Biomedical subjects
Publications and source records attributed to J A Baron.
The purpose of this study was to determine the hemodynamic and electrophysiologic effects of acute chocolate, and hence theobromine, ingestion on the hearts of young adults. Theobromine was not found to have any cardiovascular effects on subjects in this study.
A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.
BACKGROUND: Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we examined the endometrial cancer risk associated with combined estrogen-progestin regimens currently in use, since the safety profiles of these regimens have not been clearly defined. METHODS: We conducted a nationwide population-based, case-control study in Sweden of postmenopausal women aged 50-74 years. We collected information on use of hormone replacement from 709 case patients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as estimates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens. RESULTS: Treatment with estrogens alone was associated with a marked duration- and dose-dependent increase in the relative risk of endometrial cancer. Five or more years of treatment had an OR of 6.2 for estradiol (95% confidence interval [CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Following combined estrogen-progestin use, the association was considerably weaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with cyclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use). CONCLUSION: The risk of developing endometrial cancer is increased after long-term use of estrogens without progestins and with cyclically added progestins. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.
Case-control studies of lifestyle factors have been inconclusive in the study of endometrial cancer, and prospective data are scarce. Our aim was to examine the associations of physical activity, weight and weight change, fruit, vegetable, and alcohol consumption, socio-economic status, parity and presence of diabetes mellitus with the risk of endometrial cancer in a cohort study. In 1967, 11,659 women in the Swedish Twin Registry, born 1886-1925, answered a 107-item questionnaire, including questions about diet, physical activity and other lifestyle factors. Complete follow-up through 1992 was attained through record linkage to the Swedish Cancer and Death Registers. The relative risks for endometrial cancer were estimated in proportional hazards models that adjusted confidence limits for correlated outcomes. We observed 133 incident cases of endometrial cancer in the cohort. There was no clear pattern of risk over strata of alcohol or fruit and vegetable intake, although the data suggest an increased risk with very low fruit and vegetable intake. Increasing physical activity markedly decreased the risk of endometrial cancer (p for trend < 0.01), independently of weight and parity; the risk in the highest quartile, relative to the sedentary category, was 0.2 (95% CI 0.3-0.8). As expected, higher weight in middle age increased the risk (p for trend < 0.01), as did higher weight in early adulthood. Contrary to previous findings, weight gain did not have an effect independent of weight at enrollment. We did not find a genetic component to endometrial cancer. Our results confirm that environmental factors are the most important, especially physical activity, parity, and weight in young and middle age.
BACKGROUND: Urogenital symptoms are common among postmenopausal women. Such symptoms may be alleviated by low-potency oestrogen formulations administered orally or vaginally. Although low-potency oestrogen formulations are assumed to have few, if any, adverse effects on the endometrium, risk of endometrial neoplasia has not been quantified. METHODS: In a nationwide population-based case-control study in Sweden of endometrial cancer among postmenopausal women, we obtained detailed information on hormone replacement from 789 cases of endometrial cancer and 3368 population controls. In a histopathological review, 80 cases were reclassified as having endometrial atypical hyperplasia. Odds ratios and 95% CI were calculated with unconditional logistic regression. FINDINGS: After multivariate adjustment, oral use of oestriol 1-2 mg daily increased the relative risk of endometrial cancer and endometrial atypical hyperplasia: the odds ratios for at least 5 years of use compared with never use were 3.0 (95% CI 2.0-4.4) and 8.3 (4.0-17.4), respectively. The association was stronger for well-differentiated cancers and those with limited invasion. The excess relative risk was lost rapidly after cessation of treatment. Only weak associations were observed between vaginal application of low-potency oestrogen formulations and relative risk of endometrial neoplasia. INTERPRETATION: Oral, but not vaginal, treatment with low-potency oestrogen formulations increases the relative risk of endometrial neoplasia. Thus close surveillance of patients is needed, and addition of a progestagen should be considered.
While use of hormone-replacement therapy (HRT) effectively alleviates menopausal symptoms and prevents osteoporosis and possibly cardiovascular disease, there is concern of a detrimental impact on breast-cancer risk. There is a particular lack of data regarding the effect of long-term use of oestrogen-progestin combinations on breast-cancer risk. We conducted a large epidemiological study in Sweden, where combined oestrogen-progestin treatment has been predominant, to examine the influence of different regimens of menopausal hormone therapy on breast-cancer risk. In this population-based case-control study, 3,345 women aged 50 to 74 years with invasive breast cancer (84% of all eligible) and 3,454 controls of similar age (82% of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on use of hormone replacement and on potential confounding factors. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multiple logistic regression. There was a trend of increasing breast-cancer risk with duration of oestrogen/oestrogen-progestin use (OR for women treated at least 10 years, 2.43; 95% CI, 1.79-3.30, as compared to never-users), with statistically significant estimates only for women with BMI<27 kg/m2. Excess risks were observed to current use and use that ceased more than 10 years ago (OR for women treated at least 5 years, OR was 2.68, 95% CI, 2.09-3.42, and OR 2.57, 95% CI, 1.28-5.15, as compared with never-users, respectively). A positive association which was noted for use of oestrogen combined with testosterone-derived progestins appeared especially pronounced with continuously combined regimens. Long-term use of replacement oestrogens with or without progestins may substantially increase the incidence of post-menopausal breast cancer, particularly among non-obese women.
Epidemiologic studies have suggested an increased risk for ovarian cancer associated with the use of talcum powder in genital hygiene, but the biologic credibility of the association has been questioned. We conducted a population-based case-control study in eastern Massachusetts and New Hampshire involving 563 women with newly diagnosed epithelial ovarian cancer and 523 control women selected either by random digit dialing or through lists of residents. Use of body powders was assessed through personal interview and the exposure odds ratio (OR) for the use of talc in genital hygiene was calculated. Cases were more likely than controls (45% vs. 36%) to have used talc as a body powder in some manner, and the excess was confined to patients who used talc on the perineum directly or as a dusting powder to underwear or sanitary napkins. Relative to women who never used body powder or used it only in non-genital areas, the OR (and 95% confidence interval) associated with genital exposure to talc was 1.60 (1.18 and 2. 15) after adjustment for age, study location, parity, oral contraceptive use, body mass index and family history of breast or ovarian cancer. Exposure prior to rather than after a first livebirth appeared to be more harmful, and the association was most apparent for women with invasive serous cancers and least apparent for those with mucinous tumors. We conclude that there is a significant association between the use of talc in genital hygiene and risk of epithelial ovarian cancer that, when viewed in perspective of published data on this association, warrants more formal public health warnings.
BACKGROUND: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. METHOD: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. FINDINGS: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. INTERPRETATION: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.
It is unclear whether age at menarche is causally involved in breast-cancer aetiology, or serves a correlate of other early-life exposures. Other aspects of reproductive life, including cycle length and regularity, climacteric symptoms, reproductive history and oral contraceptive use, are also incompletely investigated. We examined these issues in a population-based case-control study, including 3,016 women aged 50 to 74 years with invasive breast cancer, and 3,263 controls of similar age. Mailed questionnaires and telephone interviews were used to collect information on menstrual and reproductive characteristics as well as use of oral contraceptives. We found a statistically significant negative association between increasing age at menarche and breast-cancer risk in women born before 1925 but not after. Length of the menstrual cycle at age 30 seemed to be adversely related to breast-cancer risk, with OR for women with cycle lengths < 24 days and > 30 days being 0.76 and 1.18, as compared with women with a cycle length of 28 days. There was a strong trend of decreasing breast-cancer risk with increasing parity (OR per borne child 0.85, 95% CI 0.80-0.90). Lactation, menopausal symptoms or past use of oral contraceptives did not appear associated with breast-cancer risk. Our findings provide some evidence of a role of environmental correlates of early menarche in breast-cancer aetiology, and underline the importance of childbirth, especially early in life, in the prevention of breast cancer. Our data are not readily compatible with an important influence of former oral contraceptive use on post-menopausal breast-cancer risk.
BACKGROUND AND METHODS: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.
The two types of hip fracture--cervical and trochanteric femoral fractures--are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case-control study in Swedish women, 50-81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15-1.32) compared with an OR of 1.06 (95% CI 0.97-1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0. 91-0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12-1.95) for trochanteric fractures and 1.22 (95% CI 0.98-1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0. 55 (95% CI 0.33-0.92) compared with 1.00 (95% CI 0.71-1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions.
Using data from the 5% U.S. Medicare sample, we estimated the actuarial (life table) risk that a person aged 65 will fracture the upper or lower limbs or the pelvis, by age 75, 80, 85, and 90, taking into account the chance of dying in the interval. The actuarial risk of a 65-year old white woman sustaining a fracture by age 90 is 16% for the hip, 9% for distal forearm, 5% for proximal humerus, and 4% for ankle. Black women and white men have substantially lower risks, and the risks for black men are very low. Although hip fractures pose the single greatest risk, the risk of all other fractures combined is greater. White women have particularly high risks for all fractures, because of their longevity as well as their high fracture rates. It is important to adjust for the probability of dying when estimating risks in an elderly population.
OBJECTIVE: Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change. METHODS: The data derive from a population-based case-control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n = 2015) were identified through state tumor registries and controls (n = 2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women. RESULTS: We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P = 0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger). CONCLUSION: Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women.
OBJECTIVES: To estimate the magnitude and persistence of the protective effect of use of combined oral contraceptives (COCs) and endometrial cancer risk. METHODS: We performed a nation-wide, population-based case-control study among postmenopausal women aged 50-74 years in Sweden, which included 709 subjects with incident, histopathologically verified endometrial cancer, and 3,368 controls with an intact uterus. We used unconditional logistic regression to calculate odds ratios as estimates of relative risks. RESULTS: Use of any sort of oral contraceptive decreased risk for endometrial cancer by 30%, while progestin-only pills reduced risk more markedly. For COCs the reduction in risk was noticeable following 3 or more years of use (OR 0.5, 95% CI 0.3-0.7), and increased with duration of intake, reaching 80% lower risk after 10 years of use. The protective effect of COC use was similar for all degrees of tumor differentiation and invasiveness, and remained for at least 20 years after cessation of use. Subsequent use of hormone replacement did not modify these protective effects. CONCLUSIONS: We conclude that COC use confers a long-lasting protection against endometrial cancer risk which is particularly marked for long-term users.
Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.
OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. SETTING: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.
BACKGROUND: There is considerable interest in the possibility of an infectious etiology for human breast cancer. Although studies have shown that certain strains of mice transmit mammary tumor virus via breast milk, few epidemiologic studies have addressed this topic in humans. METHODS: We evaluated the relationship between having been breast-fed as an infant and breast cancer risk among 8299 women who participated in a population-based, case-control study of breast cancer in women aged 50 years or more. Case women were identified through cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin); control women were identified through statewide driver's license lists (age <65 years) or Medicare lists (ages 65-79 years). Information on epidemiologic risk factors was obtained through telephone interview. We used multiple logistic regression to assess having been breast-fed and maternal history of breast cancer in relation to breast cancer occurrence both in premenopausal women (205 case women; 220 control women) and in postmenopausal women (3803 case women; 4071 control women). RESULTS: We found no evidence that having been breast-fed increased breast cancer risk in either premenopausal women (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.41-1.04) or postmenopausal women (OR = 0.95; 95% CI = 0.85-1.07). In addition, breast cancer risk was not increased by having been breast-fed by a mother who later developed breast cancer. CONCLUSION: Our results do not support the hypothesis that a transmissible agent in breast milk increases breast cancer risk. Because premenopausal women were not well represented in our study population, our findings with regard to this group may not be generalizable and should be viewed with caution.
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