Maternal smoking during pregnancy and testicular cancer in the sons: A nested case–control study and a meta-analysis

Some large ecological studies have noted a significant association of testicular cancer (TC) with maternal smoking during pregnancy, while several more controlled studies have been negative. It has been difficult to obtain reliable data on exposure because of the long lag time to cancer diagnosis. We performed a case–control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal smoking in the risk of TC in the offspring. After reviewing the literature, we also performed a meta-analysis of published studies. For each index mother of the TC patient, three to nine matched control mothers with a cancer-free son born at the same time as the TC case were identified within each cohort. First trimester sera were retrieved from the 70 index mothers and 519 control mothers and were tested for cotinine level by a novel HPLC–MS–MS method developed. No statistically significant association between maternal cotinine level and risk of TC in the offspring was found (OR 0.68; 95% CI 0.35, 1.34). This is the first study based on individual exposure measurements. Its results agree with our meta-analysis of seven previous epidemiological studies (total number of 2149 cases, 2762 controls) using indirect exposure assessment (OR 1.0; 95% CI 0.88, 1.12).     

Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, p_trend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, p_trend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, p_trend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.     

Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women

Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre‐diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case‐control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76–9.72), p_trend = 0.0008 for estradiol, 3.67 (1.71–7.88), p_trend = 0.0007 for estrone, 2.15 (1.05–4.40), p_trend = 0.04 for androstenedione, 1.74 (0.88–3.46), p_trend = 0.06 for testosterone, 2.90 (1.42–5.90), p_trend = 0.002 for DHEAS and 0.46 (0.20–1.05), p_trend = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis. © 2003 Wiley‐Liss, Inc.     

Does the increase of endogenous steroid hormone levels also affect breast cancer risk in Chinese women? A case–control study in Chongqing,China

Accumulating epidemiological evidence suggests that sex steroid hormones are positively associated with the development of breast cancer. However, most of these studies were conducted among Caucasian women and few have been carried out in China. To determine whether the associations of sex steroid hormone levels with breast cancer risk observed by and large in Caucasian populations are also evident in Chinese women, we conducted a case–control study in Chongqing, China. The study included 367 incident breast cancer patients and 367 healthy controls matched on menstrual status, age and periods of blood collection in the menstrual cycle. Plasma concentrations of estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were determined by electrochemiluminescene immunoassay (ECLIA). Conditional logistic regression analysis was performed to examine their associations with breast cancer risk. From comparisons of upper and lower tertiles, we observed statistically significant positive associations with breast cancer risk for plasma estradiol levels in follicular phase (adjusted odds ratio [OR] = 5.48, 95% confidence interval [CI] = 1.58–18.97), luteal phase (OR = 4.23, CI = 1.65–10.87) and postmenopausal (OR = 2.67, CI = 1.20–5.93); for progesterone levels in luteal phase (OR = 3.11, CI = 1.28–7.56), and for testosterone levels in postmenopausal (OR = 2.83, CI = 1.26–6.35). No significant association was found with DHEAS or SHBG. Our study suggests that high circulating levels of estradiol and testosterone are positively associated with increased breast cancer risk in Chinese women, which are generally consistent with the observations in Caucasian populations. © 2008 Wiley‐Liss, Inc.     

Circulating levels of sex steroid hormones and risk of ovarian cancer

Experimental and epidemiological evidence supports a role for sex steroid hormones in the pathogenesis of ovarian cancer. We investigated the association between ovarian cancer risk and pre‐diagnostic blood concentrations of testosterone, androstenedione, DHEAS, estrone and SHBG. A case–control study nested within 3 cohorts, in New York (USA), Umeå (Sweden) and Milan (Italy), included 132 subjects with primary invasive epithelial ovarian cancer. For each case subject, 2 controls were selected who matched a case on cohort, menopausal status, age and date of recruitment and, if premenopausal, day of the menstrual cycle at blood donation. Only women who did not use exogenous hormones at blood donation were included in the study. Conditional logistic regression was used to relate cancer risk to sex steroid hormone concentrations with adjustment for potential confounders. No clear association was observed between ovarian cancer risk and any of the 5 hormones under study. In the premenopausal group, the risk appeared to increase with increasing blood concentrations of androstenedione (upper vs. lower tertile OR = 2.35; 95% CI = 0.81–6.82.), but the small number of subjects in the sub‐group precluded reaching unambiguous conclusions about such association. Our study does not support previous observations relating elevations in blood levels of the major sex steroid hormones to an increased risk of ovarian cancer, but offers some evidence that elevated circulating androstenedione before menopause may be associated with increased ovarian cancer risk. © 2003 Wiley‐Liss, Inc.     

V89L polymorphism of the 5alpha-reductase Type II gene (SRD5A2), endogenous sex hormones, and prostate cancer risk.

We examined the combined effect of circulating sex hormones and SRD5A2 V89L polymorphism on prostate cancer risk in a case-control study (300 cases and 300 controls) nested within the Carotene and Retinol Efficacy Trial. A moderate increase in risk associated with above-median serum levels of androstenedione and dehydroepiandrosterone sulfate (DHEAS) was present irrespective of V89L genotype. However, in L/L or V/L men, above-median DHEAS levels were associated with an increased risk of aggressive tumors [odds ratios (OR), 3.12; 95% confidence interval (95% CI), 1.28-7.63] but not of nonaggressive ones (OR, 0.56; 95% CI, 0.25-1.25). Above-median serum levels of free estradiol were associated with a lower risk, especially for aggressive cancer. The association with aggressive disease was more pronounced in men with a V/V genotype (OR, 0.34; 95% CI, 0.14-0.81), than in men with an L/L or V/L genotype (OR, 0.77; 95% CI, 0.37-1.60). Above-median levels of 3alpha-diol G were associated with an increased risk, but only in men with the L/L or V/L genotype (OR, 2.16; 95% CI, 1.31-3.56). The increase in risk in L/L and V/L men was restricted to aggressive tumors. Our study observed that only in men with the L/L or V/L genotype were increased serum levels of DHEAS and 3alpha-diol G positively associated with a higher risk of aggressive prostate cancer. Free estradiol levels were negatively associated with risk of aggressive prostate cancer in men with the V/V genotype. However, the absence of an overall association between V89L genotype and aggressive prostate cancer argues for a cautious interpretation of these observations.     

Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden)

Objective: High levels of sex steroid hormones and prolactin have been suggested to enhance breast cancer development. Low levels of SHBG may indicate high levels of (bio-available) steroid hormones. The present study investigates whether high levels of sex steroid hormones and prolactin, and/or low levels of SHBG, are associated with high breast cancer risk. Methods: Blood samples were collected in about 65,000 women participating in two population-based prospective cohort studies in Sweden. Follow-up yielded 173 postmenopausal breast cancer cases who had not been exposed to HRT. Levels of estrone, estradiol, SHBG, FSH, prolactin, testosterone, androstenedione and DHEAs were analysed in cases and 438 controls. Logistic regression analysis yielded odds ratios (ORs), with 95% confidence intervals, adjusted for potential confounders. Results: The risk of breast cancer was associated with the highest versus lowest quartiles of estrone, OR: 2.58 (1.50–4.44), estradiol (dichotomised: high versus low) (1.73: 1.04–2.88), and testosterone (1.87: 1.08–3.25). High risks, although not statistically significant, were seen for androstenedione (1.58: 0.92–2.72) and DHEAs (1.62: 0.89–2.72). No strong associations were seen between SHBG or prolactin and risk of breast cancer. Conclusions: High levels of estrone, estradiol, testosterone, and possibly androstenedione and DHEAs, in postmenopausal women are associated with a high risk of subsequent breast cancer.     

Prenatal and perinatal risk factors and testicular cancer: a hospital-based case-control study

Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight <3000 g (OR = 2.4: 95% CI = 0.7-8.1), and birth weight >4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.     

In utero exposure to female hormones and germ cell tumors in children

BACKGROUND: Maternal exposure to exogenous female hormones during pregnancy has been implicated as a risk factor for malignant germ cell tumors (GCTs) in the offspring in some epidemiologic studies of testicular and ovarian carcinoma in adults. METHODS: From 1996 to 2002, 278 children younger than 15 years of age with malignant GCTs and 423 healthy controls, frequency-matched for geographic location, age, and sex were enrolled in a case-control study to investigate whether in utero exposure to female hormones is associated with the risk of malignant GCT in children. Cases were recruited from 84 institutions in the U.S. and controls were enrolled through random digit dialing. Information was obtained through telephone interview with the biological mothers of the subjects and through blinded review of the mothers' medical records. RESULTS: Neither self-reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to exogenous female hormones was related to malignant GCT risk. Pregnancy-related conditions that may have altered serum levels of circulating female hormones were also unrelated to the risk of GCT in the offspring. CONCLUSION: This study failed to provide strong evidence to support the hypothesis that maternal exposure to exogenous female hormones during pregnancy increases the risk of GCT in the offspring.     

Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer

The present case-control study was undertaken to investigate the association between exposure to maternal hormones and risk of testicular germ-cell cancer by histologic subgroups. Cases were males, aged 16 to 59 years, diagnosed with testicular germ-cell cancer in Ontario between 1987 and 1989. Histologic review was performed on all eligible cases for the purpose of categorizing cases as seminoma or non-seminoma (the latter classified 2 ways, with and without tumors containing seminoma). Risk factor data were collected on 502 cases, 346 case mothers, 975 age-matched controls, and 522 control mothers. Exogenous hormone exposure was associated with elevated risk (OR = 4.9, 95% CI 1.7-13.9). Several additional risk factors were associated with risk of testicular cancer: bleeding and threatened miscarriage (OR = 0.6, 95% CI 0.3-1.0), maternal cigarette smoking (12+ cigarettes/day OR = 0.6, 95% CI 0. 4-1.0). pre-term birth (OR = 1.6, 95% CI 1.0-2.5), and treatment for undescended testicle (OR = 8.0, 95% CI 3.2-20.0). First births were associated with elevated risk (OR = 1.7, 95% CI 1.0-2.8) among mothers below the age of 24 years at conception. There was little evidence that risk factors differed by histologic subgroup. We found evidence that exposure to maternal hormones, particularly estrogens, is associated with testicular germ-cell cancer risk. Not only does exposure to elevated levels (exogenous hormone use, pre-term birth, and first births among young mothers) increase risk but also exposure to relatively lower levels (heavy cigarette consumption and, perhaps, bleeding and threatened miscarriage) may decrease cancer risk.     

The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer

The A2 allele of CYP17 has been associated with polycystic ovarian syndrome, elevated levels of certain steroid hormones in premenopausal women, and increased breast cancer risk. We prospectively assessed the association between the A2 allele of CYP17 and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort. We also evaluated associations between this CYP17 genotype and plasma steroid hormone levels among postmenopausal controls not using hormone replacement to assess the biological significance of this genetic variant. Women with the A2 allele were not at an increased risk of incident breast cancer [OR (odds ratio), 0.85; 95% CI (confidence interval), 0.65-1.12] or advanced breast cancer (OR, 0.84; 95% CI, 0.54-1.32). We did observe evidence that the inverse association of late age at menarche with breast cancer may be modified by the CYP17 A2 allele. The protective effect of later age at menarche was only observed among women without the A2 allele (A1/A1 genotype: for age at menarche > or =13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2 genotypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among controls, we found women with the A2/A2 genotype to have elevated levels of estrone (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14.4%, P = 0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compared with women with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a strong independent risk factor for breast cancer.     

Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations

The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy. The US Government’s right to retain a non-exclusive, royalty free license in and to any copyright is acknowledged.     

Associations of maternal and umbilical cord hormone concentrations with maternal,gestational and neonatal factors (United States)

Objective: Risks of some cancers in adults have been associated with several pregnancy factors, including greater maternal age and birth weight. For hormone-related cancers, these effects are hypothesized to be mediated through higher in utero estrogen concentrations. In addition, racial differences in pregnancy hormone levels have been suggested as being responsible for differences in testicular and prostate cancer risk by race. However, data on hormonal levels related to these characteristics of pregnancy are sparse, particularly those from studies of the fetal circulation. Methods: Estrogen and androgen concentrations were measured in maternal and umbilical cord sera from 86 normal, singleton pregnancies. Results: Birth size measures (weight, length and head circumference) were positively correlated with maternal estriol (r = 0.25–0.36) and with cord DHEAS concentrations (r = 0.24–0.41), but not with estrogens in cord sera. Maternal age was inversely correlated with maternal DHEAS, androstenedione and testosterone concentrations (r = –0.30, –0.25 and –0.30, respectively), but uncorrelated with estrogens in either the maternal or cord circulation. Black mothers had higher androstenedione and testosterone concentrations than white mothers, however, there were no racial differences in any of the androgens in cord sera. Cord testosterone concentrations were higher in mothers of male fetuses, while both maternal and cord concentrations of estriol were lower in these pregnancies. Conclusions: These data demonstrate associations between hormone concentrations and pregnancy factors associated with offspring's cancer risk, however, the hormones involved and their patterns of association differ by whether the maternal or fetal circulation was sampled. Hormone concentrations in the fetal circulation in this study are not consistent with the hypothesis that greater estrogen concentrations in high birth weight babies mediate the positive association with breast cancer risk observed in epidemiologic studies, or with the hypothesis that higher testosterone exposure in the in utero environment of black males explains their higher subsequent prostate cancer risk.     

Viremia during pregnancy and risk of childhood leukemia and lymphomas in the offspring: Nested case–control study

A possible role for infections of the pregnant mother in the development of childhood acute leukemias and lymphomas has been suggested. However, no specific infectious agent has been identified. Offspring of 74,000 mothers who had serum samples taken during pregnancy and stored in a large‐scale biobank were followed up to the age of 15 years (750,000 person years) through over‐generation linkages between the biobank files, the Swedish national population and cancer registers to identify incident leukemia/lymphoma cases in the offspring. First‐trimester sera from mothers of 47 cases and 47 matched controls were retrieved and analyzed using next generation sequencing. Anelloviruses were the most common viruses detected, found in 37/47 cases and in 40/47 controls, respectively (OR: 0.6, 95% CI: 0.2–1.9). None of the detected viruses was associated with leukemia/lymphoma in the offspring. Viremia during pregnancy was common, but no association with leukemia/lymphoma risk in the offspring was found.     

Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case-control study

Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of hormone receptor [estrogen receptor (ER) and/or progesterone receptor (PR)] defined breast cancer. In a case-control study nested within the EPIC cohort (European Prospective Investigation into Cancer and Nutrition), estradiol, testosterone, and sex hormone-binding globulin levels were measured in prediagnostic serum samples from postmenopausal women not using hormone replacement therapy at blood donation. A total of 554 women who developed invasive breast cancer with information on receptor status were matched with 821 control subjects. Conditional logistic regression models estimated breast cancer risk with hormone concentrations according to hormone receptor status of the tumor. Sex steroid hormones were associated with risks of not only ER+PR+ breast cancer [estradiol OR for highest vs. lowest tertile = 2.91 (95% CI: 1.62-5.23), P(trend) = 0.002; testosterone OR = 2.27 (95% CI: 1.35-3.81), P(trend) = 0.002] but also of ER-PR- breast cancer [estradiol OR = 2.11 (95% CI: 1.00-4.46), P(trend) = 0.05; testosterone OR = 2.06 (95% CI: 0.95-4.46), P(trend) = 0.03], with associations appearing somewhat stronger in the receptor-positive disease. Serum androgens and estrogens are associated with risks of both hormone receptor-negative as well as receptor-positive breast tumors. Further research is needed to establish through which molecular pathways, and during which evolutionary stages of development, androgens and estrogens can promote the occurrence of both receptor-positive and -negative clinical breast tumors.     

Nipple Aspirate Fluid Hormone Concentrations and Breast Cancer Risk

Prior reports identify higher serum concentrations of estrogens and androgens as risk factors for breast cancer, but steroids in nipple aspirate fluid (NAF) may be more related to risk. Incident breast cancer cases and mammography controls were recruited. Sex steroids were measured in NAF from the unaffected breasts of cases and one breast of controls. Menopausal status and menstrual cycle phase were determined. NAF steroids were purified by HPLC and quantified by immunoassays. Conditional logistic regression models were used to examine associations between NAF hormones and case-control status. NAF samples from 160 cases and 157 controls were evaluable for hormones. Except for progesterone and dehydroepiandrosterone (DHEA), the NAF and serum concentrations were not significantly correlated. NAF estradiol and estrone were not different between cases and controls. Higher NAF (but not serum) DHEA concentrations were associated with cases, particularly among estrogen receptor (ER)-positive cases (NAF odds ratio (OR)?=?1.18, 95 % confidence interval (CI) 1.02, 1.36). NAF DHEA was highly correlated with NAF estradiol and estrone but not with androstenedione or testosterone. Higher progesterone concentrations in both NAF and serum were associated with a lower risk of ER-negative cancer (NAF OR?=?0.69, 95 % CI 0.51, 0.92). However, this finding may be explained by case-control imbalance in the number of luteal phase subjects (2 cases and 19 controls). The significantly higher concentration of DHEA in NAF of cases and its correlation with NAF estradiol indicates a potentially important role of this steroid in breast cancer risk; however, the negative association of progesterone with risk is tentative.     

Serum hormones and the alcohol-breast cancer association in postmenopausal women

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.     

Maternal Use of Recreational Drugs and Neuroblastoma in Offspring: A Report from the Children’s Oncology Group (United States)

Objective To evaluate whether maternal use of recreational drugs around conception and pregnancy influences the risk of childhood neuroblastoma. Methods Self-reported use of recreational drugs from one month prior to pregnancy until diagnosis was assessed among mothers of 538 children with neuroblastoma (diagnosed 1992–1994 and identified through the Children’s Cancer Group and Pediatric Oncology Group) and 504 age-matched controls (identified by random-digit dialing). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for age at diagnosis and household income. Results Maternal use of any illicit or recreational drug around pregnancy was associated with an increased risk of neuroblastoma in offspring (OR = 1.82, 95% CI: 1.13, 3.00), particularly use of marijuana in the first trimester of pregnancy (OR = 4.75, 95% CI: 1.55, 16.48). Marijuana use in the month before pregnancy did not increase risk. The effect of gestational marijuana exposure was strongest in subjects diagnosed before age one. Evaluation of recreational drugs other than marijuana was limited by infrequent use, and analyses of drug use by fathers were not carried out due to missing data. Conclusions Maternal recreational drug use and marijuana use during pregnancy were associated with increased risk of neuroblastoma in offspring. Further examination of these drugs and the risk of childhood cancer is warranted.     

Serum concentrations of estrogens, sex hormone binding globulin, and androgens and risk of breast hyperplasia in postmenopausal women.

OBJECTIVE: We sought to determine whether serum concentrations of estrogens, androgens, and sex hormone binding globulin in postmenopausal women were related to the presence of mammary hyperplasia, an established breast cancer risk factor. METHODS: Study participants provided serum before breast biopsy or mastectomy in three hospitals in Grand Rapids, Michigan, between 1977 and 1987. A total of 179 subjects with breast hyperplasia were compared with 152 subjects with nonproliferative breast changes that are not associated with increased breast cancer risk. RESULTS: The odds ratios (OR) associated with the three upper quartiles of estradiol in comparison with the lowest quartile were 2.2 [95% confidence interval (95% CI) 1.1-4.6], 2.5 (95% CI, 1.1-5.3), and 4.1 (95% CI, 2.0-8.5; Ptrend = 0.007). The corresponding ORs for bioavailable estradiol, estrone, and estrone sulfate were of generally similar magnitude (Ptrend = 0.003 for bioavailable estradiol, 0.0004 for estrone, and 0.0009 for estrone sulfate). Relative to women concurrently in the lowest tertile for serum estradiol, estrone, and estrone sulfate, women concurrently in the highest tertile for all three hormones had an OR of 5.8 (95% CI, 2.2-15.2). Serum concentrations of sex hormone binding globulin, testosterone, dehydroepiandrosterone, androstenedione, and androstenediol were not associated with risk of hyperplasia. CONCLUSIONS: Serum concentrations of estrogens, but not of androgens or sex hormone binding globulin, were strongly and significantly associated with risk of breast hyperplasia in postmenopausal women, suggesting that estrogens are important early in the pathologic process towards breast cancer.