Project description:BackgroundDouching was recently reported to be associated with elevated levels of urinary metabolites of endocrine disrupting phthalates, but there is no literature on douching in relation to ovarian cancer. Numerous case-control studies of genital talc use have reported an increased risk of ovarian cancer, but prospective cohort studies have not uniformly confirmed this association. Behavioral correlation between talc use and douching could produce confounding.MethodsThe Sister Study (2003-2009) enrolled and followed 50,884 women in the US and Puerto Rico who had a sister diagnosed with breast cancer. At baseline, participants were asked about douching and talc use during the previous 12 months. During follow-up (median of 6.6 years), 154 participants reported a diagnosis of ovarian cancer. We computed adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer risk using the Cox proportional hazards model.ResultsThere was little association between baseline perineal talc use and subsequent ovarian cancer (HR: 0.73, CI: 0.44, 1.2). Douching was more common among talc users (odds ratio: 2.1, CI: 2.0, 2.3), and douching at baseline was associated with increased subsequent risk of ovarian cancer (HR: 1.8, CI: 1.2, 2.8).ConclusionsDouching but not talc use was associated with increased risk of ovarian cancer in the Sister Study.
Project description:BackgroundMultiple studies of ovarian cancer and genital talc use have led only to consensus about possible carcinogenicity. Seeking greater clarity, we examined this association in 2,041 cases with epithelial ovarian cancer and 2,100 age- and-residence-matched controls.MethodsWe defined genital talc use as regular application to the genital/rectal area directly, on sanitary napkins, tampons, or underwear. To estimate "talc-years," we multiplied applications per year by years used. Unconditional logistic regression, Wald statistics, likelihood-ratio tests, and polytomous logistic regression were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI), trends, effect-modification, and heterogeneity by ovarian cancer histologic subtype.ResultsOverall, genital talc use was associated with an OR (95% CI) of 1.33 (1.16, 1.52), with a trend for increasing risk by talc-years. Women who used talc were more likely to be older, heavier, asthma sufferers, and regular analgesic users--none of which was a confounder. Dose-responses were more apparent for premenopausal women, especially nonsmokers and those heavier or postmenopausal users of menopausal hormones (hormone therapy [HT]). Subtypes of ovarian cancer more likely to be associated with talc included invasive serous and endometrioid tumors and borderline serous and mucinous tumors. Premenopausal women and postmenopausal HT users with these subtypes who had accumulated >24 talc-years had ORs (95% CI) of 2.33 (1.32, 4.12) and 2.57 (1.51, 4.36), respectively.ConclusionRisks for epithelial ovarian cancer from genital talc use vary by histologic subtype, menopausal status at diagnosis, HT use, weight, and smoking. These observations suggest that estrogen and/or prolactin may play a role via macrophage activity and inflammatory response to talc.
Project description:This paper describes data from a systematic review and meta-analysis [1] conducted to identify and evaluate published peer reviewed evidence on the association between perineal use of talc powder and risk of ovarian cancer. These data were collected from multiple electronic bibliographic databases, as well as from grey literature sources, without applying time, language or other filters. A meta-analysis was conducted to quantitatively assess the ovarian cancer risk in relation to talc use and other potential risk factors.
Project description:ObjectiveTo assess recall bias by evaluating how well female cancer survivors remember details regarding their cancer diagnosis, treatment, and fertility preservation (FP) counseling.Oncofertility literature cites recall bias as a pitfall of retrospective surveys, but limited data exist to quantify this bias.DesignRetrospective secondary analysis of cross-sectional survey data.SettingSingle academic medical center.PatientsFemale oncology patients of reproductive age, 18-44 years old, at least 6 months past their last chemotherapy treatment.InterventionsNot applicable.Main outcome measuresRecall of details surrounding cancer diagnosis and chemotherapy regimens, recall of FP counseling and ovarian reserve testing, and rates of chart-documented FP counseling.ResultsIn total, 117 patients completed the survey, with 112 verified via chart review. When asked to report the chemotherapy regimen, 57% (64 of the 112) marked "I don't know/prefer not to say." Regarding FP, 80% (90 of the 112) denied being offered counseling. Of the 37 (33%) who had documented FP conversations, 13 (35%) did not recall mention of fertility. Only 2 of 8 patients with ovarian reserve testing recalled this being performed at their initial visit. Multivariable logistic regression revealed older age was significantly associated with not being offered FP (odds ratio [OR] 0.87).ConclusionsOur results confirm that the accuracy of oncology patients' reporting is limited by a poor recall, particularly regarding their specific chemotherapy regimen. More than 1 in 3 patients documented to have been offered FP counseling do not recall this discussion. Importantly, only one-third of cancer survivors had chart-documented FP counseling. Increased efforts are needed to ensure adequate follow-up beyond the initial visit.
Project description:Talc and titanium dioxide are naturally occurring water-insoluble mined products usually available in the form of particulate matter. This study was prompted by epidemiological observations suggesting that perineal use of talc powder is associated with increased risk of ovarian cancer, particularly in a milieu with higher estrogen. We aimed to test the effects of talc vs. control particles on the ability of prototypical macrophage cell lines to curb the growth of ovarian cancer cells in culture in the presence of estrogen. We found that murine ovarian surface epithelial cells (MOSEC), a prototype of certain forms of ovarian cancer, were present in larger numbers after co-culture with macrophages treated to a combination of talc and estradiol than to either agent alone or vehicle. Control particles (titanium dioxide, concentrated urban air particulates or diesel exhaust particles) did not have this effect. Co-exposure of macrophages to talc and estradiol has led to increased production of reactive oxygen species and changes in expression of macrophage genes pertinent in cancer development and immunosurveillance. These findings suggest that in vitro exposure to talc, particularly in a high-estrogen environment, may compromise immunosurveillance functions of macrophages and prompt further studies to elucidate this mechanism.
Project description:Epidemiologic evidence suggests a possible association between genital use of talcum powder and risk of epithelial ovarian cancer; however, the biological basis for this association is not clear. We analyzed interactions between talc use and genes in detoxification pathways [glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and N-acetyltransferase 2 (NAT2)] to assess whether the talc/ovarian cancer association is modified by variants of genes potentially involved in the response to talc. Our analysis included 1,175 cases and 1,202 controls from a New England-based case-control study and 210 cases and 600 controls from the prospective Nurses' Health Study. We genotyped participants for the GSTM1 and GSTT1 gene deletions and three NAT2 polymorphisms. We used logistic regression to analyze the main effect of talc use, genotype, and gene-talc interactions in each population and pooled the estimates using a random-effects model. Regular talc use was associated with increased ovarian cancer risk in the combined study population (RR, 1.36; 95% CI, 1.14-1.63; P(trend) < 0.001). Independent of talc, the genes examined were not clearly associated with risk. However, the talc/ovarian cancer association varied by GSTT1 genotype and combined GSTM1/GSTT1 genotype. In the pooled analysis, the association with talc was stronger among women with the GSTT1-null genotype (P(interaction) = 0.03), particularly in combination with the GSTM1-present genotype (P(interaction) = 0.03). There was no clear evidence of an interaction with GSTM1 alone or NAT2. These results suggest that women with certain genetic variants may have a higher risk of ovarian cancer associated with genital talc use. Additional research is needed on these interactions and the underlying biological mechanisms.
Project description:Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high-throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with postexcision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics and provides insights not readily obtainable from such approaches.
Project description:BackgroundEpidemiologic studies of fecundability often use retrospectively measured time-to-pregnancy (TTP), thereby introducing potential for recall error. Little is known about how recall error affects the bias and precision of the fecundability odds ratio (FOR) in such studies.MethodsUsing data from the Danish Snart-Gravid Study (2007-12), we quantified error for TTP recalled in the first trimester of pregnancy relative to prospectively measured TTP among 421 women who enrolled at the start of their pregnancy attempt and became pregnant within 12 months. We defined recall error as retrospectively measured TTP minus prospectively measured TTP. Using linear regression, we assessed mean differences in recall error by maternal characteristics. We evaluated the resulting bias in the FOR and 95% confidence interval (CI) using simulation analyses that compared corrected and uncorrected retrospectively measured TTP values.ResultsRecall error (mean = -0.11 months, 95% CI -0.25, 0.04) was not appreciably associated with maternal age, gravidity, or recent oral contraceptive use. Women with TTP > 2 months were more likely to underestimate their TTP than women with TTP ≤ 2 months (unadjusted mean difference in error: -0.40 months, 95% CI -0.71, -0.09). FORs of recent oral contraceptive use calculated from prospectively measured, retrospectively measured, and corrected TTPs were 0.82 (95% CI 0.67, 0.99), 0.74 (95% CI 0.61, 0.90), and 0.77 (95% CI 0.62, 0.96), respectively.ConclusionsRecall error was small on average among pregnancy planners who became pregnant within 12 months. Recall error biased the FOR of recent oral contraceptive use away from the null by 10%. Quantitative bias analysis of the FOR can help researchers quantify the bias from recall error.