questionnaire. PARTICIPANTS: A total of 68782 women aged 37 to 64 years without previously diagnosed angina, myocardial infarction (MI), stroke, cancer, hypercholesterolemia, or diabetes at baseline. MAIN OUTCOME MEASURE: Incidence of acute MI or death due to CHD by amount of fiber intake. RESULTS: Response rate averaged 80% to 90% during the 10-year follow-up. We documented 591 major CHD events (429 nonfatal MIs and 162 CHD deaths). The age-adjusted relative risk (RR) for major CHD events was 0.53 (95% confidence interval [CI], 0.40-0.69) for women in the highest quintile of total dietary fiber intake (median, 22.9 g/d) compared with women in the lowest quintile (median, 11.5 g/d). After controlling for age, cardiovascular risk factors, dietary factors, and multivitamin supplement use, the RR was 0.77 (95% CI, 0.57-1.04). For a 10-g/d increase in total fiber intake (the difference between the lowest and highest quintiles), the multivariate RR of total CHD events was 0.81 (95% CI, 0.66-0.99). Among different sources of dietary fiber (eg, cereal, vegetables, fruit), only cereal fiber was strongly associated with a reduced risk of CHD (multivariate RR, 0.63; 95% CI, 0.49-0.81 for each 5-g/d increase in cereal fiber). CONCLUSIONS: Our findings in women support the hypothesis that higher fiber intake, particularly from cereal sources, reduces the risk of CHD.

Adult↗
PubMed1999

Adolescence and breast carcinoma risk.

BACKGROUND: Breast carcinoma risk may be modified by early life factors, including physical growth and development, diet, and life-style factors of preadolescence and adolescence, as well as genetic factors. METHODS: The authors tested their hypothesis that adolescent growth and development are related to breast carcinoma incidence by evaluating 65,140 women who participated in the Nurses' Health Study. During 16 years of follow-up, 806 women were diagnosed with breast carcinoma prior to menopause, and another 1485 were diagnosed after menopause. Because adolescent growth was not directly observed in this cohort, the peak height growth velocity for each participant was estimated by using a model from another longitudinal study. Finally, Cox proportional hazards regression models were used to study associations between breast carcinoma incidence and adolescent factors in the Nurses' Health Study. RESULTS: Later menarche (relative risk [RR] = 0.52 for > or =15 vs. < or =11 years) and more body fatness at age 10 years (RR = 0.60 for fattest vs. leanest) were associated with a decreased risk of premenopausal breast carcinoma. The risk of postmenopausal breast carcinoma was lower for girls with later menarche (RR = 0.80), more body fat at age 10 years (RR = 0.72), and shorter adult height (RR = 1.29 for > or =67 vs. < or =62 inches). Higher peak height growth velocity, derived from these 3 variables, was associated with increased risk of both premenopausal (RR = 1.31 for highest vs. lowest quintile) and postmenopausal (RR = 1.40) breast carcinoma. These analyses controlled for birth cohort, other possible risk factors from the adolescent period, and family history. These associations persisted after controlling for age at the birth of a first child, parity, adult adiposity, and age at menopause. Post-hoc analyses suggested that, although childhood body fatness was associated with lower risk, increasing body fatness between ages 10 and 20 years was not protective against either premenopausal or postmenopausal breast carcinoma. CONCLUSIONS: Earlier menarche, extremely lean body mass at age 10 years, and taller adult height were predictive of elevated breast carcinoma risk. The same three factors were also predictive of higher peak growth velocities during adolescence, lending credence to the hypothesis that more rapid adolescent growth may increase the risk of breast carcinoma development.

Adolescent↗
PubMed1999

Age at natural menopause and risk of cardiovascular disease.

BACKGROUND: Early natural menopause has been postulated to increase the risk of cardiovascular disease. OBJECTIVE: To examine the relation of age at natural menopause with risk of coronary heart disease (CHD) and stroke in the Nurses' Health Study. METHODS: Analysis was restricted to 35 616 naturally postmenopausal women who never used estrogen replacement therapy and with no diagnosed cardiovascular disease at baseline, followed up from 1976 to 1994. Information on menopausal status, age at menopause, and other risk factors was obtained in 1976 and updated every 2 years by mailed questionnaires. RESULTS: During 354326 person-years of follow-up, we documented 757 incident cases of CHD and 350 incident cases of stroke. After adjusting for age, smoking status, and other cardiovascular risk factors, the relative risks (RRs) across categories of age at natural menopause (<40, 40-44, 45-49, 50-54, and > or = 55 years) were 1.53, 1.42, 1.10, 1.00 (reference), and 0.95, respectively; the RR for each 1-year decrease in age at natural menopause was 1.03 (95% confidence interval, 1.01-1.05). Elevated risk with younger age at menopause was observed among current smokers (RR, 1.04 [95% CI, 1.01-1.07] for each 1-year decrease in age at natural menopause) but not among never smokers (RR, 1.00; 95% CI, 0.96-1.04). Age at natural menopause was not significantly associated with ischemic stroke (RR, 1.01; 95% CI, 0.97-1.04) or hemorrhagic stroke (RR, 1.03; 95% CI, 0.97-1.10). CONCLUSIONS: We observed an overall significant association between younger age at menopause and higher risk of CHD among women who experienced natural menopause and never used hormone therapy. This increased risk was observed among current smokers but not among never smokers. The apparent elevated risk of CHD with decreased age at natural menopause among smokers might reflect residual confounding by smoking.

Age of Onset↗
PubMed1999

A prospective study of folate intake and the risk of breast cancer.

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.

Adult↗
PubMed1999

A prospective study of egg consumption and risk of cardiovascular disease in men and women.

CONTEXT: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. OBJECTIVE: To examine the association between egg consumption and risk of CHD and stroke in men and women. DESIGN AND SETTING: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). PARTICIPANTS: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire. RESULTS: We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]). CONCLUSIONS: These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.

Adult↗
PubMed1999

Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women.

BACKGROUND: In animal studies, prolactin has been found to be important for mammary epithelial development and its administration has been shown consistently to increase the rate of mammary tumor formation. Previous epidemiologic studies of prolactin and breast cancer risk in postmenopausal women have been limited in size, and the results have been inconsistent. We conducted a nested case-control study within the prospective Nurses' Health Study cohort to better determine the relationship between plasma prolactin levels and postmenopausal breast cancer risk. METHODS: Blood samples were collected from cohort members during the period from 1989 through 1990. Prolactin levels were measured by use of a microparticle enzyme immunoassay. Included in this analysis were 306 postmenopausal women who were diagnosed with breast cancer after blood donation but before June 1994. One or two postmenopausal control subjects were matched per case subject on the basis of age, postmenopausal hormone use, and time of day and month of blood collection; the study included a total of 448 control subjects. RESULTS: In conditional logistic regression analyses, a significant positive association was observed between plasma level of prolactin and postmenopausal breast cancer risk (highest versus lowest quartile, multivariate relative risk = 2.03; 95% confidence interval = 1.24-3.31; two-sided P for trend = .01). The relationship was independent of plasma sex steroid hormone levels and was similar after excluding case subjects diagnosed in the first 2 years after blood collection. CONCLUSIONS: These prospective data suggest that higher plasma prolactin levels are associated with an increased risk of breast cancer in postmenopausal women.

Adult↗
PubMed1999

Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women.

BACKGROUND: The remarkable similarity of lifestyle and environmental risk factors for type 2 (non-insulin-dependent) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer. We prospectively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976. METHODS: The women, who were enrolled in the Nurses' Health Study, were assessed for history of diabetes at baseline and during follow-up by use of biennial questionnaires. Self-reported diabetes was validated by information obtained from a supplemental questionnaire on symptoms and treatment and was confirmed by medical record review in a sample of the participants. Incident cases of colorectal cancer were ascertained through medical record review. All reported P values are two-sided. RESULTS: During 18 years of follow-up (201061 person-years), we documented 892 new cases of colorectal cancer. After adjustment for age, body mass index (weight in kg/height in m2), physical activity, and other covariates, relative risks (RRs) were 1.43 (95% confidence interval [CI] = 1.10-1.87; P = .009) for colorectal cancer, 1.49 (95% CI = 1.09-2.06; P = .01) for colon cancer, 1.11 (95% CI = 0.56-2.21; P = .76) for rectal cancer, 1.56 (95% CI = 1.07-2.28; P = .02) for advanced colorectal cancer, and 2.39 (95% CI = 1.46-3.92; P = .0005) for fatal colorectal cancer. CONCLUSION: Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women.

Adult↗
PubMed1999

Dietary carotenoids and vitamins A, C, and E and risk of breast cancer.

BACKGROUND: Data on intake of specific carotenoids and breast cancer risk are limited. Furthermore, studies of vitamins A, C, and E in relation to breast cancer risk are inconclusive. We have conducted a large, prospective study to evaluate long-term intakes of these nutrients and breast cancer risk. METHODS: We examined, by use of multivariate analysis, associations between intakes of specific carotenoids, vitamins A, C, and E , consumption of fruits and vegetables, and breast cancer risk in a cohort of 83234 women (aged 33-60 years in 1980) who were participating in the Nurses' Health Study. Through 1994, we identified 2697 incident cases of invasive breast cancer (784 premenopausal and 1913 postmenopausal). RESULTS: Intakes of beta-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely associated with breast cancer risk in premenopausal women. Strong inverse associations were found for increasing quintiles of alpha-carotene, beta-carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with a positive family history of breast cancer. An inverse association was also found for increasing quintiles of beta-carotene among premenopausal women who consumed 15 g or more of alcohol per day. Premenopausal women who consumed five or more servings per day of fruits and vegetables had modestly lower risk of breast cancer than those who had less than two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] = 0.58-1.02); this association was stronger among premenopausal women who had a positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04). CONCLUSIONS: Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.

Adult↗
PubMed1999

Long-term weight patterns and risk for cholecystectomy in women.

BACKGROUND: Obesity and rapid weight loss in obese persons are known risk factors for gallstones. However, the effect of intentional, long-term, moderate weight changes on the risk for gallstones is unclear. OBJECTIVE: To study long-term weight patterns in a cohort of women and to examine the relation between weight pattern and risk for cholecystectomy. DESIGN: Prospective cohort study. SETTING: 11 U.S. states. PARTICIPANTS: 47,153 female registered nurses who did not undergo cholecystectomy before 1988. MEASUREMENTS: Cholecystectomy between 1988 and 1994 (ascertained by patient self-report). RESULTS: During the exposure period (1972 to 1988), there was evidence of substantial variation in weight due to intentional weight loss during adulthood. Among cohort patients, 54.9% reported weight cycling with at least one episode of intentional weight loss associated with regain. Of the total cohort, 20.1% were light cyclers (5 to 9 lb of weight loss and gain), 18.8% were moderate cyclers (10 to 19 lb of weight loss and gain), and 16.0% were severe cyclers (> or = 20 lb of weight loss and gain). Net weight gain without cycling occurred in 29.3% of women; net weight loss without cycling was the least common pattern (4.6%). Only 11.1% of the cohort maintained weight within 5 lb over the 16-year period. In the study, 1751 women had undergone cholecystectomy between 1988 and 1994. Compared with weight maintainers, the relative risk for cholecystectomy (adjusted for body mass index, age, alcohol intake, fat intake, and smoking) was 1.20 (95% CI, 0.96 to 1.50) among light cyclers, 1.31 among moderate cyclers (CI, 1.05 to 1.64), and 1.68 among severe cyclers (CI, 1.34 to 2.10). CONCLUSION: Weight cycling was highly prevalent in this large cohort of middle-aged women. The risk for cholecystectomy associated with weight cycling was substantial, independent of attained relative body weight.

Adult↗
PubMed1999

Association of dietary intake of fat and fatty acids with risk of breast cancer.

CONTEXT: High intakes of fat and specific fatty acids, including total, animal, saturated, polyunsaturated, and trans-unsaturated fats, have been postulated to increase breast cancer risk. OBJECTIVE: To determine whether intakes of fat and fatty acids are associated with breast cancer. DESIGN AND SETTING: Cohort study (Nurses' Health Study) conducted in the United States beginning in 1976. PARTICIPANTS: A total of 88795 women free of cancer in 1980 and followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk (RR) of invasive breast cancer for an incremental increase of fat intake, ascertained by food frequency questionnaire in 1980, 1984, 1986, and 1990. RESULTS: A total of 2956 women were diagnosed as having breast cancer. Compared with women obtaining 30.1% to 35% of energy from fat, women consuming 20% or less had a multivariate RR of breast cancer of 1.15 (95% confidence interval [CI], 0.73-1.80). In multivariate models, the RR (95% CI) for a 5%-of-energy increase was 0.97 (0.94-1.00) for total fat, 0.98 (0.96-1.01) for animal fat, 0.97 (0.93-1.02) for vegetable fat, 0.94 (0.88-1.01) for saturated fat, 0.91 (0.79-1.04) for polyunsaturated fat, and 0.94 (0.88-1.00) for monounsaturated fat. For a 1% increase in energy from trans-unsaturated fat, the values were 0.92 (0.86-0.98), and for a 0.1% increase in energy from omega-3 fat from fish, the values were 1.09 (1.03-1.16). In a model including fat, protein, and energy, the RR for a 5% increase in total fat, which can be interpreted as the risk of substituting this amount of fat for an equal amount of energy from carbohydrate, was 0.96 (95% CI, 0.93-0.99). In similar models, no significant association of risk was evident with any major types of fat. CONCLUSION: We found no evidence that lower intake of total fat or specific major types of fat was associated with a decreased risk of breast cancer.

Adult↗
PubMed1999

Postmarketing surveillance and adverse drug reactions: current perspectives and future needs.

Spontaneous reporting systems like MEDWATCH can be effective in revealing unusual or rare adverse events that occur with the use of medications, and such reports may often be sufficient to assign causality. However, spontaneous reports do not reliably detect adverse drug reactions (ADRs) that occur widely separated in time from the original use of the drug or that represent an increased risk of an adverse event that occurs commonly in populations not exposed to the drug. In these situations, spontaneous reports alone do not provide sufficient evidence to conclude that the adverse event was an ADR. Identification of ADRs associated with long-term administration of drugs for chronic diseases also remains problematic. Methods to evaluate ADRs using data from clinical trials, medical records, and computerized databases of medication users and nonusers must be developed to complement spontaneous reporting systems. Without these methods, potentially important ADRs will remain undetected, and spurious associations between adverse outcomes and medications or devices will remain unchallenged.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

The role of meta-analysis in the regulatory process for foods, drugs, and devices.

Synthesis of research findings has a long-standing tradition in science. While synthesis is currently required in the US food and drug regulatory process, formal meta-analysis may substitute for a pivotal study or broaden the generalizability of drug efficacy through a preplanned meta-analysis. Preplanned meta-analysis of individual trials with deliberately introduced heterogeneity may maximize the generalizability of results from randomized trials. Combining observational data may help to support an alternative claim or to quantify adverse events. In this setting, methods to address potentially greater sources of bias are required. Overall, meta-analysis adds evidence through the synthesis study findings and permits examination of how treatment effects vary across of subgroups, such as age and sex, and across study settings.

Drug Approval↗
PubMed1999

The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer.

The A2 allele of CYP17 has been associated with polycystic ovarian syndrome, elevated levels of certain steroid hormones in premenopausal women, and increased breast cancer risk. We prospectively assessed the association between the A2 allele of CYP17 and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort. We also evaluated associations between this CYP17 genotype and plasma steroid hormone levels among postmenopausal controls not using hormone replacement to assess the biological significance of this genetic variant. Women with the A2 allele were not at an increased risk of incident breast cancer [OR (odds ratio), 0.85; 95% CI (confidence interval), 0.65-1.12] or advanced breast cancer (OR, 0.84; 95% CI, 0.54-1.32). We did observe evidence that the inverse association of late age at menarche with breast cancer may be modified by the CYP17 A2 allele. The protective effect of later age at menarche was only observed among women without the A2 allele (A1/A1 genotype: for age at menarche > or =13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2 genotypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among controls, we found women with the A2/A2 genotype to have elevated levels of estrone (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14.4%, P = 0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compared with women with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a strong independent risk factor for breast cancer.

Adult↗