Alcoholic beverage consumption and the risk of endometrial cancer. Cancer and Steroid Hormone Study Group

Previous studies have suggested that alcoholic beverage consumption may lead to a decrease in a woman's oestrogen levels. It is possible that any such alcohol-associated decrease could lead to a decrease in endometrial cancer risk. To study the association between alcohol consumption and endometrial cancer, we examined data from the Cancer and Steroid Hormone Study, a multi-centre, population based, case-control study. A total of 351 women with primary epithelial endometrial cancer and 2247 women selected from the same geographical areas as the cases were interviewed for the study. As part of the interview, the participants provided information regarding their alcohol consumption during the preceding five years. Analysis of these data revealed that women who were non-drinkers had a risk of endometrial cancer of 1.83 relative to the risk of women who had consumed an average of 150 grams or more of alcohol per week (95% Cl, 1.11, 3.01). Women who drank, but who consumed less than 150 grams of alcohol per week, were at an intermediate risk. The increased risk associated with abstinence from alcohol consumption was particularly great in overweight women and was virtually absent in lean women. These results argue that alcohol ingestion may reduce a woman's risk of endometrial cancer, particularly if she is overweight.     

Age at first full-term pregnancy, lactation and parity and risk of breast cancer: A case-control study in Spain

A case-control study was carried out in Spain to assess associations between parity, lactation and age at first full-term pregnancy and breast cancer. From November 1989 to February 1992, 184 incident breast cancer histologically confirmed cases were interviewed and matched by age and residence to 184 hospitalized patients and 184 community controls selected by random digit dialing. Multiple logistic regression was used to assess the independent influence of each factor on the risk of breast cancer in relation to other factors included in the model. Age at first full-term pregnancy was associated with breast cancer risk with an estimated odds ratio of 3.5 (95% CI 1.41–9.83) for women with their first birth after 30 years in comparison with those whose first birth was before age 21. Breast cancer risk decreased with increasing number of full-term pregnancies, OR 0.3 (95% CI 0.16–0.78) for women who had had more than 3 full-term pregnancies in comparison with nulliparous women. Among parous women, the estimated OR for women with more than 3 children was 0.4 (95% CI 0.13–0.81) after allowance for age at first childbirth and lactation. The estimated OR was 2.6 (95% CI 1.4–4.7) for women with a positive history of breast cancer in first-degree relatives. Breast cancer was not associated with total duration of lactation. The study indicates that parity is an independent risk factor associated to breast cancer and that the women with a late age at first full-term pregnancy constitute a high-risk group.     

Children, age at first birth, and colorectal cancer risk. Data from the Melbourne Colorectal Cancer Study

During 1980 and 1981, data were obtained on the number of children and age at birth of the first child in 675 cases of colorectal cancer and in 720 age-sex frequency-matched controls as part of a large epidemiologic study of colorectal cancer conducted in Melbourne, Australia. For colorectal cancer, the relative risk (RR) for those with one or more children compared with those with no children was statistically significantly lower than one (RR = 0.61, 95% confidence interval (CI): 0.45-0.81, p less than 0.001), and with simultaneous adjustment for number of children, there was an increasing risk with increasing age at birth of first child (RR = 1.03, with each increasing year of age at birth of first child, 95% CI: 1.00-1.05, p = 0.02). The relation between both the number of children and the age at birth of the first child and colorectal cancer risk was not statistically significantly different for males and females. The risk of colorectal cancer with respect to number of children and age at birth of the first child was unaffected by the potential confounding factors of age, occupation, previous diet, oral contraceptive use in females, and a family history of colorectal cancer. Since the protection against colorectal cancer associated with having children and with earlier age at birth of the first child was found to be similar for both males and females in the Melbourne study, a life-style factor, as yet unidentified, rather than a female hormonal factor, is postulated as the mediator of these effects.     

Research on infertility: definition makes a difference. The Cancer and Steroid Hormone Study Group

Although different definitions of infertility are used, research findings based on various definitions have not been systematically compared. To contrast the impact of five definitions of infertility on research findings, the authors analyzed data from the control group (randomly selected US women aged 20-54 years) of the Cancer and Steroid Hormone Study (1980-1983). For all definitions, an absence of recognized conception was the outcome of interest. Specifically, the authors examined the effect of various definitions of infertility on demographic characteristics of women classified as infertile, prevalence of a history of infertility, age at infertility classification, and cumulative incidence of conception after infertility classification. Results indicated that women classified as infertile by definitions based on unprotected intercourse for 12 months and unprotected intercourse for 24 months were more likely to be black, less educated, and classified as infertile at younger or older ages that women classified by alternative definitions. The prevalence of a history of infertility ranged from 6.1% (physician diagnosis) to 32.6% (unprotected intercourse for 12 months). For the definitions based on unprotected intercourse for 12/24 months and for physician diagnosis, the cumulative incidence of conception by greater than 120 months after infertility classification was 86.3%, 76.7%, and 75.4%, respectively. The authors conclude that the definition of infertility has an impact on research findings related to which and how many women are classified as infertile, the age at infertility classification, and the probability of future conception.     

The relationship between body mass and breast cancer among women enrolled in the Cancer and Steroid Hormone Study

We examined the relationship between body mass [weight (kg)/height (m)2] and breast cancer using data from the Cancer and Steroid Hormone Study. The study compared 4323 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4358 women randomly selected from the general population of the same geographic areas. Among naturally menopausal women, risk of breast cancer increased with increasing body mass index (BMI); those severely overweight (BMI greater than or equal to 32.30) had nearly 3-fold higher risk of breast cancer compared with women in the leanest category (BMI less than 20.00). This positive association appeared stronger with increasing years since menopause and in women who had ever used estrogen replacement therapy. A positive association between body mass and breast cancer risk also was observed among premenopausal women; however, risk estimates were substantially lower. Substantial weight gain from adolescence to adulthood was a more important risk factor than lifelong obesity. Prevalence of obesity increases with age; our results suggest that interventions that prevent this trend could have an important effect on breast cancer risk, especially during the menopausal years.     

Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancer

The authors reevaluated 10,542 consecutive breast biopsies of women who presented at three Nashville hospitals. Median follow-up was 17 years for 3,398 women (84.4% of patients originally selected for follow-up). Breast cancer relative risks associated with no proliferative disease, proliferative disease without atypia, and atypical hyperplasia were 0.80, 1.4, and 4.0 times that for women from the Cancer in Connecticut data base, respectively (adjusted for age at biopsy, year of biopsy, and length of follow-up). Nulliparous women were at increased risk of breast cancer (relative risk = 1.6; 95% confidence interval (CI) = 1.1-2.2). Women who gave birth to their first child before age 21 years had a relative risk of 0.80, with higher cancer risks associated with later age at first birth. The effect of age at first birth on cancer risk followed a similar pattern within the no proliferative disease, proliferative disease without atypia, and atypical hyperplasia groups. Nulliparous women with atypical hyperplasia had a relative risk of 4.9 (95% CI = 2.7-8.9), while women with no proliferative disease who gave birth before age 21 years had a relative risk of 0.50 (95% CI = 0.19-1.3). Nulliparous women with a family history of breast cancer had a relative risk of 2.7 (95% CI = 1.4-5.2). Women with a family history who first gave birth by age 20, between ages 21 and 29, and after age 30 years had relative risks of 0.53, 2.1, and 4.0, respectively (95% CI = 0.08-3.8, 1.1-3.9, and 1.8-9.6, respectively). Breast size had no effect on cancer risk in women without proliferative disease. However, in women with proliferative disease, small, medium, and large breasts were associated with relative risks of 1.2, 1.4, and 2.1, respectively.     

Alcohol dose, frequency and age at first exposure in relation to the risk of breast cancer

Habitual alcohol consumption, in terms of dose and frequency, average daily intake, as well as drinking alcohol at age 25 were compared between 120 incident breast cancer cases and 164 population controls in The Netherlands. Dietary and lifestyle factors, past and present alcohol consumption were established in 1985-1987 in home interviews. In premenopausal women a protective effect of low alcohol consumption (1-4 g/day) as compared to non-drinkers was suggested. The multivariate adjusted odds ratio (OR) comparing women drinking greater than or equal to 30 g with women drinking 1 to 4 g alcohol daily was 8.5 (95% confidence interval: (Cl) = 1.1-65.1). The OR for a dose of alcohol of greater than or equal to 15 g versus 1-14 g was 4.0 (Cl = 1.0-15.6) and for drinking more versus less than three times a week the OR was 2.8 (Cl = 0.8-9.8). In post-menopausal women no association was observed between recent drinking habits and breast cancer risk. In these women, however, the adjusted OR for drinking alcohol before the age of 25 was 2.4 (Cl = 1.0-5.6). Although causal inference is hampered by the cultural aspects of drinking habits, the results suggest that moderate drinking does not increase risk. Drinking more than 30 g daily or a high dose may enhance risk in premenopausal women. Furthermore, an early start to drinking alcohol may increase the relative risk for breast cancer even beyond menopause.     

A prospective study of age at menarche, parity, age at first birth, and coronary heart disease in women

Reproductive events in women are associated with alterations in blood lipids and blood pressure and may therefore influence determinants of coronary heart disease. To investigate the risk of coronary heart disease in relation to age at menarche, parity, and age at first birth, the authors evaluated prospectively the experience of 119,963 US women aged 30-55 years who were free from coronary heart disease in 1976 and were followed through 1982. During 700,809 person-years of observation, 308 incident cases of nonfatal myocardial infarction or fatal coronary heart disease occurred. Younger age at menarche was weakly associated with coronary heart disease (age-adjusted rate ratio of 1.3 for menarche before age 11 years compared with menarche at age 13 years; chi, Mantel extension test for trend = -1.1, p = 0.2). Nulliparous women experienced only a slightly higher rate of coronary heart disease than parous women (rate ratio = 1.2, 95 per cent confidence interval 0.8-1.8). Among parous women, there was no alteration in risk with increasing number of births. Likewise, there was no significant association between age at first birth and coronary heart disease (chi, Mantel extension test for trend = -0.4, p = 0.4). Established risk factors for coronary heart disease nevertheless showed expected relations. These findings show no important association between reproductive experiences and risk of coronary heart disease.     

Maternal age at birth and risk of breast cancer in daughters

Data from a large case-control study of breast cancer were examined to test the hypothesis that maternal age at the birth of female offspring is related to the incidence of breast cancer in daughters. Participants were between the ages of 20 and 54 at the time of the study. Based on results for 2,492 parous women who were newly diagnosed with breast cancer and 2,687 parous controls from the general population, a 15-year increase in maternal age was found to be associated with a 29% increase in the risk of breast cancer in daughters. Adjustment for the daughter's age, her own reproductive history, and other potential confounding factors yielded an estimate of 25% for this increase in risk (95% CI, 8% to 46%). The corresponding increase among 499 nulliparous cases and 457 nulliparous controls was 7%, which was not statistically significantly different in magnitude from the increase among parous women. These findings provide evidence for perinatal influences on the subsequent incidence of breast cancer during adulthood. Although specific mechanisms cannot be inferred directly, the results are consistent with the hypothesis that mutations in the genes of the human egg or sperm play a role in the etiology of breast cancer in female offspring.     

The associations of parity and maternal age with small-for-gestational-age,preterm, and neonatal and infant mortality: a meta-analysis

Background

Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).

Methods

Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.

Results

Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.

Conclusions

Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.

Funding

Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

     

Smoking before the first pregnancy and the risk of breast cancer: a meta-analysis

The authors conducted a meta-analysis of the association between smoking before a first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco carcinogens, and the risk of breast cancer. A search of the published literature through August 2010 identified 23 papers reporting on associations between smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios and 95% confidence intervals, adjusted for known or suspected breast cancer risk factors, were abstracted from each study. Data were pooled using both fixed- and random-effects models. The fixed-effect summary risk ratio for breast cancer among the women who smoked before their first pregnancy versus women who had never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects estimate was similar. The separate fixed-effect risk ratios for smoking only before the first pregnancy (5 studies) or only after the first pregnancy (16 studies) were both 1.07, providing no evidence that breast tissue is more susceptible to malignant transformation from smoking before the first pregnancy. While these small summary risk ratios may represent causal effects, residual confounding could readily produce estimates of this size in the absence of any causal effect.     

Parental age at child's birth and son's risk of prostate cancer. The Framingham Study

The authors examined the relation of parental age at birth to the risk of prostate cancer among sons with the use of data from the Framingham Study. During 42 years of follow-up (1949-1993), 141 prostate cancer cases occurred in 2,164 men. All but six cases were confirmed by histologic report. The incidence rate of prostate cancer increased from 1.70 per 1,000 person-years among sons in the lowest quartile of paternal age (<27 years), to 2.00, 2.32, and 2.74 among those of each increased paternal age category (27-<32, 32-<38, and > or =38 years), respectively. After adjustment for age and other covariates, men in the second, third, and oldest quartiles of paternal age had 1.2, 1.3, and 1.7 times increased risk of prostate cancer compared with men in the youngest quartile (p for trend = 0.049). Further adjustment for maternal age did not change the relation materially. The association of older paternal age with risk of early-onset prostate cancer (<65 years) appeared stronger than that with late-onset disease (265 years). No increased risk of prostate cancer was observed among subjects in the older maternal age category. The effect of increased paternal age on prostate cancer risk may operate through increased germ cell mutation rate or by mechanisms not yet defined.     

#3 Parity,age at first birth,and risk of invasive cervical cancer: Meta-analyses

PURPOSE: The roles of parity and age at first birth as risk factors for cervical cancer remain unclear, although several studies in different populations have examined this question. We performed meta-analyses to predict relative risk of invasive cervical cancer as functions of parity and of age at first birth by fitting a variety of models.METHODS: We fit models relating the logarithm of relative risk for cervical cancer to parity and to age at first birth. Parity models were based on parity-specific relative risk estimates from 21 studies published between 1985 and 2001. Age at first birth models were based on corresponding data from 11 studies published during the same time period. Some models included covariates indicating whether individual studies adjusted for human papilloma virus (HPV) status, number of sex partners, age at first birth (parity models only), and/or parity (age at first birth models only).RESULTS: Relative risk for cervical cancer was found to increase with parity, at a declining rate (i.e., the greatest increase in risk was between parity 0–1, with consistently smaller increases thereafter). Relative risk for first birth at ages ⩾17 was significantly lower than relative risk for first birth at age 13, but no significant relationship was found between relative risk and age at first birth for first birth at ages ⩾17. Overall, indicators of whether studies adjusted for covariates were unable to explain the large variations among study results.CONCLUSION: Risk of invasive cervical cancer was associated with increasing parity, with the greatest increase in risk with the first birth. Risk was decreased for first birth at age 17 compared to 13; for first birth at ages ⩾17, we were unable to derive a quantitative relationship between age at first birth and relative risk for cervical cancer.     

The meaning of risk to first degree relatives of women with breast cancer

Breast cancer represents a serious health concern for women. It is estimated that hereditary breast cancer accounts for approximately 5-10% of all breast cancer cases and as many as 25% of early-onset cases. We conducted a qualitative study of 26 first degree relatives of women with breast cancer (FDRs) in order to gain a deeper understanding of the effect of risk perception on their screening adherence. The method relied upon semi-structured, in-depth, face-to-face interviews with first degree relatives of women with breast cancer. We characterized FDRs by their response to a single query about their perceived risk. "Risk adopters" (N = 13) were defined as those who expressed a lifetime risk of breast cancer of 50% or more, and "normalizers" (N = 13) were those who indicated a lifetime risk of 49% or less. We conducted content analysis on the responses to the open-ended queries concerning perceived risk for breast cancer, searching for consistent themes among the responses. Surveillance behaviors were high among these FDRs relative to population-based comparisons. The difference between perceived and objective risk for breast cancer was significantly greater among risk adopters than normalizers (p < .0001). Three themes, derived from a content analysis of the FDR's natural language, further distinguish the two groups of women from one another: (1) causal attributions; (2) acceptance of labeling by the physician or other health care provider; and (3) current or remembered surveillance reminders from salient members of the social support network. We suggest different health care provider approaches to FDRs who are normalizers and those who are risk adopters, as well as additional studies of the impact of risk status (as manifest in the FDR's natural language) and surveillance behaviors, over time, among more diverse subgroups.     

Maternal body mass index, duration of exclusive breastfeeding and children's developmental status at the age of 6 years

OBJECTIVE: To investigate whether the duration of exclusive breastfeeding and maternal body mass index (BMI) are associated with children's developmental status at the time of beginning elementary school. DESIGN AND SUBJECTS: The subjects in the sample came from a longitudinal study on infant nutrition in Iceland. Food records were made once a month from birth to the age of 12 months, from which duration of exclusive breastfeeding could be determined. Mothers filled in The Icelandic developmental inventory for evaluation of motor and verbal development close to their children's sixth birthday (n = 85). Maternal self-reported weight and height was recorded. Information on socioeconomic factors was gathered by a questionnaire. RESULTS: Duration of exclusive breastfeeding, in months, was positively related to children's motor component (B = 0.5+/-0.5, P = 0.054) and to the total developmental index (B = 1.0+/-0.5, P = 0.044) at 6 y, adjusting for gender and socioeconomic factors (maternal and paternal education, and family income). Children's learning score was negatively related to maternal BMI (B = -0.5+/-0.2, P=0.047). An inverse association also appeared between maternal BMI and two out of the three developmental composite scores, that is, verbal component and the total developmental index (B = -0.6+/-0.3, P=0.049) and (B = -0.4+/-0.2, P=0.057), respectively. In multiple regression the developmental indexes were most strongly independently associated with maternal BMI (negatively) and infants' birth weight (positively). CONCLUSION: Maternal BMI and duration of breastfeeding were associated with verbal and motor development of 6-y-old children, independent of socioeconomic factors. Birth weight was also an independent determinant for developmental scores.     

Mean arterial pressure, pregnancy induced hypertension, and preeclampsia. Evaluation as independent risk factors and as surrogates for high maternal serum alpha-protein in estimating breast cancer risk

PURPOSE: Data from a nested case-control study were analyzed to examine high mean arterial pressure (MAP), hypertension of pregnancy and preeclampsia as independent predictors, and as surrogate markers for elevated Alpha-fetoprotein (AFP) levels in evaluating breast cancer risk.METHODS: Cases (n = 205) were identified by the California Cancer Registry from a cohort of pregnant women who were part of the Kaiser Health Plan and took part in the Child Health and Development Studies initiated by the University of California, Berkeley, from June 1959 to September 1966. Controls (n = 337) were selected by randomized recruitment from the same cohort probability matched to cases by distribution of birth dates of cases.RESULTS: High MAP was associated with breast cancer risk, and was different across quartiles of age at first full term pregnancy. Odds Ratios across quartiles were 0.24 (95% CI = 0.08-0.71), 0.84 (95% CI = 0.39-1.66), 1.00 (referent), and 2.50 (95% CI = 1.21-5.13). Neither diagnosed preeclampsia nor hypertension of pregnancy showed any association with breast cancer risk. When both high Alpha-fetoprotein and high mean arterial pressure were entered into the same analysis neither changed the odds ratio for the other more than eight percent. Additionally, AFP level was not a linear function of MAP.CONCLUSIONS: Although the pattern of odds ratios across quartiles of age at first full term pregnancy were similar for the two variables it can not be concluded that high MAP is an adequate surrogate for high levels of maternal serum AFP, but rather represents some related process which is in and of itself a risk factor for breast cancer.     

Associations of age at marriage and first pregnancy with maternal nutritional status in Nepal

Background and objectivesWomen’s nutritional status is important for their health and reproductive fitness. In a population where early marriage is common, we investigated how women’s nutritional status is associated with their age at marriage (marking a geographical transfer between households), and at first pregnancy.MethodologyWe used data from a cluster-randomized control trial from lowland Nepal (n = 4071). Outcomes including body mass index (BMI) were measured in early pregnancy and trial endpoint, after delivery. We fitted mixed-effects linear and logistic regression models to estimate associations of age at marriage and age at pregnancy with outcomes, and with odds of chronic energy deficiency (CED, BMI <18.5 kg/m²), at both timepoints.ResultsBMI in early pregnancy averaged 20.9 kg/m², with CED prevalence of 12.5%. In 750 women measured twice, BMI declined 1.2 (95% confidence interval 1.1, 1.3) kg/m² between early pregnancy and endpoint, when CED prevalence was 35.5%. Early pregnancy was associated in dose-response manner with poorer nutritional status. Early marriage was independently associated with poorer nutritional status among those pregnant ≤15 years, but with better nutritional status among those pregnant ≥19 years.Conclusions and implicationsThe primary determinant of nutritional status was age at pregnancy, but this association also varied by marriage age. Our results suggest that natal households may marry their daughters earlier if food insecure, but that their nutritional status can improve in the marital household if pregnancy is delayed. Marriage age therefore determines which household funds adolescent weight gain, with implications for Darwinian fitness of the members of both households.     

Family history of breast cancer, mammographic features of breast tissue, and breast cancer risk.

I reexamined the relations of family history of breast cancer in first-degree relatives, mammographic features of breast tissue, and breast cancer risk, using data from three case-control studies. Subjects included 1,047 cases with newly diagnosed breast cancer and 2,329 controls. Family history of breast cancer showed only a weak relation to mammographic features. In addition, while family history and mammographic features were each related to breast cancer risk, associations of these two factors with risk appeared additive. In contrast to previous reports, these data suggest that, to a large extent, family history and mammographic features have independent effects on breast cancer development.