From public health science to prevention policy: placing science in its social and political contexts.
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Epidemiologic Studies↗
Biomedical subjects
G A Colditz
Publications and source records attributed to G A Colditz.
Milk, dietary calcium, and bone fractures in women: a 12-year prospective study.
OBJECTIVES: This study examined whether higher intakes of milk and other calcium-rich foods during adult years can reduce the risk of osteoporotic fractures. METHODS: This was a 12-year prospective study among 77761 women, aged 34 through 59 years in 1980, who had never used calcium supplements. Dietary intake was assessed with a food-frequency questionnaire in 1980, 1984, and 1986. Fractures of the proximal femur (n = 133) and distal radius (n = 1046) from low or moderate trauma were self-reported on biennial questionnaires. RESULTS: We found no evidence that higher intakes of milk or calcium from food sources reduce fracture incidence. Women who drank two or more glasses of milk per day had relative risks of 1.45 for hip fracture (95% confidence interval [CI] = 0.87, 2.43) and 1.05 for forearm fracture (95% CI = 0.88, 1.25) when compared with women consuming one glass or less per week. Likewise, higher intakes of total dietary calcium or calcium from dairy foods were not associated with decreased risk of hip or forearm fracture. CONCLUSIONS: These data do not support the hypothesis that higher consumption of milk or other food sources of calcium by adult women protects against hip or forearm fractures.
Adolescent↗
A prospective study of oral contraceptives and NIDDM among U.S. women.
OBJECTIVE: To examine prospectively the association between modern oral contraceptives with low doses of estrogen and progestin and subsequent incidence of NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 98,590 U.S. female nurses aged 25 to 42 and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline in 1989 were followed for 4 years. Endpoint was incidence of confirmed NIDDM. Oral contraceptive use was reported on mailed questionnaires. RESULTS: During 352,067 person-years follow-up, we confirmed 185 incident cases of NIDDM. After adjusting for age, BMI, cigarette smoking, family history of diabetes, parity, physical activity, alcohol intake, ethnicity, history of diagnosis of infertility, elevated cholesterol, and hypertension, women currently using oral contraceptives had a relative risk (RR) of 1.6 (95% CI, 0.9-3.1). For past users, the multivariate RR was 1.2 (95% CI, 0.8-1.8). This association was attenuated after restricting the analysis to symptomatic cases of NIDDM. For current users, RR = 1.3 (95% CI, 0.6-2.8), and for past users, RR = 0.9 (95% CI, 0.6-1.4), suggesting that increased surveillance may explain at least part of any excess risk. CONCLUSIONS: In this large prospective study, we found no appreciable increase in the 4-year risk of NIDDM among current users of oral contraceptives. There was no apparent increase in risk among past users. The small number of cases reflect the low absolute risk of NIDDM in this population of young women.
Adult↗
Dietary fiber, glycemic load, and risk of NIDDM in men.
OBJECTIVE: Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS: We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40-75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS: The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02-1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51-0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04-4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.
Adult↗
A prospective study of reproductive factors, oral contraceptive use, and risk of colorectal cancer.
To explore the roles of reproductive factors and oral contraceptive use in the etiology of colorectal cancer, we examined incident cases of colorectal cancer (n = 501) that occurred during 1,012,280 person-years of follow-up between 1980 and 1992 in the Nurses' Health Study. The women completed mailed, self-administered questionnaires every 2 years to update information on the risk factors and major medical events. In multivariate analysis, the relative risk (RR) of colorectal cancer among women who experienced menarche at age 14 or older was 0.83 (95% confidence interval (CI) = 0.64-1.08) compared with women who had menarche at age 13; women whose menarche occurred under age 12 were at higher risk (RR = 1.22; 95% CI = 0.96-1.55, P for trend = 0.01). Compared with women whose first pregnancy was before age 24, the risk for colorectal cancer was significantly increased among women whose first pregnancy was at age 30 or older (RR = 1.57; 95% CI = 1.15-2.14; P for trend = 0.02). No important associations were seen for parity or age at menopause. Women who used oral contraceptives for 96 months or longer had a 40% lower risk of developing colorectal cancer (RR = 0.60; 95% CI = 0.40-0.89; P for trend = 0.02) compared with women who never used oral contraceptives. These prospective data suggest that a later age of menarche and use of oral contraceptives may reduce risk of colorectal cancer, whereas women with a later age at first pregnancy may have a higher risk.
Adult↗
Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types.
Epidemiological studies using the histological classification of Page for benign breast disease consistently demonstrate a positive association between atypical hyperplasia and the subsequent development of breast cancer. However, atypical hyperplasia is of either lobular or ductal types, and breast cancer risk in relation to type of atypical hyperplasia has not been studied extensively. Thus, we investigated prospectively the risk of breast cancer associated with histological subtypes of benign proliferative breast disease, including the types of atypical hyperplasia, among participants in the Nurses' Health Study who had biopsy-confirmed benign breast disease. Women who subsequently developed breast cancer were matched by year of birth and year of biopsy to participants who were free from breast cancer. Benign biopsy slides were classified according to the criteria of Page. Odds ratios (ORs) of breast cancer and 95% confidence intervals (CIs), adjusted for the matching variables and other breast cancer risk factors, were computed using unconditional logistic regression with benign nonproliferative breast disease as the referent group. Atypical ductal hyperplasia (OR = 2.4; 95% CI, 1.3-4.5) or atypical lobular hyperplasia (OR = 5.3; 95% CI, 2.7-10.4) in a prior biopsy were associated with increased breast cancer risk. Atypical lobular hyperplasia was more strongly associated with the risk of premenopausal breast cancer (OR = 9.6; 95% CI, 3.3-27.8) than with the risk of postmenopausal breast cancer (OR = 3.7; 95% CI, 1.3-10.2). The association of atypical ductal hyperplasia and breast cancer risk varied little by menopausal status. The magnitude of breast cancer risk seems to vary according to the type of atypical hyperplasia present at biopsy.
Adult↗
Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.
A common deletion polymorphism in the gene coding for the glutathione S-transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify carcinogenic epoxide intermediates and has been associated with increased breast cancer risk in some small studies. We studied the GSTM1 gene deletion polymorphism (conferring the null genotype) in 243 women who had prevalent breast cancer and 245 women without breast cancer, who were among the 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent case series, the null genotype was slightly more common among cases (58%) than among controls (51%; age-adjusted odds ratio = 1.30; 95% confidence interval, 0.91-1.86). Among cases, the prevalence of the GSTM1 deletion increased with duration of survival [68% for > or = 8 years since diagnosis; 57% for 4-8 years; 51% for < 4 years; P (trend) = 0.04]. In an incident case series of 240 women who were diagnosed with breast cancer following blood collection and prior to June of 1992 and compared with age-matched controls, the GSTM1 deletion was not associated with an elevation in risk (relative risk, 1.08; 95% confidence interval, 0.74-1.57). No significant interaction with cigarette smoking was evident. Thus, there was no significant increase in risk of incident breast cancer associated with the GSTM1 null genotype; however, the gene deletion polymorphism appeared to confer improved survival. These data suggest that odds ratios based upon prevalent cases in molecular epidemiologic studies may be biased due to differential survival. Further studies are required to determine whether this polymorphism is associated with improved breast cancer prognosis.
Adult↗
Height, body weight, and risk of prostate cancer.
Using data from the Health Professionals Follow-Up Study, we prospectively examined the relationships between height, body mass index, waist and hip circumferences, and risk of total and advanced (extraprostatic and metastatic) prostate cancer. In addition, we assessed adiposity during childhood, adolescence, and early, middle, and late adulthood using pictograms in relation to prostate cancer risk. Between 1986 and 1994, 1,369 cases of prostate cancer (excluding stage A1) were confirmed in 47,781 men. Adult body mass index and waist and hip circumferences were not appreciably related to risk of total prostate cancer or advanced prostate cancer. In contrast, preadult (age 10) obesity assessed in 33,336 men in 1988 was prospectively related to lower risk of advanced [relative risk (RR) = 0.72 with 95% confidence interval (CI) = 0.47-1.10, between high and low quintiles; P(trend) = 0.06] and metastatic prostate cancer (RR = 0.38 with 95% CI = 0.19-0.77; P(trend) = 0.004). For the advanced lesions, an association was observed with height (RR = 1.68 with 95% CI = 1.16-2.43 for men 74 inches or taller, relative to men 68 inches or shorter; P(trend) = 0.01). In an analysis limited to particularly aggressive forms of prostate cancer, i.e., cases found to be metastatic at time of diagnosis between 1988 and 1994 after a negative digital rectal examination in 1988, we found that obesity at ages 5 and 10 had a strong inverse association (RR = 0.16 with 95% CI = 0.05-0.54, between high and low quintiles at age 10) and that tallness had a strong direct association with risk of metastatic disease (RR = 2.29 with 95% CI = 1.04-5.05, for height > or = 74 inches versus < or = 68 inches). Our findings suggest that the preadult hormonal milieu, as reflected in attained height and childhood obesity, may have a strong influence on prostate carcinogenesis.
Adolescent↗
Dietary fiber and distal colorectal adenoma in men.
We evaluated the relation of specific sources and components of fiber with diagnosis of distal colon (n = 531) or rectal (n = 159) adenomatous polyps or hyperplastic (n = 327) polyps in the Health Professionals Follow-up Study. We studied 16,448 men free of cancer or polyps in 1986, who underwent endoscopy in 1986-1994, and who provided diet and medical history. Relative risks (RRs) and 95% confidence intervals (CIs) adjusted using multiple logistic regression were calculated. We observed a modest reduced risk of distal colon adenoma with increasing intake of fiber from fruit (P-trend = 0.03) but not cereals or vegetables. The RR comparing the highest (median, 8.4 g/day) to lowest (1.3 g/day) quintile of fruit fiber intake was 0.81 (95% CI, 0.59-1.11). Soluble fiber, but not insoluble fiber, appeared to be inversely associated with distal colon adenoma (P-trend = 0.007). Comparing extreme quintiles (9.4 versus 3.4 g/day soluble fiber), the RR was 0.69 (95% CI, 0.46-1.03). Polyps detected in 1986 or later among men also with a negative endoscopy before 1986 may be considered to be "incident," with diet report corresponding more closely to time of polyp development. For "incident" cases (n = 130), the relation between soluble fiber and distal colon adenoma was strengthened (extreme quintiles RR, 0.27; 95% CI, 0.11-0.66; P-trend = 0.003), whereas for "prevalent" cases (n = 401), we found no association. No consistent relation between fiber and rectal adenomas or hyperplastic polyps was observed. These results suggest that soluble fiber may be particularly important in reducing risk of adenomatous polyps of the distal colon and support national dietary guidelines of increasing fruit consumption.
Adenoma↗
Estrogen replacement therapy for breast cancer patients.
Female reproductive hormones cause breast cancer. Long-term use of postmenopausal hormones increases the risk of breast cancer. The apparent survival advantage seen in women diagnosed with breast cancer while taking postmenopausal hormones may be due to the hormone-responsive nature of their tumors, diagnosis at an earlier stage, or other biases. Thus, the data indicating a survival advantage do not specify what the policies were on the use of hormones after diagnosis. Substantial evidence from studies of obesity confirms the association of higher estrogen levels with poorer prognosis. Tamoxifen (Nolvadex), acting as an antiestrogen in breast tissue, increases the likelihood of survival, as does oophorectomy in premenopausal women. Given these data, women diagnosed with breast cancer should use hormones sparingly. Alternatives to hormone therapy should be used for long-term prevention of heart disease and osteoporosis.
Breast Neoplasms↗
Selenium and cancer prevention. Promising results indicate further trials required.
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Anticarcinogenic Agents↗
Evaluation of tuberculosis control policies using computer simulation.
OBJECTIVE: To develop more effective methods to assess tuberculosis (TB) control strategies so we can meet national goals for the elimination of TB in the United States. DESIGN: Using a semi-Markov model that divided the US population into 3 age groups and 18 clinical states based on disease status and risk for TB and human immunodeficiency virus (HIV) infection, we measured the effects of 5 changes in TB policy, introduced singly and in combination: (1) increased coverage and (2) improved efficacy of preventive therapy, (3) increased coverage and (4) improved efficacy of treatment, and (5) introduction of BCG vaccination. RESULTS: A BCG vaccination program that reached 10% of eligible children and 1% of eligible adults each year would produce a 17% reduction in cases and an 11% decline in deaths over 10 years. Preventive therapy programs among the general population would have little effect on the number of TB cases, but a program targeting HIV-infected patients would reduce HIV-associated TB cases and deaths 14% to 20%. A 10% improvement in the coverage and efficacy of both preventive therapy and treatment, coupled with the BCG vaccination program, would lead to a 47% decline in TB cases and a 50% decline in TB deaths relative to baseline over 10 years. CONCLUSIONS: Improvements in treatment coverage or effectiveness alone are unlikely to reach established national goals for the elimination of TB. These goals can be achieved through a combination of improvements in current programs with targeted preventive therapy and BCG vaccination programs.
Adolescent↗
Birthweight as a risk factor for breast cancer.
BACKGROUND: The mammary gland is largely undifferentiated before birth and may be particularly susceptible to intrauterine influences that could increase the risk of cancer through acceleration of cell proliferation or other pregnancy-related processes. Studies of migrant populations, animal data, and limited epidemiological evidence suggest that breast cancer may originate in utero. In a nested case-control study we assessed whether birthweight and other perinatal factors are associated with risk of breast cancer. METHODS: This case-control study was nested within the cohorts of the two Nurses' Health Studies. We used self-administered questionnaires to obtain information from the mothers of 582 nurses with invasive breast cancer and the mothers of 1569 nurses who did not have breast cancer (controls). Information on risk factors for breast cancer during adulthood were obtained from the nurses; multiple logistic regression analysis adjusted for these risk factors. FINDINGS: Birthweight was a significant predictor of breast-cancer risk. With women who weighed 4000 g or more at birth as the reference category, the adjusted odds ratios for breast cancer were 0.86 (95% CI 0.59-1.25) for birthweights of 3500-3999 g, 0.68 (0.48-0.97) for birthweights of 3000-3499 g, 0.66 (0.45-0.98) for birthweights of 2500-2999 g, and 0.55 (0.33-0.93) for birthweights below 2500 g (p for trend 0.004). Prematurity was not significantly associated with risk of breast cancer. INTERPRETATION: Birthweight is significantly associated with breast-cancer risk, which suggests that intrauterine factors or processes affect the risk of breast cancer in the offspring. High concentrations of pregnancy oestrogens may have an important role in breast carcinogenesis, but other pregnancy hormones or intrauterine factors may also be involved.
Adult↗
Invited commentary: confounding, measurement error, and publication bias in studies of passive smoking.
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Confounding Factors, Epidemiologic↗
A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer.
We examined the relationship of a common polymorphism (667C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene with the risk of colorectal cancer in a case-control study conducted in the Health Professionals Follow-up Study. MTHFR genotypes were ascertained from blood samples among 144 men previously diagnosed with colorectal cancer and 627 controls. The adjusted odds ratio (OR) for the MTHFR variant homozygous (val/val) genotype was 0.57 [95% confidence interval (CI), 0.30-1.06]. High dietary intake of methionine (OR, 0.27; 95% CI, 0.06-1.20) and low consumption of alcohol (OR, 0.11; 95% CI, 0.01-0.85) were associated with reduced incidence of colorectal cancer. Alcohol intake was a stronger risk factor among men with the val/val genotype (P, trend = 0.01), and consumption of five or more alcoholic drinks per week abolished the reduced risk of colorectal cancer among val/val individuals (P, interaction = 0.02). The inverse association of methionine with colorectal cancer risk was slightly stronger among individuals with the MTHFR val/val genotype. These data suggest that dietary methyl supply is particularly critical among MTHFR val/val individuals. When dietary methyl supply is high, MTHFR val/val individuals may be at reduced risk of colorectal cancer probably because higher levels of 5,10-methylenetetrahydrofolate may prevent imbalances of nucleotide pools during DNA synthesis. In contrast, when 5-methyltetrahydrofolate is depleted by alcohol consumption, val/val individuals may be less able to compensate, leading to potentially oncogenic alterations in DNA methylation.
Adult↗
A prospective study of cigarette smoking and the risk of pancreatic cancer.
OBJECTIVES: To prospectively examine the excess incidence of pancreatic cancer among cigarette smokers and to examine the influence of smoking cessation on the risk of pancreatic cancer. METHODS: We obtained data on cigarette smoking and other risk factors for pancreatic cancer from 118,339 women aged 30 to 55 years and 49,428 men aged 40 to 75 years who were without diagnosed cancer. During the 2,116,229 persons-years of follow-up, pancreatic cancer was diagnosed in 186 participants. RESULTS: The multivariate relative risk of pancreatic cancer for current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant, positive trend in risk with increasing pack-years of smoking was observed (P for trend = .004), although this association was confined to cigarette consumption within the past 15 years. Compared with participants who continued to smoke, former smokers had a 48% reduction in pancreatic cancer risk within 2 years of quitting. Ultimately, the relative risk of pancreatic cancer among former smokers approached that for never smokers after less than 10 years of smoking cessation. Overall, the proportion of pancreatic cancers attributable to cigarette smoking was 25%. CONCLUSIONS: Cigarette smoking is associated with an increased risk of pancreatic cancer. The rapid reduction in risk associated with quitting suggests that smoking cessation could eliminate 25% of the 27,000 deaths from pancreatic cancer occurring annually in the United States.
Adult↗
Prospective study of exogenous hormones and risk of pulmonary embolism in women.
BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. METHODS: In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. FINDINGS: From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.
Adult↗
Calcium, vitamin D, and the occurrence of colorectal cancer among women.
BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.
Adult↗