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Background: Postmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify prediagnostic levels of seven markers related to endogenous hormone metabolism. Methods: Hormones were quantified in baseline serum collected from postmenopausal women in a cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT). Women using exogenous hormones at baseline (1992-1993) were excluded. Incident endometrial (n = 65) and ovarian (n = 67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate cancer risk. Results: Circulating progesterone levels were not associated with endometrial [tertile (T)3 vs. T1 HR (95% confidence interval): 1.87 (0.85-4.11); Ptrend = 0.17] or ovarian cancer risk [1.16 (0.58-2.33); 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs. T1: 0.29 (0.09-0.95); 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18-0.91); 0.03] and positively associated with ovarian cancer risk [3.11 (1.39-6.93); 0.01]. Conclusions: Using sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer. Impact: While our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers. [ABSTRACT FROM AUTHOR]

Background: The role of progestogens in colorectal cancer development is poorly characterized. To address this, our group developed a highly sensitive assay to measure concentrations of seven markers of endogenous progestogen metabolism among postmenopausal women. Methods: The markers were measured in baseline serum collected from postmenopausal women in a case-cohort study within the breast and bone follow-up to the fracture intervention trial (B~FIT). We followed women not using exogenous hormones at baseline (1992-1993) for up to 12 years: 187 women with incident colorectal cancer diagnosed during follow-up and a subcohort of 495 women selected on strata of age and clinical center. We used adjusted Cox regression models with robust variance to estimate risk for colorectal cancer [hazard ratios (HR), 95% confidence intervals (CI)]. Results: High concentrations of pregnenolone and progesterone were not associated with colorectal cancer [quintile(Q)5 versus Q1: pregnenolone HR, 0.71, 95% CI, 0.40-1.25; progesterone HR, 1.25; 95% CI, 0.71-2.22]. A trend of increasing risk was suggested, but statistically imprecise across quintiles of 17-hydroxypregnenolone (Q2 to Q5 HRs, 0.75-1.44; Ptrend, 0.06). Conclusions: We used sensitive and reliable assays to measure multiple circulating markers of progestogen metabolism. Progestogens were generally unassociated with colorectal cancer risk in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Large-scale cancer epidemiology cohorts (CEC) have successfully collected, analyzed, and shared patient-reported data for years. CECs increasingly need to make their data more findable, accessible, interoperable, and reusable, or FAIR. How CECs should approach this transformation is unclear. Methods: The California Teachers Study (CTS) is an observational CEC of 133,477 participants followed since 1995-1996. In 2014, we began updating our data storage, management, analysis, and sharing strategy. With the San Diego Supercomputer Center, we deployed a new infrastructure based on a data warehouse to integrate and manage data and a secure and shared workspace with documentation, software, and analytic tools that facilitate collaboration and accelerate analyses. Results: Our new CTS infrastructure includes a data warehouse and data marts, which are focused subsets from the data warehouse designed for efficiency. The secure CTS workspace utilizes a remote desktop service that operates within a Health Insurance Portability and Accountability Act (HIPAA)- and Federal Information Security Management Act (FISMA)-compliant platform. Our infrastructure offers broad access to CTS data, includes statistical analysis and data visualization software and tools, flexibly manages other key data activities (e.g., cleaning, updates, and data sharing), and will continue to evolve to advance FAIR principles. Conclusions: Our scalable infrastructure provides the security, authorization, data model, metadata, and analytic tools needed to manage, share, and analyze CTS data in ways that are consistent with the NCI's Cancer Research Data Commons Framework. Impact: The CTS's implementation of new infrastructure in an ongoing CEC demonstrates how population sciences can explore and embrace new cloud-based and analytics infrastructure to accelerate cancer research and translation. [ABSTRACT FROM AUTHOR]

Background: Like other cancer epidemiologic cohorts, the California Teachers Study (CTS) has experienced declining participation to follow-up questionnaires; neither the reasons for these declines nor the steps that could be taken to mitigate these trends are fully understood. Methods: The CTS offered their 6th study questionnaire (Q6) in the fall of 2017 using an integrated, online system. The team delivered a Web and mobile-adaptive questionnaire to 45,239 participants via e-mail using marketing automation technology. The study's integrated platform captured data on recruitment activities that may influence overall response, including the date and time invitations and reminders were e-mailed and the date and time questionnaires were started and submitted. Results: The overall response rate was 43%. Participants ages 65 to 69 were 25% more likely to participate than their younger counterparts (OR = 1.25; 95% CI, 1.18-1.32) and nonwhite participants were 28% less likely to participate than non-Hispanic white cohort members (OR = 0.72; 95% CI, 0.68-0.76). Previous questionnaire participation was strongly associated with response (OR = 6.07; 95% CI, 5.50-6.70). Invitations sent after 2 pm had the highest response (OR = 1.75; 95% CI, 1.65-1.84), as did invitations sent on Saturdays (OR = 1.48; 95% CI, 1.36-1.60). Conclusions: An integrated system that captures paradata about questionnaire recruitment and response can enable studies to quantify the engagement patterns and communication desires of cohort members. Impact: As cohorts continue to collect scientific data, it is imperative to collect and analyze information on how participants engage with the study. [ABSTRACT FROM AUTHOR]

In this issue of Cancer Epidemiology, Biomarkers & Prevention, Gallicchio and colleagues analyze recent rare-cancers research and suggest broad themes for accelerating progress in this important area. Whether the type of portfolio creation and portfolio management strategies that have worked for common cancers also work best for rare cancers warrants asking. This commentary argues for consideration of additional approaches. Incorporating principles and successes from large-scale network-based clinical trials and from advocacy-based research, and new ways to approach consortia, might accelerate the quantity and improve the quality of future rare-cancer research. Rare cancers significantly influence the overall cancer burden and cancer disparities. Creative community-based approaches to improve rare-cancers research should be considered. [ABSTRACT FROM AUTHOR]

Background: A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women. Methods: We followed 15,595 women (ages 55-80 years) enrolled in the Breast and Bone Follow-up to the Fracture Intervention Trial (BFIT) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 colorectal cancer cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position) and by ratios of the groupings using Cox proportional hazards regression models. Results: No significant associations were seen for estrone (HRQ4 vs. Q1 = 1.15; 95% CI, 0.69-1.93; Ptrend = 0.54), estradiol (HRQ4 vs. Q1 = 0.98; 95% CI, 0.58-1.64; Ptrend > 0.99), or total EM (the sum of all EM; HRQ4 vs. Q1 = 1.35; 95% CI, 0.81-2.24; Ptrend = 0.33). Most metabolites in the 2-, 4-, or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol. Conclusion: Circulating estrogens and their metabolites were generally unrelated to colorectal cancer risk in postmenopausal women. Impact: Additional studies are needed to understand how exogenous estrogen may prevent colorectal cancer. [ABSTRACT FROM AUTHOR]

The article discusses a case-control study which examined the association of circulating adipokine levels with the risk of endometrial cancer among postmenopausal women. Topics discussed include the inverse association of adiponectin levels with endometrial cancer risk, positive association for elevated leptin levels and nonsignificant positive associations for visfatin.

The article discusses research on the link between alcohol consumption and breast cancer risk among postmenopausal women who stopped taking hormone therapy (HT). Background of California Teachers Study participants such as details of their daily alcohol intake and previous HT use is given. The administration of follow-up questionnaires regarding invasive breast cancer diagnosis is reported. The substantial adverse effects of HT and alcohol on breast cancer risk are also explored.

The article reports on the California Teacher Study (CTS) which examined hormone therapy (HT) use in relation to lung cancer risk among postmenopausal women between 1995 and 2007. The Multivariable Cox proportional hazards regression models are described as the methods used, with age as the time metric. Results show that recent or past HT use, whether estrogen alone or with progestin, and taking into consideration the women's menopausal status and smoking history, is not associated with lung cancer risk.

The article discusses a study which evaluated the hypothesis that the genetic risk factors of obesity and diabetes and the risk of endometrial cancer. The authors genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in fat mass and obesity-associated gene (FTO) and hematopoietically-expressed homeobox protein (HHEX) in a primary set of 417 endometrial cancer cases. It was found that there was no association between endometrial cancer and the phenotypes.

The article presents a study which aims to look on the correlation of androgen receptor (AR) genetic variation and the risk of acquiring endometrial cancer. Researchers have conducted an assessment by measuring the haplotype-tagging single nucleotide polymorphisms (htSNP) found in AR and found insignificant correlation. Moreover, the said study has provided meager proof on the link between AR genetic variation and the risk of the mentioned cancer.

The article focuses on the study which investigates the association between physical activity and postmenopausal breast cancer risk in women in the U.S. It states that the study used Cox regression to estimate the relative risk (RR) and 95 percent confidence interval of postmenopausal breast cancer overall and by tumor characteristics. The study concluded that physical activity was associated with reduced postmenopausal breast cancer risk, particularly to estrogen receptor (ER)-negative tumors.

The article presents a pooled analysis which tests the hypothesis whether the presence of one or both A alleles in the single nucleotide polymorphisms (SNP) results in an increased endometrial cancer risk. It notes that common CYP19A1 variants are linked with the 10% to 20% increase in the levels of circulating estrogen in postmenopausal women. It analyzes 4,998 endometrial cancer cases and 8,285 controls for ten studies in the Epidemiology of Endometrial Cancer Consortium.

The article focuses on the study regarding the link between menopausal hormone therapy and colorectal cancer risk. It evaluates the relation of colorectal cancer risk with the duration and recency of specific menopausal hormone therapy formulations and regimens among postmenopausal women. The study reveals a decreased risk of colorectal cancer among users of unposed estrogen therapy. It concludes that estrogen plus progestin use is directly associated with colorectal cancer risk reduction.

The article examines the effects of estrogen therapy (ET) and estrogen plus progestin therapy (EPT) on breast cancer risk. It shows that both ET and EPT are associated with breast cancer risks with the magnitude of increase varying according to body mass and clinical characteristics of the tumors. The article analyzes data from 126,638 females ages 50 to 71 years at baseline.

The article focuses on the associations of height, body mass index (BMI), and the risk of ovarian cancer. According to previous studies, there are inconsistent results with the association of ovarian cancer and body measurements. The study concludes that BMI is not a risk to cancer to postmenopausal women but does pose as a hazard to perimenopausal women as well as height.

The article discusses a cohort study on the association of both obesity and menopausal estrogen therapy with endometrial cancer risk. The study noted that high body mass index (BMI) at baseline and adult weight gain were related with increased endometrial cancer risk and the said association is stronger among nonusers than among current or former users of menopausal hormones. According to the proponents, their findings suggest that the factors increase the risk through common etiologic pathways.

OBJECTIVE: Although human papillomavirus causes essentially all cervical carcinoma, cofactors may differ by cancer histologic type. We examined human papillomavirus genotypes and sexual and reproductive risk factors for cervical adenocarcinoma and squamous cell carcinoma. STUDY DESIGN: One hundred twenty-four women with adenocarcinoma, 139 women with squamous cell carcinoma, and 307 control subjects participated in this case-control study. Logistic regression analyses were performed to calculate odds ratios and CIs. RESULTS: Human papillomavirus 18 was associated most strongly with adenocarcinoma (odds ratio, 105; 95% CI, 23-487). Human papillomavirus 16 was associated most strongly with squamous cell carcinoma (odds ratio, 30; 95% CI, 12-77). More than three lifetime sexual partners was a risk factor for adenocarcinoma (odds ratio, 2.1; 95% CI, 1.1-4.0) and squamous cell carcinoma (odds ratio, 3.0; 95% CI, 1.6-5.9). Even being pregnant was associated inversely with adenocarcinoma (odds ratio, 0.4; 95% CI, 0.2-0.8). Five or more pregnancies was associated with squamous cell carcinoma (odds ratio, 2.2; 95% CI, 0.9-5.4). CONCLUSION: The relative importance of human papillomavirus genotypes 16 and 18 and the reproductive co-factor differences suggest distinct causes for cervical adenocarcinoma and squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

This article offers insights about the link between hormones and breast cancer. Endogenous hormones has been recognized as one of the risk factors for breast cancer. The severity of menopausal symptoms, one of the major predictors of hormone use, is also linked to breast cancer risk. Findings from the Nurses' Health Study supported the notion of a long latency period for chemicals that affect breast cancer risk.

The author reflects on the link between ovarian cancer and menopausal hormone therapy. He notes that recent evidence of studies indicated that current or long-duration use of the hormone therapy increases ovarian cancer risk by 50 percent to 100 percent. He commends the study conducted by Rossing and colleagues which proposed that estrogen and progesterone play opposing mechanistic roles in ovarian carcinogenesis.