JNCI Journal of the National Cancer Institute最新文献

Background: Whether carriers of BRCA1 or BRCA2 (BRCA1/2) pathogenic variants (PVs) have increased risks of childhood, adolescent, and young adult (CAYA) cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1/2 PV carriers and genetic testing for CAYA cancer patients.

Methods: Using data from 47,117 individuals from 3,086 BRCA1/2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30.

Results: Our data included 274 cancers diagnosed before age 30: 139 breast cancers, 10 ovarian cancers, and 125 non-breast non-ovarian cancers. Associations for breast cancer in young adulthood (20-29 years) were found with RRs of 11.4 (95% CI: 5.5, 23.7) and 5.2 (95% CI: 1.6, 17.7) for BRCA1 and BRCA2 PV carriers, respectively. No association was found for any other investigated CAYA cancer, nor for all non-breast non-ovarian cancers combined: the RRs were 0.4 (95% CI: 0.1, 1.4) and 1.4 (95% CI: 0.7, 3.0) in BRCA1 or BRCA2 PV carriers, respectively.

Conclusion: We found no evidence that BRCA1/2 PV carriers have an increased CAYA cancer risk aside from breast cancer in women in their 20's. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1/2 PV would be low (ie, RR < 2) if it existed. Our findings do not support PV testing for offspring of BRCA1/2 PV carriers at ages <18 years, nor for conducting BRCA1/2 PV testing for childhood and adolescent cancer patients.

Background: Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents high-grade serous carcinoma (HGSC) in BRCA1/2 germline pathogenic variant (GPV) carriers. Still, some women develop HGSC after RRSO without pathologic findings. This study assessed long-term incidence and risk factors for developing HGSC after RRSO without pathologic findings.

Methods: BRCA1/2 GPV carriers were selected from Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) cohort. Follow-up data for HGSC after RRSO were obtained from the Dutch Nationwide Pathology Databank (PALGA) and confirmed by histopathological review. Cumulative incidence rates of HGSC were calculated using Kaplan-Meier analyses. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with an increased risk of HGSC following RRSO without pathologic findings.

Results: A total of 2519 women were included, with a median follow-up of 13.4 years (range: 0.0-27.6). The 20-years cumulative incidence rate of HGSC was 1.5% (95% CI: 0.0-2.1) for BRCA1 and 0.2% (95% CI: 0.0-1.4) for BRCA2 GPV carriers. All women who developed HGSC underwent RRSO after the recommended age. Incomplete embedding of the RRSO specimen (HR: 4.2, 95% CI: 1.4-12.6), higher age at RRSO (HR per year: 1.1, 95% CI: 1.0-1.1), and carrying a BRCA1 GPV (HR: 12.1, 95% CI: 1.6-91.2) were associated with increased risk of HGSC.

Conclusions: In BRCA1/2 GPV carriers, long-term incidence of HGSC after RRSO without pathologic findings was low. Strict adherence to guidelines regarding timely RRSO followed by complete specimen embedding can further reduce the risk of HGSC in the years following RRSO.

Background: Rising cancer incidence, particularly for colorectal cancer, has been reported in young adults. This study examined whether this is related to an increase in mortality.

Methods: We analysed World Health Organization (WHO) mortality data among young adults aged 25-49 in 15 most populous upper-middle and high-income countries from 1990 to 2021 with reliable data. Mid-year populations were retrieved from the United Nations for the American Countries and from the WHO for the other countries. We compared age-standardised mortality rates (ASMRs) in 2019-2021 to 2009-2011 and performed joinpoint regression analysis for all cancers and selected most common cancer sites: colorectum, pancreas, lung and breast.

Results: In 2019-2021, the highest ASMRs (per 100,000) were in Romanian males (38.6) and Argentinian females (45.9), while the lowest ones in Japan (males: 16.3; females: 22.7). ASMRs for colorectal cancers increased in 2019-2021 compared to 2009-2011 in nine countries among men and in seven countries among women. The highest increases were in the UK (males: +26.1%; females: +33.7%), Canada (males: +25.3%), and Mexico (males: +33.5%; females: +29.7%). Long-term analysis over the last three decades showed declining trends in total cancer mortality in the majority of countries, in lung cancer mortality across all countries, and in breast cancer in all countries except in Latin America.

Conclusions: While mortality from common cancers has generally decreased over the past three decades, mortality from colorectal cancer has increased in some countries. This highlights the need to control the obesity epidemic and implement targeted surveillance strategies in young populations.

Background & aims: Liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) accurately assesses fibrosis. We aimed to develop a universal risk score for predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis.

Methods: We systematically selected predictors and developed the risk prediction model (HCC-LSM) in the HBV training cohort (n = 2,251, median follow-up of 3.2 years). The HCC-LSM model was validated in an independent HBV validation cohort (n = 1,191, median follow-up of 5.7 years) and a non-viral chronic liver disease (CLD) extrapolation cohort (n = 1,189, median follow-up of 3.3 years). A HCC risk score was then constructed based on a nomogram. An online risk evaluation tool (LEBER) was developed using ChatGPT4.0.

Results: Eight routinely available predictors were identified, with LSM levels showing a significant dose-response relationship with HCC incidence (P < .001 by log-rank test). The HCC-LSM model exhibited excellent predictive performance in the HBV training cohort (C-index = 0.866) and the HBV validation cohort (C-index = 0.852), with good performance in the extrapolation CLD cohort (C-index = 0.769). The model demonstrated significantly superior discrimination compared to six previous models across the three cohorts. Cut-off values of 87.2 and 121.1 for the HCC-LSM score categorized participants into low-, medium-, and high-risk groups. An online public risk evaluation tool (LEBER; http://ccra.njmu.edu.cn/LEBER669.html) was developed to facilitate the use of HCC-LSM.

Conclusion: The accessible, reliable risk score based on LSM accurately predicted HCC development in patients with chronic hepatitis, providing an effective risk assessment tool for HCC surveillance strategies.