A significance decrease in the incidence was only observed in Whites, but not in Blacks, Hispanics, or Asians/Pacific Islanders. A significance decrease was observed in the incidence of non-squamous cell carcinoma (SCC) rather than SCC among young females 15-24 years from 3 in 2007 to 1.5 in 2013 (APD 9.1, 95% CI 3.1-14.7). Conclusion: A significance decrease in the incidence of cervical cancer during the vaccine era among young females 15-24 years may indicate early effects of HPV vaccination. Further research is needed to confirm this trend.
The problem of the presence of carcinogens in the environment has become of considerable concern to the public, as it has been to the biomedical community for some time. The burden of identifying carcinogenic agents and determining threshold levels, if they exist, falls upon the scientific community. Particular care must be exercised in the design, conduct and analysis of experiments directed toward the identification of carcinogens. The data generated from such tests provides the basis for regulatory decisions by governmental authorities. The advice provided by scientists must be based on sound data. There have been instances, however, and there will be others, in which biological variability and the limits of sensitivity of our tests will give equivocal results. It is the duty of scientists to bring such uncertainties to the attention of the public while working towards the development of more sensitive and precise techniques.
Purpose of study: To identify factors related to the increased risk of neurotoxicity in children with acute lymphoblastic leukemia (ALL) after treatment with the antifolate agent methotrexate (MTX), a critical component of curative protocols. Methods: We analyzed the incidence of and factors associated with acute MTX neurotoxicity (neurologic episode within 14d of dose that resulted in treatment modification) in a multi-site study of 280 (48% Latino) newly diagnosed (between 2012–2017) patients treated on recent pediatric ALL protocols. We examined the effects of genetic ancestry and single nucleotide variants in a subset of 190 patients with genotype data. Results: MTX neurotoxicity occurred in 22% of Latino compared to 7% of non- Latino patients; a nearly 2.5-fold increased risk after accounting for other clinical and demographic factors. Patients with neurotoxicity received fewer total MTX doses, and their risk for relapse was 2-fold higher than patients who did not experience neurotoxicity. We also found that 42% of our Latino patients who experienced a first neurotoxic event went on to have additional events, compared to only 21% of non-Latino patients. The proportion of genetic variation that co-segregates with Native American ancestry was overrepresented in individuals with MTX-related neurotoxicity (mean = 35%) vs without neurotoxicity (mean = 23%, p = 0.025). In multivariable models accounting for sex, age at diagnosis, and treatment risk group, every 10% increase in the proportion of Native American genetic ancestry was associated with a 16% increase in neurotoxicity incidence (HR = 1.16; 95% CI: 1.02–1.32). Our data also suggest that Latinos are at higher risk for first (OR = 3.51, p = 0.02) and subsequent (OR = 6.10, p = 0.04) neurotoxic events associated with a missense variant in TCF12, which is more common in admixed Latino (23%) compared to European (3%) or African (<1%) populations. Conclusions: MTX neurotoxicity is more common among Latino children and adolescents with ALL, compromises treatment efficacy, and may contribute to disparities in ALL relapse and survival. Our findings to date highlight that differences in inherited genetic variation, which segregate with ancestry, likely contribute to disparities in the incidence of treatment-related neurotoxicity.
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