Biomedical subjects

K E Malone

Publications and source records attributed to K E Malone.

At least 37 records · Page 2Linked to original sources

PubMed1999

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood.

Findings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990-1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers.

Adolescent↗

PubMed1999

Breast cancer risk in young women and history of selected medical conditions.

BACKGROUND: Several common medical conditions are associated with altered hormone levels, and may thus plausibly influence breast cancer risk. Few studies have examined such relationships, and we utilized a population-based case-control study of young women in the US to examine breast cancer risk following a history of various medical conditions. Relationships between breast cancer and each medical condition examined are biologically plausible, and relevant in terms of public health. METHODS: The study included 2173 breast cancer cases and 1990 population-based controls from three areas of the US, under 55 years, who were administered a questionnaire including details of physician-diagnosed medical conditions. RESULTS: No significantly increased or decreased breast cancer risk was associated with a history of thyroid disease, gallbladder disease, colorectal polyps, diabetes, high blood pressure, high cholesterol or surgery for endometriosis. There was some evidence of an increased breast cancer risk associated with ovarian cysts among women who did not receive an oophorectomy (relative risk [RR] = 1.94, 95% CI: 1.0-3.9). Non-significant increases in breast cancer risk were observed following diagnoses of several other cancers, including thyroid cancer, basal cell carcinoma, Hodgkin's disease and malignant melanoma. CONCLUSIONS: To conclude, our generally null results from this large, population-based study support results from previous studies in providing reassurance that women with a history of several common medical conditions do not appear to be at an increased risk of breast cancer at a young age.

Adult↗

PubMed1999

Integrated designs for gene discovery and characterization.

Recent advances, including near completion of the human genome map, ever improving high-throughput technologies, and successes in discovering chronic disease-related genes, have stimulated the further development of genetic epidemiology. The primary mission of genetic epidemiology is to discover and characterize genes, whether independent of or interactive with environmental factors, that cause human diseases. To accomplish such a mission, genetic epidemiology needs to integrate both genetic and epidemiologic approaches. One of the challenges facing such an integrated approach is the identification of study designs that are efficient for both gene discovery and characterization. Because designs for gene discovery alone and designs for gene characterization alone have been elaborated in the other two panels, the focus of this paper is to describe those designs that may be useful for discovery and characterization jointly, including case-family and case-control-family designs. Examples of integrated designs are described, and studies of breast cancer conducted at the Fred Hutchinson Cancer Research Center are used for illustration. Finally, related analytic issues are also discussed.

Breast Neoplasms↗

PubMed1998

Electric blanket use and breast cancer risk among younger women.

To investigate whether use of electric blankets, one of the largest sources of electromagnetic field exposure in the home, is associated with the risk of female breast cancer, the authors analyzed data from a population-based US case-control study. The 2,199 case patients were under age 55 years and had been newly diagnosed with breast cancer between 1990 and 1992. The 2,009 controls were frequency-matched to cases by 5-year age group and geographic area. There was little or no risk associated with ever having used electric blankets, mattress pads, or heated water beds among women under age 45 years (adjusted odds ratio = 1.01, 95% confidence interval 0.86-1.18) or among women aged > or =45 years (adjusted odds ratio = 1.12, 95% confidence interval 0.87-1.43). There was no substantial variation in risk with duration of use; with whether the appliance was used only to warm the bed or used throughout the night; with menopausal status; or with the cases' hormone receptor status or stage of disease. Potential breast cancer risk factors that were associated with electric blanket use did not substantially confound the associations under investigation. These data do not support the hypothesis that electric blanket use increases breast cancer risk among women under age 55 years.

Adult↗

PubMed1998

BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history.

CONTEXT: Studies of high-risk families with multiple early-onset cases of breast cancer have been useful for assessing the type and spectrum of germline mutations on the BRCA1 gene, but do not provide guidance to women with modest family history profiles. Thus, studies of women from the general population are needed to determine the BRCA1 mutation frequency in women perceived to be at high risk, and to develop profiles of those most likely to be carriers. OBJECTIVE: To characterize frequency and spectrum of germline BRCA1 mutations in 2 categories of women identified via population-based studies hypothesized to be at increased risk of carrying such mutations: those diagnosed as having breast cancer before age 35 years and those diagnosed before age 45 years who have first-degree breast cancer family history. DESIGN: Study subjects were drawn from 2 population-based case-control studies of breast cancer in young women on the basis of their family history or their age of diagnosis. Cases were younger than 35 years or were younger than 45 years with first-degree family history at the time of breast cancer diagnosis and were ascertained via a population-based cancer registry, and controls (women without breast cancer) were identified via random-digit dialing. SETTING: Three counties in western Washington State. MAIN OUTCOME MEASURE: BRCA1 germline mutations in study subjects identified in DNA from peripheral blood lymphocytes by single-strand conformation polymorphism analysis using primer pairs that span the BRCA1 coding region and intron-exon boundaries. RESULTS: Of 193 women diagnosed as having breast cancer before age 35 years, none of whom were selected on the basis of family history status, 12 (6.2%, 95% confidence interval [CI], 3.2%-10.6%) had germline BRCA1 mutations. In 208 women diagnosed before age 45 years who had first-degree breast cancer family history, 15 (7.2%, 95% CI,4.1%-11.6%) had germline mutations in BRCA1. In both groups, there were variations in mutation frequency noted by age and by family history. Mutation frequency decreased with increasing age of diagnosis. Higher proportions of mutations were seen in cases with at least 1 relative diagnosed as having breast cancer before age 45 years, in cases with greater numbers of affected relatives, and those with ovarian cancer family history. Mutation frequency did not vary by bilateral breast cancer family history. No frameshift or nonsense mutations were observed in 71 control women with a first-degree family history, although missense changes of unknown significance were seen in cases and controls. CONCLUSIONS: Women with BRCA1 germline mutations lacked a common family history profile. Also, a large proportion of the women with a first-degree breast cancer family history and women diagnosed as having breast cancer before age 35 years did not carry germline BRCA1 mutations. Hence, while early-onset disease and a strong breast cancer family history may be useful guidelines for checking BRCA1 status, these findings on women drawn from the general population suggest that it may be difficult to develop BRCA1 mutation screening criteria among women with modest family history profiles.

Adult↗

PubMed1998

Diet during adolescence and risk of breast cancer among young women.

BACKGROUND: A variety of breast cancer risk factors pertain to a woman's adolescence and may be related to nutritional influences. We assessed risk of early-onset breast cancer related to diet during adolescence in a case-control study. METHODS: Study participants were accrued from the following three geographical regions covered by cancer registries: Atlanta, GA; Seattle/Puget Sound, WA; and central New Jersey. Case patients (n = 1647) were newly diagnosed with breast cancer, and control subjects (n = 1501) were identified by random-digit-dialing techniques. In an interview, each subject was asked to recall the frequency of consumption and portion size of 29 key food items at ages 12-13 years. Mothers of a subset of respondents completed questionnaires, and food groups were recalculated after removal of foods with poor agreement between mother and daughter. Logistic regression analyses were used to calculate odds ratios and 95% confidence intervals. RESULTS: When high versus low quartiles of consumption were compared, there was a suggestion of a reduced risk associated with high consumption of fruits and vegetables, although this finding was not statistically significant. Slight increases (of borderline statistical significance) in risk of breast cancer were found for intake of chicken or high-fat meat. Intake of animal fat, high-fat foods, high-fat snacks and desserts, or dairy products during adolescence had no apparent influence on breast cancer risk. Removal of foods suspected to be poorly recalled by the daughters did not change any of the risk estimates. CONCLUSION: These data do not provide evidence for a strong influence of dietary intakes during adolescence on risk of early-onset breast cancer.

Adolescent↗

PubMed1998

Validity and reliability of subject and mother reporting of perinatal factors.

The authors used data from a population-based case-control study of breast cancer in women aged < or = 44 years (cases, n = 975; controls, n = 866) conducted between 1994 and 1996 in three counties of western Washington state to assess the validity and reliability of reported perinatal factors. For a sample of participants, exposure information from self-administered questionnaires was validated with information from birth certificates (cases, n = 378; controls, n = 283). Detailed information regarding perinatal characteristics of their daughters was also collected from subjects' mothers (case mothers, n = 510; control mothers, n = 436) to assess the reliability of subjects' reporting of these events. Although reporting of birth weight by subjects (cases, r = 0.83; controls, r = 0.80) and their mothers (case mothers, r = 0.89; control mothers, r = 0.84) was highly correlated with the birth certificates, there was differential measurement error by subjects; cases reported birth weight accurately on average, but controls tended to underestimate their birth weight. Agreement between the subject and mother report was excellent for birth weight (cases, r = 0.85; controls, r = 0.87) and good for other perinatal factors, but birth order and maternal diethylstilbestrol use were underreported among cases and reported accurately among controls. Differential measurement error of birth weight by case-control status resulted in biased odds ratios for breast cancer risk.

Birth Weight↗

PubMed1998

Cigarette smoking and breast cancer risk among young women (United States).

OBJECTIVES: To evaluate whether heavy cigarette smoking as a teenager or long-term smoking increases breast cancer risk or, alternatively, whether smoking acts as an anti-estrogen and reduces risk. METHODS: Data from a multi-center, population-based, case-control study among women under age 55 were analyzed. RESULTS: Among women under age 45, there was a modest inverse relation with current (OR = 0.82, 95% CI = 0.67, 1.01) but not past (OR = 0.99, 95% CI = 0.81, 1.21) smoking. Odds ratios were decreased for current smokers who began at an early age (0.59 for < or = 15, 95% CI = 0.41, 0.85) or continued for long periods of time (0.70 for >21 years, 95% CI = 0.52, 0.94). In subgroup analyses, reduced odds ratios were observed among current smokers who were ever users of oral contraceptives (0.79, 95% CI = 0.63, 0.98), were in the lowest quartile of adult body size (0.53, 95% CI = 0.34, 0.81), or never or infrequently drank alcohol (0.68, 95% CI = 0.47, 0.98). Among women ages 45-54, there was little evidence for an association with smoking. CONCLUSIONS: These results suggest that breast cancer risk among women under age 45 may be reduced among current smokers who began smoking at an early age, or long-term smokers, but require confirmation from other studies.

Adolescent↗

PubMed1998

Maternal factors and breast cancer risk among young women.

The results from previous studies have provided evidence to support the hypothesised association between intrauterine oestrogen exposure and subsequent risk of breast cancer. Information has not been available to study this relationship for several perinatal factors thought to be related to pregnancy oestrogen levels. Data collected from the mothers of women in two population-based case-control studies of breast cancer in women under the age of 45 years (510 case mothers, 436 control mothers) who were diagnosed between 1983 and 1992 in three western Washington counties were used to investigate further the relationship between intrauterine oestrogen exposure and risk of breast cancer. A pregnancy weight gain of 25-34 pounds was associated with breast cancer risk (odds ratio [OR] = 1.5; 95% confidence interval [CI] 1.1, 2.0); however, women whose mothers gained 35 pounds or more were not at increased risk. Use of antiemetic medication in women with any nausea and vomiting (OR = 2.9; 95% CI 1.1, 8.1) and use of diethylstilboestrol (DES) (OR = 2.3; 95% CI 0.8, 6.4) appeared to be positively associated with breast cancer risk. The results from this study provide limited support for the hypothesis that in utero oestrogen exposure may be related to subsequent breast cancer risk among young women.

Adult↗

PubMed1998

Pregnancy characteristics and maternal risk of breast cancer.

In a population-based case-control study of parous women less than 45 years of age, we evaluated the relations of various pregnancy characteristics to maternal breast cancer risk. Cases (N = 1,239) diagnosed with in situ or invasive breast cancer from 1990 to 1992 in Atlanta, GA, Seattle/Puget Sound, WA, and five counties in central New Jersey, and population controls (N = 1,166) identified by random-digit dialing, were interviewed regarding the details of their pregnancies. We used logistic regression to estimate relative risks (RR) and 95% confidence intervals (CI) and to adjust for breast cancer risk factors. Women who reported nausea or vomiting in their first pregnancy had a slightly lower risk of breast cancer (RR = 0.87; 95% CI = 0.72-1.0). We found no strong or consistent associations for maternal risk related to gestational length, pregnancy weight gain, gestational diabetes, pregnancy hypertension, or gender of the offspring, although we found some evidence for reductions in risk for toxemia (RR = 0.81; 95% CI = 0.61-1.1) and specific sex (RR for female twins vs singletons = 0.48; 95% CI = 0.20-1.3) and timing characteristics of twinning. Overall, these data provide little support for the hypothesis that pregnancy hormone levels are associated with subsequent maternal risk of breast cancer in young women.

Adult↗

PubMed1997

Characteristics of women with and without breast augmentation.

OBJECTIVE: To compare selected characteristics of women with and without augmentation mammaplasty to identify differences between these 2 groups of women. DESIGN AND STUDY PARTICIPANTS: White women identified as controls in previously conducted population-based, case-control studies formed the study population for the present cross-sectional analysis (N=3570). MAIN OUTCOME MEASURE: Interview information on selected characteristics was compared between women who had received augmentation mammaplasty (n=80) and other women (n=3490) using the prevalence odds ratio (pOR) as the measure of association. RESULTS: Women with breast implants were more likely to drink a greater average number of alcoholic drinks per week (for > or =7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval [CI]=1.5-5.5), be younger at first pregnancy (for age <20 years vs age 20-29 years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age <20 years vs age 20-29 years: pOR=1.9, 95% C1=1.1-3.3), have a history of terminated pregnancies (for > or =1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4), have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual partners (for > or =14 partners vs < or =4 partners: pOR=8.9, 95% CI=3.1-25.5) than other women. A history of smoking, lactation, high blood pressure, or thyroid disorders, as well as the number of pregnancies, full-term births, or miscarriages, differed little between women with and without implants. Women with breast augmentation were much less likely to be heavy than other women (for > or =74 kg vs <56 kg: pOR=0.1, 95% CI=0.03-0.3). CONCLUSION: The differences we found between women with and without breast implants suggest that consideration and evaluation of confounding factors in future studies will help to clarify some of the long-term health consequences of having breast implants.

Adult↗

PubMed1997

Modification of oral contraceptive relationships on breast cancer risk by selected factors among younger women.

In a case-control study of 1647 breast cancer cases and 1501 population controls under 45 years of age, potential modifying effects of other risk factors on the relationship of oral contraceptives to breast cancer were examined. Among the total series of study subjects, the relationship of extended pill usage was greater in non-white than white women. Oral contraceptive associations, however, did not appear to be substantially modified by other risk factors, including parity, body size, or family history of breast cancer (apart from a somewhat enhanced relationship among subjects who reported a sister with breast cancer. Further, oral contraceptive relationships did not vary by a history of benign breast disease, although the majority of subjects began pill usage prior to the development of benign breast disease. Among the women under the age of 35, in whom oral contraceptive relationships were heightened (over a twofold excess risk for use of 5 years or longer), pill relationships were less modified by race than in the total series. Although among these younger subjects there was no effect of pill usage in heavy women, and an enhanced relationship among heavier consumers of alcoholic beverages, these interactive effects were not statistically significant. The findings of this study generally support no substantial variation in oral contraceptive relationships by other breast cancer risk factors, although some further attention might be warranted regarding possible modifying effects of race, body size, type of relative with breast cancer, and alcohol consumption.

Adult↗

PubMed1997

Leisure-time physical activity in relation to breast cancer among young women (Washington, United States).

It has been hypothesized that women who participate in vigorous physical activity may have lower risk of breast cancer due to lower lifetime exposure to ovarian hormones. A population-based case-control study was conducted to investigate the association between leisure-time physical activity and risk of breast cancer among women aged 21 to 45 years. Cases were 747 women diagnosed with invasive breast cancer between 1983 and 1990 in three counties of western Washington state (United States), and were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry. Controls were 961 women selected from the same area by random-digit telephone dialing. Physical activity was assessed through personal interview, with questions on frequency and duration of each type of recreational activity during the two-year period immediately prior to reference data (date of diagnosis for cases and a comparable assigned date for controls) and between ages 12 and 21. For the two-year time period before diagnosis, there was no association with frequency of activity (age-adjusted odds ratio [OR] = 0.93, 95 percent confidence interval [CI] = 0.71-1.22 for four or more episodes per week cf none), total hours spent in physical activity (age-adjusted OR = 0.92, CI = 0.71-1.22 for four or more hours per week cf none) or MET (metabolic equivalent energy expenditure unit) (age-adjusted OR = 0.95, CI = 0.73-1.23 for 18 or more METs per week of none), nor any trend is risk with increasing activity levels. Similarly, there was no association between leisure activity during adolescence and breast cancer risk. These results were not confounded further by body mass index (wt/ht2), age at menarche, age at first full-term pregnancy, parity, family history of breast cancer, or other measured health behaviors. Our findings do not support a protective effect of leisure-time physical activity either in the adolescent years or in adulthood on breast cancer in young women.

Adult↗

PubMed1997

Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients.

Mutations in certain genes that regulate the cell cycle, such as p16 and p53, are frequently found in human cancers. However, tumor-specific mutations are uncommon in genes encoding cyclin E and the CDK inhibitor p27Kip1, two cell-cycle regulators that are also thought to contribute to tumor progression. It is now known that levels of both cyclin E and p27 can be controlled by posttranscriptional mechanisms, indicating that expression of these proteins can be altered by means other than simply mutation of their respective genes. Thus, changes in p27 and cyclin E protein levels in tumors might be more common than previously anticipated and may be indicators of tumor behavior.

Adult↗

PubMed1997

Prenatal and perinatal risk factors for breast cancer in young women.

There is increasing interest in the role of early life exposures in breast carcinogenesis, especially estrogen exposure in utero. Estrogen levels during pregnancy may be higher in twin pregnancies and among older women and slightly lower among smokers. We analyzed early life risk factors in a population-based case-control study in the United States of 2,202 breast cancer cases and 2,009 controls under age 55 years. Twins were at an increased risk of breast cancer compared with singletons (relative risk = 1.62; 95% confidence interval = 1.0-2.7), particularly women with a twin brother (relative risk = 2.06), a finding consistent with the observation of high estrogen levels in dizygotic twin pregnancies. Little association was seen between maternal age at birth and breast cancer risk. We carried out further analyses for 534 cases and 497 controls under age 45 years, using data from a questionnaire completed by their mothers relating to the daughters' early life exposures. There was no evidence of an effect of smoking or diethylstilbestrol exposure during pregnancy on daughters' breast cancer risk. A reduced breast cancer risk was seen among women who had been breastfed (relative risk = 0.74; 95% confidence interval = 0.6-1.0). These findings indicate some effect of early life exposures on breast cancer risk, although the role of estrogen exposure may be less central than previously suggested.

Adult↗

PubMed1997

Alcohol consumption and breast cancer risk among women under age 45 years.

In a population-based case-control study of women younger than 45 years of age, we obtained a detailed lifetime history of alcohol use to evaluate the effects of drinking during different periods of life in relation to breast cancer risk. This analysis focused on interviews obtained from 1,645 cases and 1,497 controls. Breast cancer risk was not influenced by drinking during the teenage years or early adulthood. Contemporary drinking (that is, average intake during the recent 5-year interval) was directly associated with risk, but the adverse effect of recent drinking was restricted to women who consumed > or = 14 drinks per week [relative risk (RR) = 1.7; 95% confidence interval (CI) = 1.2-2.5]. The effect of alcohol was most pronounced among women with advanced disease. Compared with nondrinkers, the risk estimate associated with recent consumption of > or = 14 drinks per week was 2.4 (95% CI = 1.6-3.8) for women with regional/distant disease. Our data add support to the accumulating evidence that alcohol consumption is associated with increased risk of breast cancer and further indicate that alcohol acts at a late stage in breast carcinogenesis.

Adult↗

PubMed1997

Age when maximum height is reached as a risk factor for breast cancer among young U.S. women.

We evaluated height as a potential risk factor for breast cancer in a case-control study of 747 young women diagnosed with invasive breast cancer before age 46 years and 961 control subjects recruited by random digit dialing. We found that total height attained did not affect a woman's risk of the disease. The age when a women reached her maximum height, however, was a risk factor for breast cancer. There was a trend of decreasing risk of breast cancer in relation to increasing age of height attainment, culminating in a 30% reduction in the risk of breast cancer for women who reached their maximum height when they were 18 years or older compared with women who reached their maximum height when they were 13 years old or less (odds ratio = 0.7; 95% confidence interval = 0.5-1.0). Although the age at menarche was correlated with the age at maximum height, the effect of age at maximum height persisted after adjustment for age at menarche. Previous studies have reported that age at menarche is an important determinant of risk, but this study indicates that age when maximum height is reached may be another, and possibly more important, landmark of puberty that is related to breast cancer risk. The physiologic basis for this claim may lie in the influence on breast development of exposure to growth hormone and insulin-like growth factor during puberty, and on a decreased time between the end of puberty and a woman's first livebirth, both of which are believed to affect a woman's risk of breast cancer.

Adolescent↗

PubMed1996

Family history and survival of young women with invasive breast carcinoma.

BACKGROUND: This study investigates whether a positive family history of breast carcinoma is associated with improved survival after invasive breast carcinoma among women ages 21 through 45. METHODS: Subjects were 733 nonadopted women born after 1944 who were diagnosed with primary invasive breast carcinoma between January 1983 and April 1990 while residing in the metropolitan Seattle area and who provided information on family history of breast carcinoma. Information on clinical characteristics and survival was obtained from a population-based cancer registry. Subjects were followed for survival through 1994. Cox proportional hazards models were used to estimate the relative risk (RR) of dying in relation to family history of breast carcinoma, adjusting for selected clinical characteristics, age and year of diagnosis, and prior mammograms. RESULTS: The risk of dying among women with a first-degree family history of breast carcinoma was half that of women with no family history of breast carcinoma (RR = 0.5%; 95% confidence interval [CI], 0.3-0.9). There was no evidence of a reduction in the risk of dying among women with only a second-degree family history of breast carcinoma (RR = 1; 95% CI, 0.6-1.4). These associations were adjusted for age and year of diagnosis, stage of disease, tumor size, bilaterality, and mammogram history. These findings were not further influenced by adjustment for initial treatment or the numbers and ages of relatives at risk for breast carcinoma. CONCLUSIONS: Compared with women with neither a first- nor second-degree family history of breast carcinoma, the authors found that women who had a first-degree family history experienced increased survival. This finding did not appear to be attributable to differences in screening or treatment. To the extent that this difference is attributable to underlying biologic mechanisms, new insights into the natural history and treatment of breast carcinoma could result. Future studies should investigate whether specific susceptibility genes are associated with differential survival from breast carcinoma.

Adult↗