Dawn demeo9/19/2023 ![]() However, controversial findings have been reported as the sex-based differences for immunotherapy response seems to depend on the cohort and cancer type analyzed as well as the immune checkpoint inhibitor agents used and whether they are used in combination with chemotherapy. Poorer response rates are usually reported in females compared to males. There is also a growing literature showing cancer immunotherapy efficacy varies by sex ( 8– 13). Various chemotherapy regimens show higher toxicity, higher response rates, and longer post-treatment survival in women, including lymphoma ( 2), sarcoma ( 3), glioblastoma ( 4), lung ( 5, 6), and colorectal ( 7) cancers. There are significant sex differences in therapeutic response and toxicity for many cancer types. Cancer sites are ordered according to the male-to-female incidence rate ratio starting from cancer sites with higher incidence rates in males compared to females. Bars show the average rate from 2000 to 2017 and 95% confidence interval. Age-adjusted incidence and mortality rates per 100,000 individuals in the US were retrieved from the Surveillance, Epidemiology, and End Results explorer. Despite females having higher incidence for these cancers, they have better survival compared to males ( 1).Ĭancers with sex disparity in incidence and mortality rates. Higher cancer incidences in females are found for breast, thyroid, cranial nerves, and a few of digestive system sites including gallbladder, anus, anal canal, and anorectum. For cancer sites with higher incidence in males, the age-adjusted male-to-female incidence rate ratios range from 1.036 to 9.751, with a median of 1.588. In general, males have a higher incidence and a higher mortality rate than females for most cancer sites, including bladder, kidney, colorectum, liver, esophagus, head and neck, brain, skin, and blood ( 1). ![]() These sex disparities are apparent across a range of non-reproductive cancers and vary by age and race. The mortality rate of all cancer sites combined is 214 for males, and 149 for females per 100,000, age-adjusted 2000–2017 average according to the Surveillance, Epidemiology, and End Results (SEER) program explorer. Sex disparities occur in cancer incidence and mortality ( Figure 1). Better understanding these complex factors and their interactions will improve cancer prevention, treatment, and outcomes for all individuals. In particular, we will explore some of the emerging analytical approaches, such as the use of network methods, that are providing a deeper understanding of the drivers of differences based on sex and gender. In this review, we summarize the current state of knowledge about sex-specific genetic and genome-wide influences in cancer, describe how differences in response to environmental exposures and genetic and epigenetic alterations alter the trajectory of the disease, and provide insights into the importance of integrative analyses in understanding the interplay of sex and genomics in cancer. Extensive sex differences occur genome-wide, and ultimately influence cancer biology and outcomes. Sex differences in cancer may arise due to a combination of environmental, genetic, and epigenetic factors, as well as differences in gene regulation, and expression. ![]() The mandate by the National Institutes of Health that research studies include sex as a biological variable has begun to expand our understanding on its importance. In particular, the molecular mechanisms driving sex differences are poorly understood and so most approaches to precision medicine use mutational or other genomic data to assign therapy without considering how the sex of the individual might influence therapeutic efficacy. Despite their known importance in clinical medicine, differences based on sex and gender are among the least studied factors affecting cancer susceptibility, progression, survival, and therapeutic response.
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