Sex Disparities in Cancer Mortality and Survival

<div>Abstract<p><b>Background:</b> Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.</p><p><b>Methods:</b> We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.</p><p><b>Results:</b> For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs [e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83)].</p><p><b>Conclusions:</b> Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.</p><p><b>Impact:</b> Future analytic studies should attempt to understand causes of observed sex disparities in cancer. <i>Cancer Epidemiol Biomarkers Prev; 20(8); 1629–37. ©2011 AACR</i>.</p></div>

<div>Abstract<p><b>Background:</b> Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.</p><p><b>Methods:</b> We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.</p><p><b>Results:</b> For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs [e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83)].</p><p><b>Conclusions:</b> Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.</p><p><b>Impact:</b> Future analytic studies should attempt to understand causes of observed sex disparities in cancer. <i>Cancer Epidemiol Biomarkers Prev; 20(8); 1629–37. ©2011 AACR</i>.</p></div>

Eliminating disparities in endometrial cancer: adherence to high-quality care is not enough

INTRODUCTION: Previous research has noted that cancer mortality rates are higher for males than females, but no extensive analysis of this has been conducted. We wanted to study the extent of sex disparities in cancer mortality and if these disparities persist after adjustment for characteristics of the person and cancer. METHODS: We extracted U.S. vital statistics mortality data and cancer incidence and survival data from the SEER*Stat system for 36 cancers and undertook age-adjusted mortality rates and survival analyses. For the age-adjusted mortality rate analyses we extracted mortality count, person-years, and mortality rate per 100,000 for each cancer, stratified by sex and age for the period 1977-2006. Male-to-female mortality rate ratios (MRRs) were calculated. For each cancer, we plotted sex-specific mortality rates and male-to-female MRRs. For the survival analyses, we extracted patient id, age and date of diagnosis, sex, primary site, stage, grade, survival time, vital status and cause of death. Relative hazards for the 5-year period following diagnosis were estimated from Cox proportional hazard models adjusted for age, stage, grade, and year of diagnosis. RESULTS: For the vast majority of cancers, age-adjusted mortality rates were higher among males than females; the 5 cancers with the highest male-to-female MRR were lip (5.51, 95% confidence interval (CI):5.05-6.03), larynx (5.37, 95%CI:5.29-5.45), hypopharynx (4.47, 95%CI:4.30-4.65), esophagus (4.08, 95%CI:4.05-4.11) and urinary bladder (3.36, 95%CI:3.34-3.39). Only 3 cancers had a higher mortality rate among females than males: peritoneum, omentum and mesentery (MRR=0.39, 95%CI:0.38-0.41); gallbladder (0.56, 95%CI:0.55-0.57); and anus, anal canal and anorectum (0.78, 95%CI:0.75-0.81). The survival analyses indicated that males had a significantly increased risk of death, relative to females, for the cancers: anus, anal canal and anorectum (hazard ratio: 1.21, 95%CI:1.03-1.44); colon and rectum (1.08, 95%CI:1.07-1.09); floor of mouth (1.29, 95%CI:1.04-1.59); larynx (1.09, 95%CI:1.01-1.18); liver and intrahepatic bile duct (1.20, 95%CI:1.14-1.26); lung and bronchus (1.19, 95%CI:1.17-1.20); pancreas (1.06, 95%CI:1.03-1.08); small intestine (1.16, 95%CI:1.04-1.29); and soft tissue including heart (1.12, 95%CI:1.03-1.21). Females had higher mortality risks for the cancers tongue (0.87, 95%CI:0.81-0.94) and urinary bladder (0.83, 95%CI:0.81-0.86). DISCUSSION: Male cancer mortality rates were higher than equivalent female rates for the majority of cancers studied. Moreover, males also had higher risk of cancer mortality following diagnosis, relative to females, for many cancers even after adjustment for age of diagnosis, stage, grade and year of diagnosis. These observations indicate that there are sex differences in exposure and/or endogenous metabolic processes which modify risk of both cancer incidence and cancer mortality following diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1834.

PurposeTo inform prevention efforts, we sought to determine which cancer types contribute the most to cancer mortality disparities by individual-level education using national death certificate data for 2017.MethodsInformation on all US deaths occurring in 2017 among 25–84-year-olds was ascertained from national death certificate data, which include cause of death and educational attainment. Education was classified as high school or less (≤ 12 years), some college or diploma (13–15 years), and Bachelor's degree or higher (≥ 16 years). Cancer mortality rate differences (RD) were calculated by subtracting age-adjusted mortality rates (AMR) among those with ≥ 16 years of education from AMR among those with ≤ 12 years.ResultsThe cancer mortality rate difference between those with a Bachelor's degree or more vs. high school or less education was 72 deaths per 100,000 person-years. Lung cancer deaths account for over half (53%) of the RD for cancer mortality by education in the US.ConclusionEfforts to reduce smoking, particularly among persons with less education, would contribute substantially to reducing educational disparities in lung cancer and overall cancer mortality.

This study assessed sex disparities in the causes of death (CODs), both related to cancer and non-cancer, in a nationwide database of cancer survivors in South Korea. Our database included cancer cases diagnosed in Korea between 2009 and 2016, and their CODs up to 2021. Deaths were classified into three categories: index-cancer, non-index-cancer, and non-cancer causes. Male-to-female age-standardized mortality ratios (M/F SMRs) were computed by dividing the male-specific mortality rate by the corresponding female-specific rate. Out of a total of 279,104 (49.0%) recorded deaths in male survivors and 141,674 (27.9%) deaths in female survivors, the M/F SMRs showed an elevated mortality risk in males, both for cancer-related causes (1.46, 95% CI 1.45-1.47) and non-cancer CODs (1.75, 95% CI 1.74-1.77). Among non-cancer CODs, the most significant sex disparity in mortality risk was evident in deaths attributed to chronic lower respiratory diseases (CLRDs), with an SMR of 4.51 (95% CI 4.30-4.73), followed by mortalities due to intentional self-harm (suicide) (2.95, 95% CI 2.85-3.05) and transportation accidents (SMR 2.86, 95% CI 2.67-3.04). Subgroup analysis focusing on survivors of common cancer sites indicated a relatively consistent pattern in index cancer deaths, but the M/F SMRs for non-index cancer and non-cancer deaths demonstrated variability across different cancer sites. Our study underscores an overall elevated mortality risk in male cancer survivors compared to female counterparts. Although deaths stemming from primary cancer remain a substantial concern for both sexes, disparities in non-cancer deaths warrant considerable attention, particularly in relation to CLRD and intentional self-harm (suicide) among male survivors.

ObjectivesTo identify patterns of age disparities in cancer survival, using colon and lung cancer as exemplars.DesignSystematic review of the literature.Data sourcesWe searched Embase, MEDLINE, Scopus and Web of Science through...

Social determinants of sex disparities in cancer in Southeast Asia

Purpose Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying causes are not well understood. We quantified the contribution of tumor, treatment, hospital, sociodemographic, and neighborhood factors to racial/ethnic survival disparities in California. Materials and Methods California Cancer Registry data were used to estimate population-based cancer-specific survival for patients diagnosed with breast, prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic whites. The percentage contribution of factors to overall racial/ethnic survival disparities was estimated from a sequence of multivariable Cox proportional hazards models. Results In baseline models, black patients had the lowest survival for all cancer sites, and Asian American and Pacific Islander patients had the highest, compared with whites. Mediation analyses suggested that stage at diagnosis had the greatest influence on overall racial/ethnic survival disparities accounting for 24% of disparities in breast cancer, 24% in prostate cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status was an important factor in all cancers, but only for black and Hispanic patients. The influence of marital status on racial/ethnic disparities was stronger in men than in women. Adjustment for all covariables explained approximately half of the overall survival disparities in breast, prostate, and colorectal cancer, but it explained only 15% to 40% of disparities in lung cancer. Conclusion Overall reductions in racial/ethnic survival disparities were driven largely by reductions for black compared with white patients. Stage at diagnosis had the largest effect on racial/ethnic survival disparities, but earlier detection would not entirely eliminate them. The influences of neighborhood socioeconomic status and marital status suggest that social determinants, support mechanisms, and access to health care are important contributing factors.

In 2021, the American Cancer Society published its first biennial report on the status of cancer disparities in the United States. In this second report, the authors provide updated data on racial, ethnic, socioeconomic (educational attainment as a marker), and geographic (metropolitan status) disparities in cancer occurrence and outcomes and contributing factors to these disparities in the country. The authors also review programs that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. There are substantial variations in risk factors, stage at diagnosis, receipt of care, survival, and mortality for many cancers by race/ethnicity, educational attainment, and metropolitan status. During 2016 through 2020, Black and American Indian/Alaska Native people continued to bear a disproportionately higher burden of cancer deaths, both overall and from major cancers. By educational attainment, overall cancer mortality rates were about 1.6-2.8 times higher in individuals with ≤12years of education than in those with ≥16years of education among Black and White men and women. These disparities by educational attainment within each race were considerably larger than the Black-White disparities in overall cancer mortality within each educational attainment, ranging from 1.03 to 1.5 times higher among Black people, suggesting a major role for socioeconomic status disparities in racial disparities in cancer mortality given the disproportionally larger representation of Black people in lower socioeconomic status groups. Of note, the largest Black-White disparities in overall cancer mortality were among those who had ≥16years of education. By area of residence, mortality from all cancer and from leading causes of cancer death were substantially higher in nonmetropolitan areas than in large metropolitan areas. For colorectal cancer, for example, mortality rates in nonmetropolitan areas versus large metropolitan areas were 23% higher among males and 21% higher among females. By age group, the racial and geographic disparities in cancer mortality were greater among individuals younger than 65years than among those aged 65years and older. Many of the observed racial, socioeconomic, and geographic disparities in cancer mortality align with disparities in exposure to risk factors and access to cancer prevention, early detection, and treatment, which are largely rooted in fundamental inequities in social determinants of health. Equitable policies at all levels of government, broad interdisciplinary engagement to address these inequities, and equitable implementation of evidence-based interventions, such as increasing health insurance coverage, are needed to reduce cancer disparities.

172 Background: Structural racism (SR) refers to interactive systems of discrimination that perpetuate advantage for one racial group over others. Single-variable SR measures, such as residential segregation and historical red-lining, are associated with cancer disparities but do not represent all aspects of SR. We aimed to develop a composite measure of SR for cancer research and examine the association of county-level SR with disparities in cancer mortality. Methods: Adapting methods from obesity and public safety research, we developed a SR composite score (SRCS) by calculating the ratio of Black to White performance on eight county-level variables across five domains (housing, education, employment, income and healthcare) using race-stratified census data from 2006-2020. Using North Carolina as a test set, we rank-ordered counties on a min-max scale 1-100 for each domain and averaged scores across domains to create the SRCS, where higher SRCS suggests greater SR. Outcomes were county age-standardized mortality rates (per 100k) for all cancers combined, breast, prostate, colorectal and lung cancers, extracted from CDC Wonder for non-Hispanic Blacks and Whites (2000-2020). We used generalized estimating equations to regress mortality rates on SRCS, race, and their interaction. Results: County-level SRCS was positively associated with county-level racial disparities in all-cancer mortality; for each 10-unit increase in SRCS, Black-White difference in rates increased by 15.3/100k (p<0.001). For individual cancers, a 10 unit rise in county SRCS was associated with a 1.93/100k increase in the colorectal cancer mortality gap (p=0.003) and a 6.18/100k increase in the lung cancer mortality gap (p<0.001). SRCS was not associated with mortality disparities for breast and prostate cancers, although these disparities were large. For all-cancer mortality and all tumor types except breast cancer, mortality rates of Whites significantly decreased as SRCS increased, while mortality rates for Blacks remained roughly stable with rising SRCS. Adjustment for county-level measures of social deprivation, unemployment, primary care provider ratio, and severe housing problems did not attenuate the relationship of SRCS with mortality. Conclusions: A composite measure of SR is associated with racial disparities in overall cancer mortality and mortality of specific solid tumors. Continued research is needed to further understand the role of area-level social determinants, ecologic fallacy, and differences in the relationship of SRCS to mortality across cancers. Nevertheless, increased SR is associated with lower county-level cancer mortality among Whites, suggesting that SR may perpetuate cancer mortality disparities via relative advantage to White residents rather than direct disadvantage to Black residents.

Racial disparities in cancer care: can we close the gap?

Introduction: Though cancer mortality rates have declined in recent years, black women still have 40% higher breast cancer mortality rates than whites. In addition, black women and are more likely to be diagnosed with breast cancer before age 45 and to be diagnosed with later stage and more aggressive tumors. The purpose of this study was to examine mortality trends among black and white women younger than 50, comparing trends in racial disparities in breast cancer mortality to trends in mortality from other common cancers and cardiovascular disease (CVD). Methods: The CDC's Mortality Multiple Cause of Death Files were used to obtain cause specific death counts among women aged 20-49 years from 1979-2010. This data file includes information from US death certificates reported to the National Center for Health Statistics. Cause-specific mortality rates were calculated using underlying cause of death counts and U.S. Census intercensal population estimates for each year. Mortality rates were age standardized to the 2000 Standard Population using the direct method. ICD-9 and ICD-10 codes for cancer, CVD, breast cancer, cervical cancer, colorectal cancer, lung cancer, ischemic heart disease, and cerebrovascular disease (stroke) were reconciled using CDC guidelines. Since Hispanic ethnicity was not a required field on death certificates until 1989, race/ethnicity was categorized as black or white prior to 1989, and non-Hispanic white or non-Hispanic black for 1989 onward. Mortality rate-ratios were calculated comparing age-standardized mortality rates for blacks to those of whites. Results: Though mortality rates from both cancer and CVD declined from 1979-2010, black women aged 20-49 had significantly higher mortality rates than whites. In 2010, the cancer mortality rate was 40.6 per 100,000 among blacks compared to 28.8 per 100,000 among whites and the CVD mortality rate was 42.7 per 100,000 among blacks compared to 16.6 per 100,000 among whites. For CVD, the mortality rate-ratio comparing blacks to whites declined from a peak of 4.01 in 1989 to 2.57 in 2010. In contrast, the mortality rate-ratio was more stable for cancer, with a peak mortality rate-ratio of 1.58 in 1998 compared to 1.41 in 2010. Black women had higher mortality rates from breast cancer, colorectal cancer, cervical cancer, ischemic heart disease, and stroke compared to white women over the entire study period. Blacks had higher lung cancer mortality than whites through 2008, and similar or lower mortality rates 2009-2010. The mortality rate-ratio decreased over the study period for ischemic heart disease, stroke, cervical cancer and lung cancer. The mortality rate-ratio increased slightly for colorectal cancer through 2000, and declined after 2000. The mortality rate-ratio increased for breast cancer, from 1.36 in 1979 to 2.00 in 2010. Conclusions: Though mortality rates have declined over the past 30 years for women under 50, significant disparities in the two leading causes of death, cancer and CVD, remain. The persistence of disparities across diseases highlights the need to focus on improving health outcomes broadly, in addition to disease centered approaches, in order to prevent premature deaths among young women. The breast cancer mortality rate was two times greater among black women younger than 50 compared to white women, indicating a more profound disparity in younger women than older women. Furthermore, while relative disparities have decreased over time for most of the causes of death examined, the disparity in breast cancer mortality appears to be widening among young women. We plan to further quantify these trends using joinpoint regression to calculate the average percent change in mortality rates over time. Citation Format: Anne Marie McCarthy, Jianing Yang, Katrina Armstrong. Increasing disparities in breast cancer mortality for young black women in the U.S. from 1979-2010. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B84. doi:10.1158/1538-7755.DISP13-B84

Disparities in Cancer Survival between Indigenous and Non-Indigenous Adults in Canada: Results from a Linkage of the Canadian Long Form Census to the Canadian Cancer Registry

A sexual dimorphism at the cellular level has been suggested to play a role in cancer onset and progression. In particular, very recent studies have unraveled striking differences between cells carrying XX or XY chromosomes in terms of response to stressful stimuli, indicating the presence of genetic and epigenetic differences determining sex-specific metabolic or phenotypic traits. Although this field of investigation is still in its infancy, available data suggest a key role of sexual chromosomes in determining cell life or death. In particular, cells carrying XX chromosomes exhibit a higher adaptive potential and survival behavior in response to microenvironmental variations with respect to XY cells. Cells from females also appear to be equipped with more efficient epigenetic machinery than the male counterpart. In particular, the X chromosome contains an unexpected high number of microRNAs (miRs), at present 118, in comparison with only two miRs localized on chromosome Y, and an average of 40–50 on the autosomes. The regulatory power of these small non-coding RNAs is well recognized, as 30–50% of all protein-coding genes are targeted by miRs and their role in cell fate has been well demonstrated. In addition, several further insights, including DNA methylation patterns that are different in males and females, claim for a significant gender disparity in cancer and in the immune system activity against tumors. In this brief paper, we analyze the state of the art of our knowledge on the implication of miRs encoded on sex chromosomes, and their related functional paths, in the regulation of cell homeostasis and depict possible perspectives for the epigenetic research in the field.