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Approximately 0.4-1.3% of the worldwide population is transgender. Although the exact prevalence is unknown, there is an increase in open identification as transgender. Among transgender women (TW), the prostate is retained even after gender-affirmation surgery, thus necessitating ongoing screening for prostate cancer (CaP). However, little is known about CaP screening in this population.To assess our current understanding of CaP incidence and prostate-specific antigen (PSA) screening in TW.We performed a nonsystematic narrative review of all PubMed publications through June 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Given the limited primary research on this subject, case reports were also included. Studies were reviewed to understand PSA screening practices and reports of CaP in this population, as applicable.There is no consensus regarding PSA screening in TW from any of the major societies, and TW are largely absent from guidelines. Case report data suggest that TW with CaP may have more aggressive disease, and these cancers may have been pre-existing prior to present before gender-affirming hormone therapy (GAHT) or be castrate-resistant.We are in the infancy of our understanding of PSA screening in TW. Important avenues for future research include understanding the risks/benefits of PSA screening in TW, how best to mitigate potential negative psychological effects of PSA screening in TW, establishing baseline PSA values for those on GAHT (and determining what values should be considered "elevated"), establishing when to initiate PSA screening for those on GAHT, and establishing the accuracy of biomarkers for those undergoing GAHT.We examined patterns of prostate cancer screening for transgender women. Little is known about prostate cancer incidence or screening in this population. Additional research is needed to establish guidelines for screening in this population.

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time.Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender.Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers.Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and East Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions, and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Cross-tissue analyses indicated that over a third of effector genes most likely act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis, and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article.

Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients; (b) autoimmune diseases and (c) solid organ transplant recipients (SOTR); (2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients; (b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients; (c) SOTR; (d) lupus. Methods: For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy; SOTR; autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co-morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and disease-specific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Results: Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion: Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations. Citation Format: Elham Kazemain, Jane Figueiredo, Jacek Skarbinski, Russell McBride, Viviana Simon, Amy B. Karger, F. Eun-Hyung Lee, Fred R. Hirsch, Andrea Cox, Sabra Klein, Rong Fan, Stephanie Halene, David A. Zidar, James M. Crawford, Bharat Thyagarajan, Charles Gleason, Alex Mathson, Komal Srivastava, Puleng Moshele, Toby Amoss, Martin Runnstrom, Susanne Linderman, Ananda M. Rodilla, Philip C. Mack, Yu Shyr, Anna Yin, Patrick Shea, Jennifer VanOudenhove, Hinnah Siddiqui, Brigid M. Wilson, Eric P. Elkin, Crystal A. Hsiao, Yonah Ziemba, Cheryl B. Schleicher, Sharon Fox, Lawrence H. Kushi, Karen Reckamp, Akil Merchant, Noah Merin. SeroNet Pooling Project of immunocompromised populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 798.