Can gender play a role in determining cancer treatment choices?

MD Anderson study reveals ‘sex-biased’ gene signatures in review of 13 cancer types
It is well known that men and women differ in terms of cancer susceptibility, survival and mortality, but exactly why this occurs at a molecular level has been poorly understood.

A study at The University of Texas MD Anderson Cancer Center reviewed 13 cancer types and provided a molecular understanding of sex effects in diverse cancers. The research revealed two cancer-type groups associated with cancer incidence and mortality, suggesting a “pressing need” to develop sex-specific therapeutic strategies for some cancers.The research findings are published online issue of Cancer Cell.

Using data from The Cancer Genome Atlas, a team led by Han Liang, Ph.D., associate professor of Bioinformatics and Computational Biology, found more than half of the genes studied that were related to clinical practice of cancer treatment showed sex-biased signatures in certain cancer types.

Our study helps elucidate the molecular basis for sex disparities in cancer and lays a critical foundation for the future development of precision cancer medicine that is sex-specific,” said Liang. “This is a crucial finding as currently, male and female patients with many cancer types often are treated in a similar way without explicitly considering their gender.

Liang’s group performed a comprehensive analysis of molecular differences between male and female patients, revealing two sex-effect groups associated with distinct incidence and mortality profiles and accounting for 53 percent of clinically actionable genes. Those genes are informative for clinical decisions and are either therapeutic targets or biomarkers that can help predict patient survival or tumor response.
In the study, Liang found one group contained a small number of sex-affected genes (weak group), while the other showed a much greater number of sex-biased molecular signatures (strong group). Liang said the current equal treatment of both genders may be appropriate for those in the “weak” group, but observations in the “strong” group are clinically significant.

Special consideration should be given to those in the strong sex-effect group in terms of both drug development and practice,” said Liang. “For a therapeutic target with a strong sex-biased signature, sex-specific clinical trials may be more likely to succeed. This new information is vital as the fundamental issue of sex differences for cancer prevention and therapy has not been investigated systematically.

Liang’s team analyzed data in patient cohorts of 30 or greater samples for each sex for various cancers of the bladder, colon, kidney, brain, rectum, thyroid, liver and lung as well as acute myeloid leukemia. They looked for specific molecular data including somatic mutations, copy alterations, protein and gene expression and DNA methylation. The study included controls for other factors such as race, age, disease stage, smoking status and tumor purity.

Interestingly, our analysis also suggested that sex bias might be amplified during the tumor formation process,” said Liang. “However this observation should be interpreted with caution at this early stage as further efforts are needed to determine the relative contributions of other factors, including tumorigenesis, sex chromosomes and hormones.”

Yuan et al. Comprehensive characterization of molecular differences in cancer between male and female patients. Cancer Cell, 2016;29:711–722 DOI: http://dx.doi.org/10.1016/j.ccell.2016.04.001 [Abstract]

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Cancer may drive health problems as people age

A new study indicates that cancer may have negative impacts on both the physical and mental health of individuals as they age. Published in CANCER, a peer-reviewed journal of the American Cancer Society, the study suggests that cancer increases the risk for certain health issues above and beyond normal ageing. This is likely due, in part, to decreased physical activity and stress associated with cancer diagnosis and treatment.

As the population of older adults grows, it is increasingly important for clinicians to understand the unique impact of cancer on the health of individuals as they age. To investigate, Corinne Leach, MS, PhD, MPH, of the American Cancer Society in Atlanta, and her colleagues analysed cancer registry data that were linked to Medicare surveys. The analysis included 921 Medicare beneficiaries with a breast, colorectal, lung, or prostate cancer diagnosis who completed initial surveys in 1998 and 2001 and follow-up surveys two years later. These patients were matched to 4605 controls without cancer.

Cancer groups demonstrated greater declines in activities of daily living and physical function compared with controls, with the greatest change for lung cancer patients. Having a cancer diagnosis increased risk for depression but did not increase the likelihood of developing arthritis, incontinence (except for prostate cancer), or vision/hearing problems. Having a cancer diagnosis also did not exacerbate the severity of arthritis or foot neuropathy.

This prospective analysis used a propensity score matched control group to cancer cases that enabled us to tease apart the effects of cancer and ageing in a novel way,” said Dr. Leach. “Decreased physical functioning among older cancer patients compared with older adults without cancer is an important finding for clinicians because it is also actionable. Clinicians need to prepare patients and families for this change in functioning levels and provide interventions that preserve physical function to limit the declines for older cancer patients.”

Leach et al. “Is it my cancer or am I just getting older?: Impact of cancer on age-related health conditions of older cancer survivors.” Cancer, 2016; DOI: 10.1002/cncr.29914 [Abstract]