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M Kulldorff

Publications and source records attributed to M Kulldorff.

At least 19 recordsLinked to original sources
PubMed2000

Geographic variation in prostate cancer mortality rates among white males in the united states.

PURPOSE: The most recent atlas of cancer mortality in the United States revealed elevated prostate cancer mortality rates among white males in the northwest, Rocky Mountain, northcentral, and southeast areas, as well as New England, especially during the 1970-94 period. We wanted to test whether this observed geographic variation was simply due to chance or not.METHODS: We used a spatial scan statistic using mortality data for 506 state economic areas.RESULTS: There were four significant clusters with elevated risks of prostate cancer mortality (P < 0.001). The most prominent cluster was in the northwestern quadrant of the country, followed by clusters in New England, the midwest, and southeast regions. Within the northwestern cluster, we also detected seven significant sub-clusters (P < 0.05).CONCLUSIONS: We concluded that the observed geographic variation of prostate cancer mortality is indeed real, and deserves further study into the underlying determinants.

Journal Article↗
PubMed2000

Evaluation of alternative approaches to assign nutrient values to food groups in food frequency questionnaires.

Although every food frequency questionnaire (FFQ) requires a nutrient database to produce nutrient intake estimates, it is often unclear how a particular database has been generated. Moreover, alternative methods for constructing a database have not been rigorously evaluated. Using 24-hour recalls from the 1994-1996 Continuing Survey of Food Intake by Individuals, the authors categorized 5,261 individual foods reported by 10,019 adults into 170 food groups consistent with line items on an FFQ. These food groups were used to generate 10 potential nutrient databases for a FFQ that varied by whether the authors 1) used means or medians, 2) did or did not consider age, 3) incorporated collapsing strategies for small age-gender-portion size cells, 4) excluded outliers in a regression, and 5) used weighted median nutrient density x age-gender-portion size-specific median gram weights (Block method). Mean error, mean squared error, and mean absolute error were calculated and compared across methods, with error being the difference in total observed (from recalls for each individual) and total estimated intake (from each of the 10 methods) for seven nutrients. Mean methods for assigning nutrients to food groups were superior to median approaches for all measurements. Among the mean methods, no single variation was consistently better.

Adult↗
PubMed2000

Dietary heterocyclic amines and the risk of lung cancer among Missouri women.

Heterocyclic amines (HCAs) such as 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx,), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are found in meats cooked at high temperatures. In rodents, MeIQx induces lung tumors. The purpose of this study was to investigate lung cancer risk posed by different HCAs in the diet. A population-based case-control study of 593 cases and 623 frequency-matched controls including both nonsmoking and smoking women was conducted in Missouri. An administered food frequency questionnaire with detailed questions on meat consumption, degrees of internal doneness, surface browning/charring, and cooking technique was linked to a database that provided exposure estimates of three HCAs. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. When comparing the 90th and 10th percentiles, significant excess risks were observed for MeIQx (OR, 1.5; CI, 1.1-2.0), but not for DiMeIQx (OR, 1.2; CI, 0.9-1.6) or PhIP (OR, 0.9; CI, 0.8-1.1). MeIQx consumption was associated with increased risk of lung cancer for nonsmokers (OR, 3.6; CI, 1.3-10.3) and light/moderate smokers (OR, 2.1; CI, 1.3-3.3), but not for heavy smokers (OR, 1.0; CI, 0.7-1.5). There was elevated risk with MeIQx intake for subjects with squamous cell carcinomas (OR, 1.9; CI, 1.2-3.1) and "other histological cell types" (OR, 1.6; CI, 1.1-2.5), but not for subjects with small cell carcinomas and adenocarcinomas. Neither DiMeIQx nor PhIP showed an association with smoking categories or lung cancer histology. In conclusion, MeIQx may be associated with lung cancer risk, but DiMeIQx and PhIP are probably not associated with lung cancer risk.

Adenocarcinoma↗
PubMed2000

Dietary fat, fat subtypes, and breast cancer in postmenopausal women: a prospective cohort study.

BACKGROUND: The intake of total dietary fat and of certain fat subtypes has been shown to be strongly associated with breast cancer in international comparisons and in animal experiments. However, observational epidemiologic studies have generally reported either weak positive or no associations. To extend the prospective epidemiologic evidence on this question, we examined the association between adult dietary intake of fat, fat subtypes, and breast cancer in a large, prospective cohort of postmenopausal women. METHODS: Participants were selected from a national breast cancer mammography screening program conducted from 1973 through 1981 at 29 centers throughout the United States. From 1987 through 1989, 40022 postmenopausal women satisfactorily completed a mailed, self-administered questionnaire that included a 60-item National Cancer Institute/Block food-frequency questionnaire. Women were then followed for an average of 5.3 years; 996 women developed breast cancer. Risk was assessed by use of Cox proportional hazard regression, with age as the underlying time metric. All statistical tests were two-sided. RESULTS: Compared with women in the lowest quintile (Q1) of percentage of energy from total fat, the adjusted risk ratio (RR) and 95% confidence interval (CI) for women in the highest quintile (Q5) was 1.07 (95% CI = 0.86-1.32). In analyses stratified by history of benign breast disease (BBD), a positive association was observed among only women with no history of BBD (RR (Q5 versus Q1) = 2.20; 95% CI = 1.41-3.42; test for trend, P =.0003). The increased risk in these women appeared to be attributable to unsaturated fat intake and oleic acid in particular. CONCLUSIONS: In this study, there was no overall association between fat intake during adulthood and breast cancer risk; however, among women with no history of BBD, there appeared to be a positive association between total and unsaturated fat intake and breast cancer risk.

Breast Neoplasms↗
PubMed2000

Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays.

Cell proliferation in the human colorectum can be measured using bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays. Using data from the National Cancer Institute's Polyp Prevention Trial, these two assays are compared using correlation coefficients and variance components analysis. Adjusting for fixed as well as for the random effects of between-biopsy and scoring variation, the estimated correlation is 0.46 for the log labeling index and 0.45 for log proliferative height. This is an estimate of the highest correlation that can be achieved by taking multiple biopsies scored by multiple scorers. For single biopsies, the estimated correlation is 0.16 and 0.10, respectively. There are significant differences between the variance components for the two assays. For example, for log labeling index, PCNA has a lower variation between biopsies than BrdU, but higher variation between scorings. When used in a clinical or epidemiological setting, it is important to take multiple biopsies at multiple time points.

Adenoma↗
PubMed2000

Comparing odds ratios for nested subsets of dietary components.

BACKGROUND: In nutritional epidemiology, it is often of interest to disentangle the risk of disease associated with related foods or nutrients, where the food items are in a nested arrangement within a larger group. To compare odds ratios (OR) derived from a standard quantile-based analysis can be misleading since the amounts consumed may differ substantially for different dietary components. METHODS: The authors applied different logistic regression models on a case-control study concerning the risk of colorectal adenomas due to meat and its different subsets such as white meat, red meat and well-done red meat. RESULTS: By calculating OR for a fixed amount of intake, the authors suggest a method for partitioning the risk of one dietary item into that associated with increasingly detailed sub-components. A graph is presented for illustrating such partitions in terms of both addition and substitution effects. CONCLUSIONS: Odds ratios based on upper versus lower quantiles or percentiles are useful as they compare the risk between the upper and lower ends of the consumption range. A complimentary set of OR are those based on fixed amounts of consumption. These allow for direct comparisons between nested subgroups of dietary components, in order to disentangle the risk linked to specific groups of foods or nutrients.

Adenoma↗
PubMed2000

The effect of low dose micronized 17ss-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study.

The purpose of this study was to examine the effects of three doses (0.25, 0.5, and 1.0 mg/day) of micronized 17ss-estradiol on bone turnover, sex hormone levels, and side effects compared with placebo in healthy older women. The study design was randomized, double blind, and placebo controlled. The setting was a university clinical research center. Healthy, community-living women over 65 yr of age participated in the study. The main outcome measures were serum and urinary biochemical markers of bone resorption and formation at baseline, 6 and 12 weeks on treatment, and 6 and 12 weeks off treatment. Markers of bone resorption were N-telopeptides of type I collagen, C-telopeptides of type I collagen, and total deoxypyridinoline cross-links; formation markers were bone alkaline phosphatase, osteocalcin, and N-terminal procollagen peptides. We also measured serum estradiol, estrone, and sex hormone-binding globulin levels at baseline, 12 weeks on treatment, and 12 weeks posttreatment. All markers of bone resorption significantly decreased at 12 weeks on treatment compared with placebo and returned toward baseline at 12 weeks posttreatment. Two markers of bone formation, bone alkaline phosphatase and N-terminal procollagen peptides, significantly decreased 12 weeks posttreatment, but the decrease in osteocalcin varied with time and estrogen dose. Based on equivalence testing, the response of markers of bone turnover to therapy with 0.25 mg/day was similar to that seen with 1.0 mg/day. Serum estradiol increased compared with baseline in all treatment groups and compared with placebo in the two higher dose groups. Breast tenderness, bleeding, and endometrial changes were significantly less frequent in the 0.25 mg/day and placebo groups compared with the higher dose groups. We conclude that low dose of estrogen (0.25 mg/day 17ss-estradiol) reduced bone turnover to a similar degree as that seen with usual replacement therapy (1.0 mg/day 17ss-estradiol), but had a side effect profile similar to that of placebo. In our study additional increases in estradiol levels, as seen with 0.5 and 1.0 mg/day 17ss-estradiol treatment, resulted in more side effects without evidence of additional benefit to bone. These data suggest that 0.25 mg/day 17ss-estradiol may be an effective and tolerable agent for the treatment of osteoporosis in older women.

Aged↗
PubMed1999

Maternal supplemental and dietary zinc intake and the occurrence of neural tube defects in California.

The authors investigated the association between maternal preconceptional supplemental and dietary zinc intake and risk of neural tube defects (NTDs) in a population-based case-control study conducted between 1989 and 1991 in California. Cases were 430 NTD-affected fetuses/infants, and controls were 429 randomly selected non-malformed infants. Mothers reported their preconceptional use of vitamin, mineral, and food supplements, and completed a 98-item food frequency questionnaire. Increased total preconceptional zinc intake was associated with a reduced risk for NTDs (quintile 5 vs. quintile 1, odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.43, 0.99). Phytate intake, a constituent of the diet known to impede zinc absorption, appeared to modify the zinc - NTD association. In addition, increased servings of animal products, the most bioavailable food source of zinc, was associated with a reduced risk for NTDs (quintile 5 vs. quintile 1, OR = 0.49, 95% CI 0.32, 0.76). Risk estimates for zinc intake were changed little after controlling for multiple sociodemographic factors and total folate intake, but were attenuated after controlling for nutrients highly correlated with dietary sources of zinc, such as protein. In sum, the analyses indicate that risk of NTDs in infants and fetuses decreased with increasing maternal preconceptional zinc intake. However, it remains unclear whether increased zinc intake, or another nutrient or combination of nutrients highly correlated with zinc intake in the diet, is causally associated with reduced NTD risk.

Body Mass Index↗
PubMed1999

Well-done, grilled red meat increases the risk of colorectal adenomas.

Red meat or meat-cooking methods such as frying and doneness level have been associated with an increased risk of colorectal and other cancers. It is unclear whether it is red meat intake or the way it is cooked that is involved in the etiology of colorectal cancer. To address this issue, we developed an extensive food frequency questionnaire module that collects information on meat-cooking techniques as well as the level of doneness for individual meat items and used it in a study of colorectal adenomas, known precursors of colorectal cancer. A case-control study of colorectal adenomas was conducted at the National Naval Medical Center (Bethesda, MD) between April 1994 and September 1996. All cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy and histologically confirmed. Controls (n = 228) were screened with sigmoidoscopy and found not to have colorectal adenomas. The subjects completed a food frequency questionnaire and answered detailed questions on meat-cooking practices. We used frequency and portion size to estimate grams of meat consumed per day for total meat as well as for meat subgroups defined by cooking methods and doneness levels. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, total caloric intake, reason for screening (routine or other), and several established risk factors for colorectal adenomas or cancer, including the use of nonsteroidal anti-inflammatory drugs, physical activity, and pack-years of cigarette smoking. There was an increased risk of 11% per 10 g/day (or 2.5 oz/week) of reported red meat consumption (OR, 1.11; CI, 1.03-1.19). The increased risk was mainly associated with well-done/very well-done red meat, with an excess risk of 29% per 10 g/day (OR, 1.29; CI, 1.08-1.54) versus an excess of 10% per 10 g/day (OR, 1.10; CI, 0.96-1.26) for consumption of rare/medium red meat. High-temperature cooking methods were also associated with increased risk; 26% per 10 g/day (OR, 1.26; CI, 1.06-1.50) of grilled red meat and 15% per 10 g/day (OR, 1.15; CI, 0.97-1.36) of pan-fried red meat consumption. There was an increased risk of colorectal adenomas associated with higher intake of red meat, most of which was due to the subgroup of red meat that was cooked until well done/very well done and/or by high-temperature cooking techniques, such as grilling. These results are consistent with the hypothesis that carcinogenic compounds formed by high-temperature cooking techniques, such as heterocyclic amines and polycyclic aromatic hydrocarbons, may contribute to the risk of developing colorectal tumors.

Adenoma↗
PubMed1999

Increased incidence rates but no space-time clustering of childhood astrocytoma in Sweden, 1973-1992: a population-based study of pediatric brain tumors.

BACKGROUND: Incidence patterns, trends, and spatial and/or temporal clustering of childhood brain tumors were analyzed in the population-based national cancer registry of Sweden. METHODS: Temporal trends were analyzed by a logistic regression procedure in which the average annual percentages of change in incidence rates and the corresponding 95% confidence intervals (CIs) were calculated. Spatial and/or temporal clustering were investigated by using a geographic information system and analyzed with a modified version of the Knox test and a spatial scan statistic. RESULTS: Primary brain tumors in 1223 children ages 0-15 years were registered during 1973-1992. In 80% of cases, the tumor was classified as malignant. Conclusive histopathology was classified in 1142 cases. The age-adjusted incidence rate for all subtypes of brain tumors was 35.9 cases per million children, and for malignant brain tumors 28.6. A statistically significant increasing temporal trend was observed for the group of malignant brain tumors as a whole (P=0.0001) and the astrocytoma subgroup (P=0.0001). The annual average increases were 2.6% (95% CI=1.5-3.8) and 3.0%, respectively (95% CI=1.6-4.4). The increase in astrocytoma cases was significantly larger for girls than for boys (P=0.021) and was most striking for girls ages 6-15 years, with an annual average increase of 4.7%. Rates had not increased for the primitive neuroectodermal tumor (PNET)/medulloblastoma or ependymoma subgroups. The geographic distribution of astrocytoma cases was homogenous. No statistically significant space-time interaction or local clusters in space and/or time were found for astrocytomas only or when astrocytomas were grouped with PNETs/medulloblastomas and ependymomas. CONCLUSIONS: The results show statistically increased incidence rates of childhood astroglial tumors, predominantly for girls, in Sweden during the period 1973-1992, but no clustering in space or time.

Adolescent↗
PubMed1998

Fried, well-done red meat and risk of lung cancer in women (United States).

OBJECTIVE: Some epidemiological studies suggest that diets high in fat, saturated fat, or cholesterol are associated with increased risk of lung cancer. Since meat consumption is correlated with the intake of saturated fat and cholesterol, we investigated the role of meat intake and cooking practices in relation to lung cancer risk. METHODS: A population-based case-control study of both non-smoking and smoking women was conducted in Missouri. A 100-item food frequency questionnaire (FFQ) with detailed questions on meat consumption was completed by 593 cases and 623 frequency matched controls. We estimated quantity of meat eaten (grams/day) according to cooking method, and doneness level. Odds ratios (ORs) and 95% confidence intervals (C.I.s) were calculated using logistic regression. Multivariate models included age, packyears of smoking, body mass index (BMI, kg/m2), education, and intake of calories, fat, fruit/fruit juices, and vegetables. RESULTS: When comparing 90th and 10th percentiles, lung cancer risk increased for total meat consumption (OR = 1.6, C.I. 1.1-2.4), red meat (OR = 1.8, C.I., 1.2-2.7), well-done red meat (OR = 1.5, C.I.s, 1.1-2.1) and fried red meat (OR = 1.5, C.I., 1.1-2.0). The odds ratios for 5th vs. 1st quintiles using the categorical variable for well-done red meat and fried red meat were essentially the same as reported above; however, the increase in risk was associated mainly with the 5th quintile. The ORs for a 10-gram increase in consumption were, 1.04 for total meat, 1.06 for red meat, 1.08 for well done red meat, and 1.09 for fried red meat. CONCLUSIONS: Consumption of red meat, especially fried and/or well-done red meat, was associated with increased risk of lung cancer.

Adult↗
PubMed1998

Evaluating cluster alarms: a space-time scan statistic and brain cancer in Los Alamos, New Mexico.

OBJECTIVES: This article presents a space-time scan statistic, useful for evaluating space-time cluster alarms, and illustrates the method on a recent brain cancer cluster alarms in Los Alamos, NM. METHODS: The space-time scan statistic accounts for the preselection bias and multiple testing inherent in a cluster alarm. Confounders and time trends can be adjusted for. RESULTS: The observed excess of brain cancer in Los Alamos was not statistically significant. CONCLUSIONS: The space-time scan statistic is useful as a screening tool for evaluating which cluster alarms merit further investigation and which clusters are probably chance occurrences.

Brain Neoplasms↗
PubMed1998

An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: can we detect informative differences among individuals' proliferation measures amid the noise?

We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U. S. National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays. Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH). Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within-participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive. The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant.

Adult↗
PubMed1997

Breast cancer clusters in the northeast United States: a geographic analysis.

High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.

Breast Neoplasms↗