Influence of family history on penetrance of hereditary cancers in a population setting.
Leigh Jackson et al. EClinicalMedicine 2023 11 102159
From the abstract: "Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) "
Personalized Initial Screening Age for Colorectal Cancer in Individuals at Average Risk.
Xuechen Chen et al. JAMA Netw Open 2023 10 (10) e2339670
From the abstract: "How can risk variation in individuals without a family history of colorectal cancer (CRC) be translated into personalized starting ages of screening? In this cohort study of 242?779 participants with no previous screening for and no family history of CRC, derivation of risk-adapted starting ages of screening used 2 major CRC risk indicators, sex and a polygenic risk score (PRS), based on the risk advancement period concept. Risk-adapted starting ages varied by as much as 24 years between men in the highest PRS decile and women in the lowest PRS decile, even among individuals at average risk. "
Multitarget Stool RNA Test for Colorectal Cancer Screening.
Erica K Barnell et al. JAMA 2023 10
From the abstract: " What is the performance of the novel multitarget stool RNA (mt-sRNA) test (ColoSense) for individuals 45 years and older undergoing colorectal cancer screening? A pivotal prospective, cross-sectional clinical trial comprising 8920 eligible participants was used to evaluate the sensitivity and specificity of the mt-sRNA test compared with a colonoscopy. The sensitivity of the mt-sRNA test for detecting colorectal cancer was 94%, the sensitivity for detecting advanced adenomas was 46%, and the specificity for no lesions on colonoscopy was 88%."
Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians.
Hiroshi Y Yamada et al. NPJ Precis Oncol 2023 8 (1) 79
We compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1).