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Reproductive factors and the risk of brain tumors: a population-based study in Sweden.

Possible associations between childbearing and the risk of brain cancer were explored in a case-control study "nested" within a large nationwide cohort defined by the Swedish Fertility Registry. Among women born between 1925-1975, 1,088 patients with meningiomas and 1,657 patients with gliomas were identified in the Swedish Cancer Registry. For every woman diagnosed with brain tumor, 5 age-matched controls were selected among those in the Fertility Registry. Relative risks were estimated by odds ratios from conditional logistic regression. Ever-parous women were at a reduced risk of glioma compared to nulliparous women, while parity was unrelated to meningioma risk. Age at first birth was unrelated to both meningioma and glioma risk. The gradient in risk between ever-parous and nulliparous women for gliomas, but not meningiomas, is difficult to explain biologically. A possible explanation is that pregnancy-induced alterations in androgen levels reduce the risk of glioma in parous women. Alternatively, childlessness may represent a marker of an occult glioma, negatively affecting fecundity. Overall, our present results do not support the notion that hormonal changes, or other physiological changes induced by childbearing, play an important role in the development of brain tumors.

Adult↗

Anthropometric indices in relation to mammographic patterns among peri-menopausal women.

The relationship between body height, weight and body mass index and mammographic patterns was examined among 3,208 Norwegian women, aged 40-56 years, participating in the Third Tromsø study. Standardized measurements of height and weight were recorded. Epidemiologic data were obtained through questionnaires. Mammograms were categorized into 5 groups based on anatomic-mammographic correlations. For analysis, patterns I-III were combined into a low-risk group and patterns IV and V into a high-risk group. Odd ratios (ORs), adjusted for menopausal status, age, parity, age at first birth, age at menarche and anthropometric measures, with 95% confidence intervals (CIs), were calculated. Body height was associated positively with high-risk patterns, while weight and body mass index were associated inversely with high-risk patterns. Women in the highest tertile of height were twice as likely (OR = 2.0, 95% CI 1.6-2.6) to have high-risk patterns compared with those in the lowest tertile, and women in the highest tertile of weight were 70% less likely (OR = 0.3, 95% CI 0.2-0.4) to have high-risk patterns compared with those in the lowest tertile. Associations with body mass index were similar to those with weight. All associations were present when stratified by menopausal status. Among post-menopausal women, the inverse associations between body weight and body mass index and high-risk patterns decreased with increasing number of years since menopause. Our results indicate that body height and weight are independently associated with the mammographic pattern among peri-menopausal women. We suggest that body height and weight are related to mammographic patterns through different mechanisms.

Adult↗

Variation in female breast cancer risk by occupation.

Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age of first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only "administrative support occupations" had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% CI 1.06-1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated.

Administrative Personnel↗

Inclusion of risk factor covariates in a segregation analysis of a population-based sample of 426 breast cancer families.

Although many segregation analyses of breast cancer have been published, few have included risk factor covariates. Maximum likelihood segregation analyses examining age-at-onset (model 1) and susceptibility (model 2) models of breast cancer were performed on 426 four-generation families originally ascertained between 1944 and 1952 through a breast cancer proband. Cancer status and risk factor data were collected through interviews of participants or surrogates. When segregation analyses were performed on 10,791 women, without estimation of any covariates, all hypotheses under both models were rejected. Model 1, which required estimation of fewer parameters than model 2, provided a better fit to the data according to Akaike's Information Criterion. Further segregation analyses were performed under model 1 on a subset of women with complete data on education, age at first birth (nulliparous women included), and alcohol use, covariates that were found to significantly (P<0.05) improve the fit over the addition of exam age alone in logistic regression models. All three covariates improved the fit of the models, as did year of birth, but at all stages of model building, all of the hypotheses were still rejected. After the allele frequency was fixed at 0.0033, a subset of families appeared to fit a dominant model. Using this model, risk estimates were calculated based on inferred genotype, age, and covariate values. The penetrance was estimated to be 0.15, much lower than previous estimates based on families ascertained through breast cancer probands with early onset. Moreover, the estimates of penetrance were not greatly influenced by incorporation of the measured risk factors.

Adult↗

What should the physician ask?

The physician who deals with the general public rather than with high risk groups has a considerable disadvantage to overcome. This is because the effectiveness or impact of a control program is directly related to the prevalence of the condition sought in the population at hand. Thus, the physician must develop a set of "verbal screens" which will permit him to select the sub-segments of his general population which should be screened conventionally. These verbal screens may be of two types: 1) a simple inquiry as to whether a generally accepted screening test has been applied within the last year or two, and 2) an inquiry as to whether any risk factors of the more common cancers are present. For cancer of the cervix, women who have first intercourse at an early age or who are of the lower social strata should be identified for screening. For breast cancer, women who are nulliparous, have first birth at a late age, or a family history of breast cancer should be identified.

Age Factors↗

The combined effect of breast cancer risk factors.

An extension of the logistic model (Cox, 1970) is applied to the prospective study of breast cancer in Guernsey (Bulbrook and Hayward, 1967). Four important risk factors, age at menarche, family history, age at first birth and etiocholanolone excretion, are identified and shown to have additive effects on a logistic scale for the probability of developing breast cancer. The feasibility of screening a high risk group of women is considered and shown unlikely to be of practical value.

Adult↗

Reproductive history and risk of breast cancer: a case-control study in an unselected Swedish population.

Variables in reproductive histories were studied in 179 consecutively detected, unselected breast cancer patients and age-matched controls selected from a computerized population register. The comparison between patients and controls showed no significant difference in age at meanarche, age at first birth, age at menopause or number of children. A subdivision into pre- and post-menopausal women yielded no further information. These results are at variance with most earlier reports, possible because the controls here were selected from the whole female population instead of hospitalized patients. Our data do not support the view that it is possible to define groups at high risk for breast cancer on the basis of productive histories.

Adult↗

The epidemiology of breast cancer in 785 United States Caucasian women.

A retrospective case-control hospital study of 785 Caucasian breast cancer patients and 2,231 age-stratified controls was conducted in New York City from 1969-1975. Patients were grouped by pre- peri- and postmenopausal status at diagnosis for the analysis to make a distinctive separation for variables showing a pre- and postmenopausal differential. Demographic characteristics were similar for cases and controls. Previously recorded hormone-related risk variables for this disease were largely confirmed for pre- and perimenopausal women, i.e., late age at first birth (greater than 25), premenstrual symptoms of breast swelling and premenopausal chills and flushes. Mother's history of breast cancer was also found to be a risk variable. Nulliparity was a risk factor only perimenopausally. No risk was foun for absolute height, weight or for obesity (Quetelet Index), prior breast diseases or previous usage of exogenous hormones of any type and no "protective" effect was found for multiparous women and for nursing. Perimenopausally diagnosed patients (menopause to 10 years after) were similar to premenopausally diagnosed women on most risk factors. Risk variables determined by this and other case-control studies cannot account for the magnitude of differences in the international incidence of breast cancer.

Adult↗

Clinical implications of risk factors for breast cancer.

Little is known about the actual causes of breast cancer, but a great deal is known about risk factors: characteristics of individual patients that increase their chances of developing breast cancer above the level of risk in the general population. The factors may be classed generally as genetic (familial history), hormonal (age at menarche and at menopause, parity, age at first birth, etc.), nutritional (possibly including social, economic, and ethnic factors), morphologic (proliferative breast disease, including cancer predictive of later risk), and breast irradiation. Because current understanding of how these risk factors relate to breast cancer causation is minimal (except for irradiation), there are few practical measures for primary prevention. However, there can and should be major use of current knowledge in arranging secondary prevention through screening and possibly even prophylactic mastectomy. The author's concern was that, at the time the National Conference on Breast Cancer was arranged, there was little consideration of breast cancer risk in the woman who lacked risk factors. Since that time, other authors have published a strong statement to the effect that breast cancer rates still are substantial and important in these women. In the current report, the author illustrates the same point for other "low-risk" groups to support the argument that by current knowledge, no adult American woman is at such low risk for breast cancer that she can safely be excluded from the educational and screening programs appropriate for her age.

Adolescent↗

Expression of GCDFP-15 in breast carcinomas. Relationship to pathologic and clinical factors.

A retrospective immunoperoxidase staining study for a glycoprotein isolated from human breast gross cystic disease fluid (GCDFP-15) in 562 primary breast carcinomas in 539 patients was conducted to correlate its immunohistochemistry with pathologic and clinical factors. Overall, 55% of the carcinomas studied stained positively for GCDFP-15. In certain histologic subtypes, the percentage of carcinomas that stained positively was greater: those subtypes with apocrine histologic features (75%), intraductal carcinoma (70%), and infiltrating lobular carcinoma with signet-ring cell differentiation (90%). In contrast, only 5% of medullary carcinomas exhibited positive staining. Only 23% of breast carcinomas without apocrine features stained positively for GCDFP-15. Carcinomas that stained positively were more likely to have involved axillary lymph nodes (P less than 0.054). The staining was independent of nuclear grade, mitotic index, tumor size, and estrogen receptor status. Positive staining was related to a history of gross cystic disease but not to age, parity, menopausal status, or age at first birth. A positive stain was not related to risk of recurrence or survival.

Apolipoproteins↗

Estrogen and progesterone receptors in breast cancer patients. Epidemiologic characteristics and survival differences.

Risk factors commonly associated with breast cancer were studied in relation to: (1) tumor estrogen receptor (ER) or progesterone receptor (PR) status and (2) the presence of tumor hormone receptors in relation to subsequent survival. For 171 Israeli women diagnosed with breast cancer in 1976 to 1979, tumor hormone receptor status (positive if greater than 20 fmol receptors/mg protein; negative if less than or equal to 20 fmol/mg) and survival as of April 1984 were ascertained. There were 77 ER- versus 94 ER+ and (for 134 PR analyses) 69 PR- versus 65 PR+. Although ER status and PR status were found to be highly positively related, the epidemiologic features of women with an ER+ tumor were different from those with a PR+ tumor. Age tended to be associated positively with both ER+ and PR+. Being postmenopausal, older at menopause or at first birth, nulliparous, having more years of schooling, and a higher body mass index for older women or a lower body mass index for younger women were correlated positively with ER and negatively with PR. Among women with Stage III or IV tumors at diagnosis significant differences existed: restricted mean survival for follow-up time was 47.2 months for ER-, 73.8 months for ER+, 45.8 months for PR-, and 61.9 months for PR+. The combined hormone effects on survival at Stages III to IV showed a similar trend: restricted mean survival of 38.4 months for ER-PR-, intermediate survival with one positive hormone receptor status, and 74.6 months for ER+PR+.

Adult↗

Non-parametric maximum likelihood estimators for disease mapping.

A Non-Parametric Maximum Likelihood approach to the estimation of relative risks in the context of disease mapping is discussed and a NPML approximation to conditional autoregressive models is proposed. NPML estimates have been compared to other proposed solutions (Maximum Likelihood via Monte Carlo Scoring, Hierarchical Bayesian models) using real examples. Overall, the NPML autoregressive estimates (with weighted term) were closer to the Bayesian estimates. The exchangeable NPML model ranked immediately after, even if it implied a greater shrinkage, while the truncated auto-Poisson showed inadequate for disease mapping. The coefficients of the autoregressive term for the different mixtures have clear interpretations: in the breast cancer example, the larger cities in the region showed high rates and very low correlation with the neighbouring areas, while the less populated rural areas with low rates were strongly positively correlated each other. This pattern is expected since breast cancer is strongly correlated with parity and age at first birth, and the female population of the rural areas experienced a decline in fertility much later than those living in the larger cities. The leukemia example highlighted the failure of the Poisson-Gamma model and other general overdispersion tests to detect high risk areas under specific conditions. The NPML approach in Aitkin is very general, simple and flexible. However the user should be warned against the possibility of local maxima and the difficulty in detecting the optimal number of components. Special software (such as CAMAN or DismapWin) had been developed and should be recommended mainly to not experienced users.

Algorithms↗

Fifty years of chimpanzee demography at Taronga Park Zoo.

There has been a captive Pan troglodytes colony at Taronga Park Zoo in Sydney, Australia, since the mid-1930s. Demographic data on these animals were first analyzed in 1986; however, further information collected for 15 years since then is now available. The reproductive histories of 33 females in the colony have been recorded, and these data form the largest collection of captive chimpanzee data from a setting that has involved natural breeding conditions since the mid-1960s. These data were analyzed in conjunction with data from wild populations to establish the degree of variability present within chimpanzee reproductive parameters, and to identify which distinctive life history characteristics persist in well-provisioned, natural-fertility populations. The age at first birth for the chimpanzee females is 9.8 yr on average (n=16), which is 1-4.8 yr earlier than the average for wild populations. In line with this accelerated reproduction, birth intervals are also significantly shorter than those in noncaptive chimpanzee populations. The median birth interval for all surviving infants (based on a Kaplan-Meier survival analysis) is 49 months (n=43) compared to 62+ months for wild groups. At the same time, infant mortality remains high. The data confirm distinctive features of the life history of common chimpanzees, including later maturation, long birth intervals, a relatively invariant fertility schedule, and high juvenile mortality. However, aspects of both fertility and mortality are significantly related to social circumstances, indicating that in common chimpanzees, as in humans, life history characters may represent ecological and social adaptations rather than species-fixed characteristics.

Age Factors↗

Biological and behavioral determinants of fertility in Tierra del Fuego.

The reproductive history of 182 women in postreproductive life or near menopause from the Chilean part of Tierra del Fuego was traced back by means of familial interviews. These postmenopausal women represent the population since almost the beginning of the settlement, and their reproductive years were spent on the island. Path analysis was applied to analyze fertility determinants of these women and to propose a complex model of interconnections among factors. The reproductive history of these women is characterized by a long fertile span, a short childbearing period, and low fertility. Age at menarche is relatively late, and the age of the women at first birth is mainly determined by their late age at marriage. The use of contraception is related to both spacing and stopping behaviors. The late age of women at marriage, the rhythm of conception, and practices of contraception are proposed as the main determinants of fertility in Tierra del Fuego.

Age Factors↗

Physical activity and breast cancer risk among female physical education and language teachers: a 34-year follow-up.

The cohort consisted of 1,489 Finnish female physical education and 8,560 language teachers born after 1920 and alive in 1967. The 2 study populations were similar in social class and way of living and clearly discordant in physical activity both during their university studies and later in life. The incidence of breast cancer among these teachers up to the year 2000 was assessed through a record linkage with the Finnish Cancer Registry. The number of breast cancer cases among physical education teachers was 61 in 32,862 person-years and among language teachers was 404 in 177,188 person-years. In Poisson-regression analysis, the incidence rate ratio--adjusted for age, calendar time, number of children and age at first birth--for physical education vs. language teachers was overall 0.83 (95% confidence interval 0.63-1.09). This relative rate was 0.79 (0.46-1.36) in ages <50 years and 0.86 (0.62-1.18) in ages > or =50 years. Our study is concordant with the hypothesis that life-long physical activity may reduce the risk of breast cancer.

Adult↗

Education and risk of breast cancer in the Norwegian-Swedish women's lifestyle and health cohort study.

A positive relationship between level of education and female breast cancer risk is well supported by scientific evidence, but few previous studies could adjust for all relevant potential confounding factors. The authors' purpose was to examine how risk for breast cancer varies with level of education and to identify factors that explain this variation, using data from a prospective cohort study including 102860 women from Norway and Sweden who responded to an extensive questionnaire in 1991/1992; 1090 incident primary invasive breast cancer cases were revealed during follow-up, which ended in December 1999. The Cox Proportional Hazards Model was used to calculate relative risks (RR) with 95% confidence intervals (CI). Women with more than 16 years of education had a 36% increased risk compared to the lowest educated (7-9 years) (Age adjusted RR=1.36, 95% CI: 1.10, 1.68). This relationship was slightly stronger among postmenopausal (RR 1.51) than among premenopausal (RR 1.25) women. In both groups, however, the relative risk estimates turned close to unity by adjustment for parity, age at first birth, body mass index (BMI), height, age at menarche, menopausal status, use of oral contraceptives and consumption of alcohol. The overall multivariate relative risk among the highest educated women was 1.04 (95% CI 0.82-1.32). The results of our study suggest a clear positive gradient in risk for breast cancer by level of education, which can be fully explained by established breast cancer risk factors.

Adult↗

Maternal breast cancer risk after the death of a child.

The possible association between a severe traumatic life event (death of a child) and breast cancer risk was examined in a case-control study nested within a nation-wide cohort in Sweden. Our study population included 27,571 women with breast cancer and 141,798 control women born between 1925-1976. After adjustment for age, parity, age at first birth and education, the overall risk estimate for breast cancer among all women that had experienced the death of a child was 1.05 (95% confidence interval [CI] = 0.96-1.15). Among uniparous women the corresponding odds ratio (OR) was 1.27 (95% CI = 0.98-1.64). When stratifying for child's age at death a significant risk increase was detected among women that had lost their only child when the child was between 1-4 years of age (OR = 2.65; 95% CI = 1.06-6.60). These findings do not support an overall increase in breast cancer risk after the death of a child, a severe traumatic life event. Based on a small number of subjects, our finding of an increased risk in a subgroup of uniparous women losing their only child could be due to chance.

Adolescent↗

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers.

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

Adolescent↗