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Accounting for sex differences variability in the design of sex-adapted cancer treatments.

ABSTRACT: The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We hypothesized that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- biased extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our translational goal should be adaptation of treatment to the unique mix of sex-biased mechanisms that are present in each patient. To develop a tool that could advance this goal, we applied a Bayesian Nearest Neighbor (BNN) analysis to 8370 cancer transcriptomes from 26 different adult and 4 different pediatric cancer types to establish patient-specific Transcriptomic Sex Indices (TSI). TSI precisely partitions an individual patient's whole transcriptome into female- and male- biased components such that cancer type, patient sex, and transcriptomics, provide a novel and patient-specific mechanistic identifier that can be used for sex-adapted, precision cancer treatment planning.

SUBMITTER: Yang W

PROVIDER: S-EPMC10168521 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Accounting for sex differences variability in the design of sex-adapted cancer treatments.

Yang Wei W Rubin Joshua B JB

medRxiv : the preprint server for health sciences 20230425

The significant sex differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. We hypothesized that one barrier to translation is that sex differences in cancer phenotypes resemble sex differences in height: highly overlapping, but distinct, male and female population distributions that vary continuously between female- and male- biased extremes. A consequence of this variance is that sex-specific treatments are rendered unrealistic, and our trans ...[more]

PMID: 37162837

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Project description:BackgroundApproximately twice as many females as males are diagnosed with posttraumatic stress disorder (PTSD). However, little is known about why females report more PTSD symptoms than males. Prior studies have generally focused on few potential mediators at a time and have often used methods that were not ideally suited to test for mediation effects. Prior research has identified a number of individual risk factors that may contribute to sex differences in PTSD severity, although these cannot fully account for the increased symptom levels in females when examined individually.ObjectiveThe present study is the first to systematically test the hypothesis that a combination of pre-, peri-, and posttraumatic risk factors more prevalent in females can account for sex differences in PTSD severity.MethodThe study was a quasi-prospective questionnaire survey assessing PTSD and related variables in 73.3% of all Danish bank employees exposed to bank robbery during the period from April 2010 to April 2011. Participants filled out questionnaires 1 week (T1, N=450) and 6 months after the robbery (T2, N=368; 61.1% females). Mediation was examined using an analysis designed specifically to test a multiple mediator model.ResultsFemales reported more PTSD symptoms than males and higher levels of neuroticism, depression, physical anxiety sensitivity, peritraumatic fear, horror, and helplessness (the A2 criterion), tonic immobility, panic, dissociation, negative posttraumatic cognitions about self and the world, and feeling let down. These variables were included in the model as potential mediators. The combination of risk factors significantly mediated the association between sex and PTSD severity, accounting for 83% of the association.ConclusionThe findings suggest that females report more PTSD symptoms because they experience higher levels of associated risk factors. The results are relevant to other trauma populations and to other trauma-related psychiatric disorders more prevalent in females, such as depression and anxiety.

Dataset Information

Accounting for sex differences variability in the design of sex-adapted cancer treatments.

Publications

Accounting for sex differences variability in the design of sex-adapted cancer treatments.

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