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Simple Summary: The improvement in genetic testing uptake for ovarian cancer faces barriers, such as deficiency in access to genetic testing and counseling, lack of referral, and poor follow-up to completion. Genetic risk information can be utilized to guide risk reduction strategies and management during ovarian cancer treatment. The Genetic Risk Analysis in ovarian CancEr (GRACE) study aimed to evaluate the feasibility of retrospective identification ("Traceback") of both individuals diagnosed with ovarian cancer and their families who could benefit from genetic risk information. The GRACE study findings can assist health care systems to implement and increase genetic testing for survivors of ovarian cancer and other hereditary cancers. Background: Recommendations state all people with ovarian cancers (OCs) receive genetic counseling, but testing uptake is only between 15 and 31%. Those with a prior diagnosis of OC who have not received genetic testing represent a missed opportunity for life-saving genetic risk information. The Genetic Risk Analysis in ovarian CancEr (GRACE) study aimed to evaluate the feasibility of the retrospective identification ("Traceback") of individuals diagnosed with OC. Methods: This nonrandomized intervention study within two integrated health care systems identified participants with a history of OC between 1998 and 2020 who did not have genetic testing or testing limited to BRCA1/2. Participants received clinical genomic sequencing via a custom 60 gene panel. This study measured the feasibility of the Traceback methodology in OC survivors. Results: The initial cohort included 929 individuals, of which 57% had no prior genetic testing. Of the 302 eligible for recruitment, 88 consented to participate. We were able to outreach 97% of the eligible population using contact information from medical records. The stage at diagnosis was the only factor associated with consent. Of the 78 who returned their saliva sample, 21% had pathogenic/likely pathogenic variants, and 79% had negative results. Conclusion: The GRACE study resulted in a 29% uptake of genetic testing in OC survivors. The time since diagnosis did not have an impact on consent or ability to contact. GRACE can inform the implementation of future Traceback programs, providing guidance on how to prevent and mitigate the burden of OC and other hereditary cancers. [ABSTRACT FROM AUTHOR]

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Individuals with arteriosclerosis in the large veins of the legs (large-vessel peripheral arterial disease) may have an increased risk of dying from cardiovascular diseases, including coronary artery disease. Of 475 individuals examined for the presence of large-vessel peripheral arterial disease, 67 were diagnosed with the disease. After 10 years, 61.8% of the men and 33.3% of the women with large-vessel peripheral arterial disease had died, compared with 16.9% of the men and 11.6% of the women without the disease. After adjusting for other risk factors for cardiovascular disease, individuals with large-vessel peripheral arterial disease were three times more likely to die from any cause, six times more likely to die from cardiovascular diseases and almost seven times more likely to die from coronary artery disease than individuals without the disease.

The menstrual cycle is an important indicator of underlying hormonal function. Although menstrual cycle variability (sometimes referred to as 'regularity') is associated with a variety of demographic, behavioral, occupational, and environmental factors, as well as with several chronic diseases, few studies have examined its association with fecundity. We investigated whether a woman's menstrual cycle variability was associated with the likelihood of her achieving pregnancy. In this prospective study, we analyzed 3,536 menstrual cycles from 401 women (aged 19-41) recruited from 1990-1994. The women provided daily diaries recording menstrual bleeding, intercourse, and birth control use. Urine samples were assayed for human chorionic gonadotropin to identify early pregnancies during each menstrual cycle. Each woman's menstrual cycle variability was defined by the standard deviation of her cycle lengths during followup. The median follow-up was eight cycles. The outcome was her per-cycle probability of pregnancy. We found that women with high menstrual cycle variability had a reduced (51% lower) per cycle probability of pregnancy (fecundity ratio: 0.49; 95% confidence interval: 0.31, 0.77) compared with women with minimal variability. This relationship was independent of a woman's age and her mean cycle length. Thus, researchers and clinicians using menstrual cycle characteristics as indicators of endocrine or reproductive health should include measures of cycle variability in addition to the more commonly examined cycle length. [ABSTRACT FROM AUTHOR]

The article presents nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) to examine the role of estrogen receptor (ESR2) in modulating carcinogens through gene regulation related to cell proliferation and apoptosis. The materials and methods used are described, as well as the characteristics of the study population. It was discovered that single nucleotide polymorphisms (SNP) in ESR2 were not associated with cancer risk.

Introduction/objective: The objective of this study was to develop an algorithm to identify Kaiser Permanente Colorado (KPCO) members with a history of cancer., Background: Tumor registries are used with high precision to identify incident cancer, but are not designed to capture prevalent cancer within a population. We sought to identify a cohort of adults with no history of cancer, and thus, we could not rely solely on the tumor registry., Methods: We included all KPCO members between the ages of 40-75 years who were continuously enrolled during 2013 (N=201,787). Data from the tumor registry, chemotherapy files, inpatient and outpatient claims were used to create an algorithm to identify members with a high likelihood of cancer. We validated the algorithm using chart review and calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for occurrence of cancer., Findings: The final version of the algorithm achieved a sensitivity of 100 percent and specificity of 84.6 percent for identifying cancer. If we relied on the tumor registry alone, 47 percent of those with a history of cancer would have been missed., Discussion: Using the tumor registry alone to identify a cohort of patients with prior cancer is not sufficient. In the final version of the algorithm, the sensitivity and PPV were improved when a diagnosis code for cancer was required to accompany oncology visits or chemotherapy administration., Conclusion: Electronic medical record (EMR) data can be used effectively in combination with data from the tumor registry to identify health plan members with a history of cancer.

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

Background: Estrogen receptor beta (ESR2) may play a role in modulating prostate carcinogenesis through the regulation of genes related to cell proliferation and apoptosis., Methods: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (>or=T3b, N1, or M1) and high-grade (Gleason sum >or=8) prostate cancer, respectively., Results: The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer., Conclusion: In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk under the recessive model could be a chance finding and, in any event, would seem to contribute only slightly to the overall burden of prostate cancer.