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A review in Science brings together human, animal and genomic research showing that X- and Y-chromosome genes may shape immunity, cancer, aging and other disease risks, in addition to the effects of sex hormones. The findings point to possible implications for diagnosis, treatment and clinical-trial design, but many links remain under investigation.
A review published in Science brings together evidence that genes on the X and Y chromosomes may influence immunity, cancer, aging and other diseases, not just biological sex. The authors say chromosome effects can act alongside sex hormones, with potential implications for how researchers assess disease risk and design treatments and clinical trials.
The review was co-led by Dr. Dan Theodorescu of the University of Arizona Cancer Center and Dr. Dena B. Dubal of the University of California, San Francisco. It synthesizes existing evidence from human studies, mouse models and genomic technologies on chromosome-related processes across the lifespan. The authors discuss links to immune function, metabolism, brain aging, cancer, neurological conditions and cardiometabolic disease.
In women, one X chromosome is largely inactivated early in development, but some genes on it remain active, and others may become active again with age. This can leave some cells with different doses of X-linked genes. The review also describes research into whether the parental origin of the active X matters. In mouse studies, animals whose cells relied mostly on the maternal X showed faster brain aging and memory decline; this finding does not establish the same effect in people.
Chromosome loss is another focus. Loss of an X chromosome in women has been linked to higher leukemia risk, while loss of the Y chromosome in men—often measured in blood—has been associated with cancers, heart disease, severe infections and Alzheimer’s disease. The review says these changes are being studied as possible markers of, and contributors to, age-related disease; the associations do not by themselves prove that chromosome loss causes those conditions.
Why Chromosome Biology Matters
The review broadens a familiar explanation for health differences between women and men. Hormones are not the only factor: genes on the sex chromosomes may also influence how cells function and respond to disease. Understanding those effects could help researchers explain why disease patterns or treatment responses differ among patients.
The potential clinical relevance is not yet a new test or treatment. The authors argue that chromosome-related biology could eventually inform risk assessment, diagnosis and treatment selection. Theodorescu said his laboratory has found that some tumors that lose the Y chromosome can evade immune defenses yet may respond better to immunotherapy. That finding is research evidence, not a recommendation for patients or proof that Y loss predicts an individual’s treatment outcome.
The work also bears on research design. If chromosome-linked differences affect outcomes, trials that account for sex and relevant biological factors may produce evidence that better reflects the people who receive care. The review calls for further investigation before such findings can be translated into routine clinical decisions.
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From Hormones to Chromosomes
Differences in health between men and women have often been discussed in relation to circulating hormones such as estrogen and testosterone. The review does not dismiss hormone effects; it argues that X- and Y-linked genes also have direct roles, working independently and in interaction with hormones.
The paper grew out of discussions at a 2025 National Institute on Aging workshop on sex differences affecting human health across the lifespan, including discussions with Francesca Duncan of Northwestern University. The authors bring together work from multiple fields rather than reporting a single new clinical trial or experiment. Their review, “X and Y chromosomes as determinants of aging and disease,” was published in Science in 2026.
Theodorescu’s earlier research examined Y-chromosome loss in immune cells and cancer cells, including how it could help tumors evade immune responses. Related work from his group has also proposed that Y loss in normal-appearing tissue may signal an area of genetic risk. These prior findings provide context for the review but do not establish that chromosome loss will lead to cancer in a given person.
““In cancer, for example, our laboratory has found that tumors that lose the Y chromosome can evade the immune system, yet may respond better to immunotherapy.””
— Dr. Dan Theodorescu
What the Evidence Cannot Yet Show
The review summarizes evidence of varying kinds and does not show that chromosome differences alone cause the diseases discussed. Many findings are associations or come from mouse research; their relevance to human risk, disease progression and treatment response needs further study. The broader health effects of X-chromosome loss also remain poorly understood.
It is not yet clear which chromosome-related findings can be measured reliably enough to guide care, which patients might benefit from testing, or whether accounting for them would improve outcomes. The source material does not describe a new diagnostic test, treatment guideline or clinical-trial result from this review. The effects may also vary with age, tissue and other biological factors.
Research Needed Before Clinical Use
The authors call for more investigation into how X- and Y-linked genes affect disease across tissues and over a person’s life. Studies will need to test whether reported links hold in human populations and determine when chromosome changes are useful risk markers rather than signs that accompany disease.
Further work can also assess how to include sex-aware questions in clinical research and whether chromosome biology predicts differences in treatment response. Until those questions are answered and findings are validated, the review’s conclusions should be viewed as a research framework, not as a basis for individual diagnosis or treatment choices.
Key Questions
What does the new review say about sex chromosomes?
It synthesizes research suggesting that X- and Y-chromosome genes may influence immunity, cancer, aging and other aspects of health, alongside hormone effects.
Does chromosome loss cause cancer or other diseases?
The review describes associations between chromosome loss and several diseases, including Y-chromosome loss and cancer. An association does not prove causation or predict what will happen to an individual.
Could these findings change cancer treatment?
The authors say chromosome biology could eventually help tailor treatment. Research cited by Theodorescu suggests some Y-loss tumors may evade immune defenses yet respond better to immunotherapy, but this is not a general treatment rule or established guidance for patients.
Are the findings ready to guide personal health decisions?
No new test or clinical guideline is reported in the review. More human research is needed to establish which findings can reliably inform diagnosis, risk assessment or treatment.
Source: rss
