Sex Differences in Cancer Incidence and Survival: A Pan-Cancer Analysis

Abstract Background: Sex plays an important role in the incidence, prognosis, and mortality of cancers, but often is not considered in disease treatment. Methods: We quantified sex differences in cancer incidence using the United States Cancer Statistics (USCS) public use database and sex differences in cancer survival using Surveillance, Epidemiology, and End Results (SEER) public use data from 2001 to 2016. Age-adjusted male-to-female incidence rate ratios (IRR) with 95% confidence intervals (CI) were generated by primary cancer site, race, and age groups. In addition, age-adjusted hazard ratios with 95% CI by sex within site were generated. Results: In general, cancer incidence and overall survival were lower in males than females, with Kaposi sarcoma (IRR: 9.751; 95% CI, 9.287–10.242; P < 0.001) having highest male-to-female incidence, and thyroid cancers (HR, 1.774; 95% CI, 1.707–1.845) having largest male-to-female survival difference. Asian or Pacific Islanders had particularly high male-to-female incidence in larynx cancers (IRR: 8.199; 95% CI, 7.203–9.363; P < 0.001), relative to other races. Among primary brain tumors, germ cell tumors had the largest male-to-female incidence (IRR: 3.03; 95% CI, 2.798–3.284, P < 0.001). Conclusions: Overall, incidence and survival of cancer vary significantly by sex, with males generally having lower incidence and survival compared with females. Male-to-female incidence differences were also noted across race and age groups. These results provide strong evidence that the fundamental biology of sex differences affects cancers of all types. Impact: This study represents the most recent and comprehensive reporting of sex differences in cancer incidence and survival in the United States. Identifying disadvantaged groups is critical as it can provide useful information to improve cancer survival, as well as to better understand the etiology and pathogenesis of specific cancers.