How much physical activity do we need to maintain health and prevent disease? Different diseases--different mechanisms.
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Biomedical subjects
Publications and source records attributed to M L Slattery.
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OBJECTIVE: To estimate the relative risks and population attributable risks of ovarian cancer associated with family histories of cancer at several sites. METHODS: A matched case-control analytic study (662 cases, 2647 controls), employing the Utah Population Database, a genealogy of approximately 1 million individuals linked to cancer incidence data from the Utah Cancer Registry. Family history was assessed using kinship order and a kinship-weighted familial standardized incidence ratio statistic. RESULTS: Family histories of ovarian, uterine, breast, and pancreatic cancer were significantly associated with increased risk of ovarian cancer. The relative risk of ovarian cancer was 4.31 (95% confidence interval [CI], 2.35 to 7.90) for women with a first-degree relative with ovarian cancer, 2.12 (95% CI, 1.19 to 3.78) for women with an affected second-degree relative, and 1.48 (95% CI, 0.98 to 2.24) for women with an affected third-degree relative. The odds ratio (OR) was 2.06 (95% CI, 1.44 to 2.93) for those with the highest familial standardized incidence ratio. No age differences were observed between cases with and without a family history of ovarian cancer. There was substantial heterogeneity of family history effects by cell type. Increased parity was not protective among women with a strong family history of cancer at the sites studied (OR, 1.11; 95% CI, 0.38 to 3.26), although it was protective among women without a family history of these cancers (OR, 0.29; 95% CI, 0.11 to 0.62). CONCLUSIONS: The risk of ovarian cancer was substantially increased among women with family histories of ovarian, uterine, pancreatic, and, to a lesser degree, breast cancer. Among women with family histories of any of these cancers, the risk of ovarian cancer is not diminished by high parity.
The Utah (United States) Population Database was used to evaluate the associations between reproductive factors and colon cancer risk and the impact that family history, age at diagnosis, and tumor site have on these associations. From the cohort of (White) women in the database, all first-primary cases of colon cancer (n = 819) and controls who had complete fertility information (n = 3,202) were examined. The majority of tumors (68.6 percent) among women diagnosed at age 64 years or less were in the distal segment of the colon, while among women 65 or older, the majority of tumors (55.7 percent) were proximal. Women diagnosed before age 65 had a lower risk of colon cancer with increasing numbers of liveborn children (odds ratio [OR] = 0.6, 95 percent confidence interval [CI] = 0.3-0.9 for women with five or more children compared with women with one or two children). A long interval between first and second births (first birth-interval) was associated with increased risk of tumors in the distal segment of the colon (OR = 1.4, CI = 1.0-2.0) and among women diagnosed before age 65 (OR = 1.6, CI = 1.0-2.5); a longer, average birth-interval was associated with increased risk of proximal tumors (OR = 1.5, CI = 1.1-2.1).(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: The purpose of this study was to assess risk of developing multiple primaries after a diagnosis of colon cancer and to determine the impact that having a family history of cancer has on cancer risk. METHODS: Data from the Utah Cancer Registry and the Utah Population Database were used. A cohort of 2,236 first primary colon cancers were observed for the subsequent development of additional primary cancers. RESULTS: We observed a greater than expected incidence of colon, rectal, and pancreatic cancers among the cohort. The standardized incidence ratios were 2.77 (95 percent confidence interval (CI), 2.07-3.70), 2.26 (95 percent CI, 1.34-3.81), and 2.38 (95 percent CI, 1.32-4.30), respectively. Having a family history of colon or rectal cancer did not greatly influence risk of having a multiple primary. However, there was a trend toward increased risk of pancreatic cancer (hazard rate ratios, 1.99; 95 percent CI, 0.67-5.90) and bladder cancer (hazard rate ratios, 2.35; 95 percent CI, 0.77-7.18) among patients with a family history of rectal cancer. We also observed that risk of uterine cancer in the cohort was positively associated with family history of uterine cancer, risk of breast cancer was positively associated with family history of breast cancer, and risk of prostate cancer was positively associated with family history of prostate cancer. CONCLUSIONS: People with colon cancer are at a greater risk of developing colon, rectal, and possibly pancreatic cancer. Although a family history of colon or rectal cancer did not have a large impact on developing other cancers, a family history of other primary cancers did influence risk of other cancers.
BACKGROUND & AIMS: Microsatellite instability is a property of most tumors occurring in the context of hereditary nonpolyposis colon cancer. Instability also occurs in 10%-15% of apparently sporadic colorectal cancers, and it has been hypothesized that this instability may indicate a genetic predisposition to colonic cancer. This study evaluated whether there is a clinically useful association between colon cancer instability and a family history of cancer. METHODS: Colon cancer cases (n = 188) from a population-based study were evaluated for microsatellite instability with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics. RESULTS: Microsatellite instability was found in 16.5% of tumors. It was predominantly a feature of right-sided tumors (P = 0.003) and was associated with the youngest and oldest ages at diagnosis (P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-S-transferase mu 1 null genotype. CONCLUSIONS: Although some very small, and as yet undefined, proportion of colon cancer may be caused by inherited mutations leading to microsatellite instability, tumoral instability by itself is not a marker for familiality and should not be considered as evidence for an inherited syndrome.
In this study we assessed the reliability of recall of physical activity. Study participants were members of the Coronary Artery Risk Development in Young Adult Study (CARDIA) cohort who reported physical activity at each CARDIA examination. In this study, we asked 81 participants to recall activity patterns for the year prior to 2 to 3 years ago so that we could compare recalled activity patterns to those reported 2 to 3 years ago (labeled as "distantly recalled") as well as to activity patterns reported at the other CARDIA examinations. We found that distantly recalled physical activity patterns were highly correlated with those reported at the time of the examination where they were obtained (vigorous activity r = 0.84, moderate activity r = 0.64, and total activity r = 0.81). Distantly recalled activity was less highly associated with activity reported currently (vigorous activity r = 0.57, moderate activity r = 0.45, total activity r = 0.59). The activity recalled the best was jogging or running (r = 0.76) and the activity with the poorest recall was racket sports (r = 0.53). Distantly recalled physical activity also was related to resting pulse rate obtained during the time period of the recalled activity (r = -0.21). These findings suggest that people can recall activity patterns of several years ago with high reliability.
Response rates are an important component of epidemiologic research. The purposes of this study are (a) to evaluate how response rates are defined and calculated for control subjects in epidemiologic case-control studies, and (b) to explore factors that may impact response in epidemiologic studies. Our results show that the method of control subject selection has an impact on study response. Gender of respondent does not appear to impact response rates. However, response rates are generally worse for individuals less than 45 years old. Methods used to calculate response have a great impact on "response rate"; therefore, it is important for researchers to define exactly what the reported response rates represent and how they are derived so that data can be interpreted appropriately.
It is generally believed that breast cancer is a multistage process and that multiple and varying genetic events occur on the pathway to disease. We hypothesize that disease heterogeneity has an impact on our ability to identify risk factors. If a genetic alteration occurred in 50% of cases and a risk factor was associated only with that specific alteration, a risk estimate of 1.6 would be detected rather than the true risk estimate of 2.5 if analyses had been limited to those cases with the genetic alteration. Based on the literature we know that many genetic alterations occur in less than 50% of breast tumors. Thus, if environmental factors are related to some, but not all genetic alterations, we are decreasing our ability to identify potentially important risk factors. We therefore hypothesize that identification of dietary factors associated with breast cancer has been hampered by our inability to identify and capture the unique disease pathways which exist and contribute to the heterogeneity of common cancers such as breast cancer.
OBJECTIVE: To determine if dietary antioxidants play a role in preventing coronary heart disease (CHD) by having an impact on lipid levels. METHODS: Data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to assess the associations of reported intake of vitamins A, C, E and beta carotene, and their use in supplements, with lipid levels in a black and white, healthy adult (18 to 30 years of age at the baseline examination) population. RESULTS: After adjusting for age, education level, physical activity, body size, alcohol consumption and caloric intake, vitamin A, beta carotene, and vitamin C (white women) intake were directly associated with HDL-cholesterol levels among women who smoked cigarettes, with the strongest associations being observed for white women. Black men who took supplements of vitamins A and C and did not smoke cigarettes had significantly higher HDL-cholesterol levels compared to those in the lowest levels of dietary intake. Although vitamin E was associated with higher levels of HDL-cholesterol, the association was only of borderline significance among white men who smoked cigarettes (p = 0.06). We did not observe any consistent associations between antioxidants and other plasma lipids, including total cholesterol, LDL-cholesterol, or triglycerides. CONCLUSIONS: We conclude that dietary antioxidants are associated with HDL-cholesterol levels in some subsets of the population, although these associations may be operating in conjunction with other lifestyle behaviors.
BACKGROUND: The impact of family history of colon cancer on survival after diagnosis with colon cancer is generally unknown. It is possible that family history is indicative of a genetically inherited form of disease which may alter survival. METHODS: The Utah Population Database was used to evaluate survival after diagnosis with colon cancer among 2236 first primary colon cancer cases. This database includes detailed information about family history and is linked to the Utah Cancer Registry to obtain tumour information. RESULTS: Stage at diagnosis was the primary factor associated with death from all causes and from colon cancer. An older age at diagnosis, being female, and having a tumour in the ascending segment of the colon also were associated with poorer survival, although after adjusting for stage at diagnosis these associations disappeared. Having a family history of colon cancer had little impact on survival patterns although there were suggestions that men who were diagnosed at age < or = 55 were more likely to die from all causes as well as colon cancer if they had a sibling with colon cancer (hazard rate ratio [HRR] 2.50, 95% confidence interval [CI]: 1.03-6.10) relative to men > 55 without a sibling with colon cancer. CONCLUSIONS: From these data it appears that the major factor which increases survival is being diagnosed at an early stage of disease. These data also suggest that younger men who have a sibling with colon cancer may have a different form of colon cancer which increases their risk of dying.
We used data from a population-based case-control study conducted in Utah from 1984 to 1987 to determine whether the low incidence of cervical carcinoma in Mormon women can be explained by adherence to their religious teachings, which proscribe smoking and extramarital sexual relations. Mormon women had substantially lower risk for cervical carcinoma than non-Mormons [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.28-0.54]; this low risk was confined to those who attended church frequently. The protective effect disappeared after controlling for differences in age, sexual behavior, and smoking (OR = 1.22; 95% CI = 0.80-1.87).
In this paper, the authors present an objective system to evaluate interviewer performance for use in epidemiologic studies. With this quality control system, all study interviews are audio-taped, and a random sample of interviews are coded according to interviewer behaviors, such as whether the interviewer asked the questions exactly as written and used the probes appropriately. With the use of data obtained from a large case-control study of colon cancer, the authors observed that 94.2% of all questions were asked in the same manner by all interviewers and that 89.5% of all probing behaviors were appropriate. They show that questions that required additional interviewer behaviors were more likely to result in variation in response that can be attributed to the interviewer. These findings have implications for study design and interpretation of study results. From simulations, the authors have estimated the impact of uncorrected interviewer variability on study power and ability to detect disease associations. Uncorrected interviewer variability could decrease study power from 84% to 56%. From simulations, the authors observed that odds ratios could be biased downward from 1.8 to 1.3. These findings illustrate the importance of using a continuous quality control program in epidemiologic research.
BACKGROUND: Family history of colon cancer has been shown to be related to the risk of developing colon cancer. The impact that a comprehensive family history of colon or other cancers has on the risk of colon cancer has not been thoroughly studied. PURPOSE: The purpose of this study was to assess the risk of developing colon cancer associated with having a family history of colon, rectal, breast, ovarian, endometrial, or prostate cancer. METHODS: A case-control study was conducted using data from the Utah Population Database. Case patients had first primary colon cancers (n = 2543). Three control subjects per case were individually matched to case patients on year of birth, place of birth, marital status, and sex. RESULTS: Those case patients with the highest familial standardized incidence ratio were at an increased risk of developing colon cancer (for men, odds ratio [OR] = 2.51 and 95% confidence interval [CI] = 1.88-3.29; for women, OR = 2.90 and 95% CI = 2.17-3.82). A second- or third-degree relative with colon cancer increased risk from 25% to 52%. Risk associated with family history was greater in those patients diagnosed before age 50 (for men, OR = 3.61 and for women, OR = 7.18) than in those diagnosed at 50 or more years of age (for men, OR = 2.44 and for women, OR = 2.73). The risk associated with a family history of colon cancer was greatest for the distal segment of the colon. Women were at an increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.59; 95% CI = 1.25-2.03), uterine (OR = 1.50; 95% CI = 0.99-2.26), ovarian (OR = 1.63; 95% CI = 1.41-1.89), or prostate (OR = 1.49; 95% CI = 1.21-1.82) cancer; men were at increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.30; 95% CI = 1.02-1.66), uterine (OR = 1.96; 95% CI = 1.34-2.87), or ovarian (OR = 1.59; 95% CI = 0.90-2.81) cancer. CONCLUSIONS: These findings support previous observations that people with a family history of colon cancer are at increased risk of colon cancer. Those with a second- or third-degree relative with colon cancer or a first-degree relative with breast, ovarian, uterine, or prostate cancer also have an increased risk of developing colon cancer. IMPLICATIONS: These data support the recommendations that individuals who have a first-degree, and possibly a second- or third-degree, relative with colon cancer should have regular screening for colon cancer.
Data from two population-based case-control studies were used to investigate the effect of age on colon cancer risk. Dietary intake data were assessed from a study conducted in Utah (United States) between 1979 and 1983; reproductive data were assessed from a study conducted in Adelaide (Australia) between 1979 and 1980. Data from both studies were assessed for their impact on those less than 65 years of age and those 65 or more years of age. Intake of energy, fat, and protein had a greater impact on risk among older men than among younger men. Risk estimates for the upper quartile of intake relative to the lowest quartile of intake were 8.5 (95 percent confidence interval [CI] = 1.7-43.0) for energy, 8.2 (CI = 1.6-41.3) for protein, and 7.2 (CI = 1.6-31.4) for total fat for older men, while comparable risk estimates were 2.4 (CI = 0.6-9.1) for energy, 3.0 (CI = 0.7-13.6) for protein, and 1.9 (CI = 0.5-7.1) for total fat among younger men. Similar trends were seen for older women for energy and protein. beta-carotene decreased colon cancer risk among younger men (odds ratio [OR] = 0.4, CI = 0.1-1.2) and women (OR = 0.1, CI = 0.1-0.5), although not among older men (OR = 1.2, CI = 0.3-4.9) and women (OR = 1.9, CI = 0.6-64). Calcium decreased risk of colon cancer among older men (OR = 0.1, CI = < 0.1-0.8) and younger women (OR = 0.2, CI = < 0.1-0.7).(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To describe methods used to computerize the diet history questionnaire developed for the Coronary Artery Risk Factor Development in Young Adult (CARDIA) study and to describe quality-control procedures used in conjunction with dietary assessment. DESIGN: The computerized diet history is being used in a case-control study. Because of the computerized nature of the questionnaire, we developed quality-control procedures that incorporate listening to an audiotape of the interview while visually reviewing recorded data. SETTING: Three centers involved in a population-based epidemiologic study of colon cancer. SUBJECTS: Men and women between the ages of 30 and 79 years. RESULTS: Quality-control results showed that 100% of the computerized forms would be free of errors if the data were subjected to visual review only. Probing errors, which accounted for 47.3% of all errors, were the most commonly encountered errors. In probing errors the interviewer did not probe in a nondirective manner, or the interviewer failed to verify responses that might be considered questionable. APPLICATIONS: The CARDIA diet history was computerized for use in epidemiologic studies of the association between diet and disease. Review of the audiotapes of the interviews showed that most errors made in obtaining a dietary assessment were not detectable from visual review of the data. Although the quality-control procedures were developed for a computerized diet history questionnaire, they are applicable to other dietary assessment methods.
Data on dietary intake were collected in the Coronary Artery Risk Development in Young Adults (CARDIA) Study at the baseline examination in 1985-86 and again at the second examination 2 years later. At baseline, a diet history questionnaire developed for the CARDIA study was used; at the second exam the NCI (Block) food frequency questionnaire was used. The purpose of the present report is to compare the estimated nutrient intakes obtained with the two instruments; to compare correlations of nutrient intakes obtained at the two exams with those observed for other lifestyle and physiological variables also measured 2 years apart; and to assess ability to test hypotheses relating 2-year changes in risk factors to between-exam differences in reported nutrient intakes. Mean levels of reported intake were generally greater for both blacks and whites on the CARDIA diet history than on the Block food frequency. Rank order correlations of reported nutrient intakes between the two questionnaires indicated greater consistency between instruments for whites (r's ranging between 0.35 and 0.52) than for blacks (r's ranging between 0.29 and 0.45). Correlations over time for nutrients were smaller than those observed for body size measures and lipid levels but were similar in magnitude to those for blood pressure, physical activity, and life events. At both exams, total caloric intake was positively associated with physical activity (range of r's for CARDIA were 0.07 for white women to 0.23 for black men, the range of r's for Block were 0.06 for women to 0.11 for white men). Using data from the two examinations, 2-year changes in total plasma cholesterol were significantly related to 2 year changes in Keys scores. The results of this comparison are useful in that they show similarities and differences between two instruments developed to gather dietary intake data. The study also illustrates the need to monitor young adults during a time when rapid changes occur in many lifestyle and physiologic factors.
The waist-to-hip circumference ratio (WHR), as an indicator of body fat distribution is related to several clinical diseases. Whether one can reduce this ratio with weight loss is still unconfirmed and may differ between sexes. The degree to which WHR changes with weight gain is also unclear. Changes in waist and hip circumferences and WHR accompanying changes in weight over 5 years were examined in 3,753 black and white men and women initially ages 18-30. Those who gained weight increased their WHR and in most cases those whose weight remained stable increased their WHR. Those who gained the most weight had the greatest increases in WHR. Men had greater increases in WHR per kg weight gain than women. In general, weight loss was accompanied by a decrease in the WHR. However, in those whose initial WHR was below the median, weight loss was associated with an increase in WHR. Smokers and black males also had increases in WHR with weight losses up to 4.9 kg.
OBJECTIVE: The purpose of this study is to assess the impact of family history on the risk of developing breast cancer. DESIGN: A case-control study design was used. SETTING: To provide a comprehensive assessment of family history risk, we used the Utah Population Database, a linked database compiled of genealogy data of the descendants of Mormon pioneer families, cancer data from the Utah Cancer Registry, and mortality data from the Utah Department of Vital Statistics. PATIENTS: All women diagnosed with breast cancer who were in the genealogy database and the Utah Cancer Registry were included. Controls were women selected from the genealogy, who like cases had no record of previous cancer. They were matched to the cases by age and place of birth. OUTCOME: Several definitions of family history were used. The total familial risk variable, developed to work effectively in the Utah Genealogy Database, accounts for all family members, their degree of relatedness to the case, and the amount of time they were observed for possible cancer diagnosis. RESULTS: A threefold increase in risk, estimated by the odds ratio (OR), of breast cancer among those with the highest family history score (6% of cases) was observed when compared with those with the lowest family history score. The OR for women with a first-degree relative with breast cancer was 2.45 (95% confidence interval [CI], 1.84 to 3.06). If the nearest relative was a second-degree relative, the OR was 1.82 (95% CI, 1.39 to 2.24); if the nearest relative was a third-degree relative, the OR was 1.35 (95% CI, 1.07 to 1.64). A slightly greater risk was observed if the first-degree relative was a woman's mother (OR, 2.44; 95% CI, 1.77 to 3.42) rather than a sister (OR, 2.01; 95% CI, 1.66 to 2.43). Among subjects diagnosed before the age of 50 years, the disease experience of relatives prior to age 50 was most important, while for older subjects the experience of relatives of all ages was of roughly equal importance. Women who developed contralateral breast cancer within 3 years of initial diagnosis were nearly 10 times as likely as women without breast cancer to have a first-degree relative with breast cancer. Based on the risk estimates in this study, we have estimated that approximately 17% to 19% of breast cancer in the population could be attributed to family history. Women who had a first-degree relative with colon cancer had a 30% increased risk of breast cancer. CONCLUSIONS: In this study population, women with a family history of breast cancer, even if the nearest relative with breast cancer is a third-degree relative, are at increased risk of the disease.