Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999-2004

BACKGROUND. Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. OBJECTIVE. We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20-54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS. We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS. Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77-2.41) for endometriosis, 1.56 (95% CI, 0.93-2.61) for leiomyomata, and 1.71 (95% CI, 1.07-2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19-1.02) for endometriosis, 0.63 (95% CI, 0.35-1.12) for leiomyomata, and 0.59 (95% CI, 0.37-0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for MEP and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation. CONCLUSION. The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

Meat consumption and risk of breast cancer in the UK Women's Cohort Study

We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86–1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86–1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14–2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer

Breast-feeding and risk of epithelial ovarian cancer.

Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype

Can weight loss prevent cancer?

We review and update evidence on obesity, weight gain and weight loss in relation to leading cancers since the International Agency for Research on Cancer report of 2002. Emphasis is placed on the time course of disease and implications for weight control to prevent cancer. We conclude that weight loss could prevent a major portion of common cancers

Serum and follicular fluid organochlorine concentrations among women undergoing assisted reproduction technologies

<p>Abstract</p> <p>Background</p> <p>Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error.</p> <p>Methods</p> <p>The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(<it>p</it>-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women.</p> <p>Results</p> <p>Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentrations between samples collected between years 1994–1998 and those collected in 1999–2003.</p> <p>Conclusion</p> <p>Our results support the use of a single serum sample to adequately represent a more biologically relevant dose (concentrations in follicular fluid), as well as exposure levels over time, in epidemiological studies of ART outcomes in relation to organochlorine exposure.</p

Risk prediction models with incomplete data with application to prediction of estrogen receptor-positive breast cancer: prospective data from the Nurses' Health Study

Introduction A number of breast cancer risk prediction models have been developed to provide insight into a woman\u27s individual breast cancer risk. Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk, whether the addition of estradiol levels adds significantly to a model\u27s predictive power has not previously been evaluated. Methods Using linear regression, the authors developed an imputed estradiol score using measured estradiol levels (the outcome) and both case status and risk factor data (for example, body mass index) from a nested case-control study conducted within a large prospective cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study. Results The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz log-incidence model for breast cancer risk prediction within the larger Nurses\u27 Health Study cohort. The follow-up was from 1980 to 2000; during this time, 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed. The addition of imputed estradiol levels significantly improved risk prediction; the age-specific concordance statistic increased from 0.635 ± 0.007 to 0.645 ± 0.007 (P \u3c 0.001) after the addition of imputed estradiol. Conclusion Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman\u27s individual risk of breast cancer

The association of mammographic density with ductal carcinoma in situ of the breast: the Multiethnic Cohort

INTRODUCTION: It is well established that women with high mammographic density are at greater risk for breast cancer than are women with low breast density. However, little research has been done on mammographic density and ductal carcinoma in situ (DCIS) of the breast, which is thought to be a precursor lesion to some invasive breast cancers. METHOD: We conducted a nested case-control study within the Multiethnic Cohort, and compared the mammographic densities of 482 patients with invasive breast cancer and 119 with breast DCIS cases versus those of 667 cancer-free control subjects. A reader blinded to disease status performed computer-assisted density assessment. For women with more than one mammogram, mean density values were computed. Polytomous logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for two measurements of mammographic density: percentage density and dense area. RESULTS: Mammographic density was associated with invasive breast cancer and breast DCIS. For the highest category of percentage breast density (≥50%) as compared with the lowest (<10%), the OR was 3.58 (95% CI 2.26–5.66) for invasive breast cancer and 2.86 (1.38–5.94) for breast DCIS. Similarly, for the highest category of dense area (≥45 cm(2)) as compared with the lowest (<15 cm(2)), the OR was 2.92 (95% CI 2.01–4.25) for invasive breast cancer and 2.59 (1.39–4.82) for breast DCIS. Trend tests were significant for invasive breast cancer (P for trend < 0.0001) and breast DCIS (P for trend < 0.001) for both percentage density and dense area. CONCLUSION: The similar strength of association for mammographic density with breast DCIS and invasive breast cancer supports the hypothesis that both diseases may have a common etiology

Breast cancer susceptibility loci and mammographic density

Introduction Recently, the Breast Cancer Association Consortium (BCAC) conducted a multi-stage genome-wide association study and identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Given the high degree of heritability of mammographic density and its strong association with breast cancer, it was hypothesised that breast cancer susceptibility loci may also be associated with breast density and provide insight into the biology of breast density and how it influences breast cancer risk. Methods We conducted an analysis in the Nurses\u27 Health Study (n = 1121) to assess the relation between 11 breast cancer susceptibility loci and mammographic density. At the time of their mammogram, 217 women were premenopausal and 904 women were postmenopausal. We used generalised linear models adjusted for covariates to determine the mean percentage of breast density according to genotype. Results Overall, no association between the 11 breast cancer susceptibility loci and mammographic density was seen. Among the premenopausal women, three SNPs (rs12443621 [TNRc9/LOC643714], rs3817198 [lymphocyte-specific protein-1] and rs4666451) were marginally associated with mammographic density (p \u3c 0.10). All three of these SNPs showed an association that was consistent with the direction in which these alleles influence breast cancer risk. The difference in mean percentage mammographic density comparing homozygous wildtypes to homozygous variants ranged from 6.3 to 8.0%. None of the 11 breast cancer loci were associated with postmenopausal breast density. Conclusion Overall, breast cancer susceptibility loci identified through a genome-wide association study do not appear to be associated with breast cancer risk