Pamela J. Mink

DIETARY ANTIOXIDANT VITAMINS AND DEATH FROM CORONARY HEART DISEASE IN POSTMENOPAUSAL WOMEN

Background. The role of dietary antioxidant vitamins in preventing coronary heart disease has aroused considerable interest because of the knowledge that ox- idative modification of low-density lipoprotein may pro- mote atherosclerosis. Methods. We studied 34,486 postmenopausal wom- en with no cardiovascular disease who in early 1986 com- pleted a questionnaire that assessed, among other fac- tors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease. Results. In analyses adjusted for age and dietary en- ergy intake, vitamin E consumption appeared to be in- versely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21,809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42, and 0.42; P for trend � 0.008). After adjustment for possible con- founding variables, this inverse association remained (rel- ative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32, and 0.38; P for trend � 0.004). There was little evi- dence that the intake of vitamin E from supplements was associated with a decreased risk of death from coronary heart disease, but the effects of high-dose supplementa- tion and the duration of supplement use could not be de- finitively addressed. Intake of vitamins A and C did not appear to be associated with the risk of death from cor- onary heart disease. Conclusions. These results suggest that in postmeno- pausal women the intake of vitamin E from food is inverse- ly associated with the risk of death from coronary heart disease and that such women can lower their risk without using vitamin supplements. By contrast, the intake of vita- mins A and C was not associated with lower risks of dying from coronary disease. (N Engl J Med 1996;334:1156-62.)

Racial disparities in incidence and outcome in multiple myeloma: a population-based study

Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some prior studies suggest inferior survival in blacks; others suggest similar survival. Using the original 9 Surveillance, Epidemiology, and End Results registries, we conducted a large-scale population-based study including 5798 black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006. Age-adjusted incidence rates, disease-specific survival, and relative survival rates were calculated by race, age, and time period of diagnosis. Mean age at diagnosis was 65.8 and 69.8 years for blacks and whites, respectively (P < .001). Incidence among blacks was m twice that among whites; this disparity was greater among patients < 50 years (P = .002). Over the entire study period, disease-specific and relative survival rates were higher in blacks than whites (P < .001). For whites, 5-year relative survival rates increased significantly 1973-1993 to 1994-1998 (26.3% to 30.8%; P < .001) and 1994-1998 to 1999-2005 (30.8% to 35.0%; P = .004). Survival improvements among blacks were smaller and nonsignificant (1973-1993 to 1999-2005: 31.0% to 34.1%; P = .07). We found (1) a younger age of onset among blacks; (2) better survival in blacks 1973-2005; and (3) significant survival improvement among whites over time, with smaller, nonsignificant change seen among blacks, possibly due to unequal access to and/or disparate responsiveness to novel therapies.

Dietary flavonoid intake and risk of cancer in postmenopausal women: The Iowa Women's Health Study

Flavonoids, which are found in certain plant foods, are thought to lower cancer risk through their antioxidant, antiestrogenic and antiproliferative properties. We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung, colorectal, breast, pancreatic and upper aerodigestive cancer among women in a large prospective cohort study. Study participants were 34,708 postmenopausal women in the Iowa Womens Health Study who completed a food frequency questionnaire and were followed for cancer occurrence from 1986 through 2004. Flavonoid intake was estimated from 3 databases developed by the USDA Nutrient Data Laboratory (NDL). Hazard ratios (HR) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories. Interactions between smoking history and flavonoid intake were also examined. After multivariable adjustment, lung cancer incidence was inversely associated with intakes of flavanones (HR = 0.68; 95% CI: 0.53–0.86, all results highest vs. lowest quintile) and proanthocyanidins (HR = 0.75; 95% CI: 0.57–0.97). Among current and past smokers, those with intakes in the highest quintile for flavanones (HR = 0.66; 95% CI: 0.50–0.86), and proanthocyanidins (HR = 0.66; 95% CI; 0.49–0.89) had significantly lower lung cancer incidence than those in the lowest quintile. Similar associations were not seen in never smokers. Isoflavone intake was inversely associated with overall cancer incidence (HR = 0.93, 95% CI: 0.86–1.00). This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk, especially among current and past smokers.

Physical activity, waist-to-hip ratio, and other risk factors for ovarian cancer : a follow-up study of older women

We investigated the association of epithelial ovarian cancer with physical activity, waist-to-hip ratio, reproductive factors, and family history of cancer in a prospective cohort study of 31,396 postmenopausal women. Ninety-seven women developed incident epithelial ovarian cancer over 7 years. The number of livebirths was associated with lower risk (multivariate-adjusted relative risks for 1–2, 3–4, and ≤4 livebirths compared with nulliparity were 0.64, 0.47, and 0.43, respectively). A family history of ovarian cancer in a first-degree relative was associated with a 2.5 times greater risk (95% confidence interval = 0.90–6.7). Multivariate-adjusted relative risks for the upper three quartiles of waist-to-hip ratio compared with the lowest quartile were 2.0, 1.6, and 2.3, respectively. Women with “moderate” and “high” levels of physical activity compared with those with “low” physical activity had relative risks of 1.4 and 2.1, respectively. Positive associations of physical activity and waist-to-hip ratio with ovarian cancer seem inconsistent with existing theories of ovarian cancer pathogenesis.

HDL-cholesterol and incidence of breast cancer in the ARIC cohort study

PURPOSE An association of low plasma HDL-cholesterol with risk of breast cancer has been suggested by multiple studies; the evidence, however, is not conclusive. We examined the possible association of low HDL-cholesterol with incidence of breast cancer using data from the Atherosclerosis Risk in Communities Study (ARIC) cohort, a prospective study of a randomly selected sample of women and men from four U.S. communities. METHODS Among 7,575 female members of the ARIC cohort, 359 cases of incident breast cancer were ascertained during the follow-up from 1987 through 2000. RESULTS In analysis adjusted for age, race, body mass index, smoking, and reproductive variables, we observed no association of low baseline HDL-cholesterol (<50mg/dL) with incident breast cancer in the total sample (hazard ratio [HR]=1.08 [95% confidence interval (CI), 0.84-1.40]) and a modest association (HR=1.67 [95% CI, 1.06-2.63]) among women who were premenopausal at baseline. No association was observed among women who were postmenopausal at baseline. Removal from analysis of the first 5 years of follow-up did not appreciably change the observed associations. CONCLUSION Results of our study suggest that low HDL-cholesterol among premenopausal women may be a marker of increased breast cancer risk.

A REVIEW AND META-ANALYSIS OF PROSPECTIVE STUDIES OF RED AND PROCESSED MEAT INTAKE AND PROSTATE CANCER

Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption (SRRE = 1.00, 95% CI: 0.96-1.05) or each 100 g increment of red meat (SRRE = 1.00, 95% CI: 0.95-1.05) and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer (SRRE = 1.01, 95% CI: 0.94-1.09). A weakly elevated summary association between processed meat and total prostate cancer was found (SRRE = 1.05, 95% CI: 0.99-1.12), although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer.

Evaluation of epidemiologic and animal data associating pesticides with Parkinson's disease

Exposure to pesticides may be a risk factor for developing Parkinson’s disease (PD). To evaluate the evidence regarding this association in the scientific literature, we examined both analytic epidemiologic studies of PD cases in which exposure to pesticides was queried directly and whole-animal studies for PD-like effects after systemic pesticide exposure. Epidemiologic studies were considered according to study quality parameters, and results were found to be mixed and without consistent exposure-response or pesticide-specific patterns. These epidemiologic studies were limited by a lack of detailed and validated pesticide exposure assessment. In animal studies, no pesticide has yet demonstrated the selective set of clinical and pathologic signs that characterize human PD, particularly at levels relevant to human populations. We conclude that the animal and epidemiologic data reviewed do not provide sufficient evidence to support a causal association between pesticide exposure and PD.

Physical activity and incidence of postmenopausal breast cancer

Whether physical activity reduces the risk of postmenopausal breast cancer is uncertain; few studies have addressed this issue. We examined the association of leisure physical activity with breast cancer incidence among 37,105 postmenopausal participants in the Iowa Womens Health Study. Women reporting the highest level of physical activity at baseline compared with women with the lowest level of activity had an age-adjusted relative risk of breast cancer of 0.92 (95% confidence interval = 0.80-1.05). Women reporting any regular leisure-time physical activity had a relative risk of 0.97 (95% confidence interval = 0.87-1.08) compared with those reporting no such regular physical activity. Adjustment for potential confounders did not appreciably alter the findings. There is little evidence from this study that physical activity later in life is associated to any appreciable extent with breast cancer incidence.

US mesothelioma patterns 1973-2002: Indicators of change and insights into background rates

Mesothelioma rates are declining toward background levels, although estimates of the background rate have varied. We expanded upon earlier analyses and provided a data-based estimate of the background rate. We analyzed US male and female patterns for five age groups using the National Cancer Institutes Surveillance Epidemiology and End Results registry data from 1973 to 2002. Age-specific and age-adjusted incidence rates per 1 000 000 persons per year, standardized to the 2000 US population, were calculated for total, pleural, and peritoneal mesothelioma. We also calculated rates for persons who attained working age after the US Occupational Safety and Health Administration asbestos exposure limits took effect. Mesothelioma rates observed among young males and females varied little over time. We observed a decline and convergence of recent male and female rates in older age groups, except those who are between the age of 60 and above, for whom the 2002 male rate was approximately five times greater than that of females. As expected, rates were higher in major shipyard areas on the West coast. Rates for persons with little or no opportunity for occupational asbestos exposure were 1.15 (95% confidence interval: 0.90–1.45) for men and 0.94 (95% confidence interval: 0.87–1.24) for women. Mesothelioma is rare in younger age groups, and rates have been relatively stable and similar for both sexes. Rates continue to decline in older age groups, but remain high for males at 60 years or older. Rates among females at older ages suggest an impact of occupational exposure. The background rate for persons below age 50 is approximately one per million, independent of sex. Future data are needed to estimate this rate for older age groups.

Evaluation of uncontrolled confounding in studies of environmental exposures and neurobehavioral testing in children.

Background: Neurobehavioral tests are commonly used in studies of children exposed to low-level environmental concentrations of compounds known to be neurotoxic at higher levels. However, uncontrolled or incomplete control for confounding makes interpretation of results problematic because effects of confounders are often stronger than the effects of primary interest. We examined a priori the potential impact of confounding in a hypothetical study evaluating the association of a potentially neurotoxic environmental exposure with neurobehavioral function in children. Methods: We used 2 outcome measures: the Bayley Scales of Infant Development Mental Development Index and the Stanford-Binet Intelligence Scale Composite Score. We selected 3 potential confounders: maternal intelligence, home environment, and socioeconomic status as measured by years of parental education. We conducted 3 sets of analyses measuring the effect of each of the 3 confounding factors alone, 2 confounders acting simultaneously, and all 3 confounders acting simultaneously. Results: Relatively small differences (0.5 standard deviations) in confounding variables between “exposed” and “unexposed” groups, if unmeasured and unaccounted for in the analysis, could produce spurious differences in cognitive test scores. The magnitude of this difference (3–10 points) has been suggested to have a meaningful impact in populations. The method of measuring confounders (eg, maternal intelligence) could also substantially affect the results. Conclusions: It is important to carefully consider the impact of potential confounders during the planning stages of an observational study. Study-to-study differences in neurobehavioral outcomes with similar environmental exposures could be partially explained by differences in the adjustment for confounding variables.