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Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer.

ABSTRACT: Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health behaviors, etc.) have a strong influence on racial disparities. However, even after controlling for these factors, overall phenotypic differences in breast cancer pathology remain among groups of individuals who vary by geographic ancestry. There is a growing appreciation that chronic/reoccurring inflammation, primarily driven by mechanisms of innate immunity, contributes to core functions associated with cancer progression. Germline mutations in innate immune genes that have been retained in the human genome offer enhanced protection against environmental pathogens, and protective innate immune variants against specific pathogens are enriched among populations whose ancestors were heavily exposed to those pathogens. Consequently, it is predicted that racial/ethnic differences in innate immune programs will translate into ethnic differences in both pro- and antitumor immunity, tumor progression, and prognosis, leading to the current phenomenon of racial/ethnic disparities in cancer. This review explores examples of protective innate immune genetic variants that are (i) distributed disproportionately among racial populations and (ii) associated with racial/ethnic disparities of breast and prostate cancer.

SUBMITTER: Yeyeodu ST

PROVIDER: S-EPMC6730653 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer.

Yeyeodu Susan T ST Kidd LaCreis R LR Kimbro K Sean KS

Cancer immunology research 20190901 9

Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health behaviors, etc.) have a strong influence on racial disparities. However, even after controlling for these factors, overall phenotypic differences in breast cancer pathology remain among ...[more]

PMID: 31481520

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Project description:BackgroundPrior studies suggest that referral to genetic counseling and completion of genetic testing vary by race/ethnicity; however, the data are limited.ObjectiveWe sought to evaluate patterns of genetic testing and clinical outcomes across race/ethnicity at a hereditary breast and ovarian cancer center.DesignThe medical records for all patients undergoing genetic assessment at a hereditary breast and ovarian cancer center were reviewed and stratified by self-reported race/ethnicity (non-Hispanic White, Hispanic, non-Hispanic Black, and Asian).ParticipantsA total of 1666 patients met inclusion criteria (non-Hispanic Whites, 1367; Hispanics, 85, non-Hispanic Blacks, 101; Asians, 113).Main measuresDemographics, patient characteristics, and referral patterns for patients who underwent genetic testing were analyzed using Kruskal-Wallis tests, chi-square test, or Fisher's exact tests, stratifying by self-reported race/ethnicity. Pathogenic mutations and variants of unknown significance (VUS) were reviewed. Outcomes of patients with genetic mutations and personal history of breast and/or gynecologic malignancies were compared.Key resultsNon-Hispanic Whites were more likely to be referred due to family cancer history compared to all other ethnicities while Non-Hispanic Blacks, Hispanics, and Asians were more likely to be referred due to personal history of cancer (p < 0.001). Non-Hispanic Blacks and Hispanics were more likely to have advanced-stage cancer at the time of genetic testing (p < 0.02). Rates of mutations did not differ by race/ethnicity when Ashkenazi Jewish patients were excluded (p = 0.08). Among patients found to have a BRCA1/2 mutation, Non-Hispanic Whites were more likely to undergo cancer screening and risk-reducing surgery compared with all other ethnicities (p = 0.04).ConclusionsMinority patients were more likely to utilize genetic services following a cancer diagnosis and less likely due to family cancer history, suggesting a missed opportunity for mutation detection and cancer prevention in this population. Efforts to eradicate racial/ethnic disparities in early access to genetic testing and guided cancer prevention strategies are essential.

Project description:PurposeTumors of the inner quadrants of the breast are associated with poorer survival than those of the upper-outer quadrant. It is unknown whether racial differences in breast cancer outcomes are modified by breast quadrant, in addition to comparisons among Asian subgroups.MethodsUsing the Surveillance, Epidemiology, and End Results database, we analyzed data among women diagnosed with non-metastatic invasive breast cancer between 1990 and 2014. We performed Cox proportional hazards regression models to assess the associations of race with breast cancer-specific survival and overall survival, stratified by breast quadrants. The models were adjusted for age, year of the diagnosis, tumor size, grade, histological type, tumor laterality, lymph node, estrogen receptor, progesterone receptor, and treatments.ResultsAmong 454,154 patients (73.0% White, 10.0% Black, 7.8% Asian/PI, and 9.2% Hispanic), 54.3% had tumors diagnosed in the upper-outer quadrant of the breast. Asian/PI women were more likely than White to have tumors diagnosed in the nipple/central portion of the breast and were less likely to have diagnosed in the upper-outer quadrant (P < 0.001), despite a similar distribution of breast quadrant between Black, Hispanic, and White women. Compared with White women, the multivariable-adjusted hazard ratios of breast cancer-specific mortality were 1.41 (95% CI 1.37-1.44) in Black women, 0.82 (95% CI 0.79-0.85) in Asian women, and 1.05 (95% CI 1.02-1.09) in Hispanic women. Among Asian subgroups, Japanese American women had a lower risk of breast cancer-specific mortality (HR = 0.68, 95% CI 0.62-0.74) compared with White women. Overall survival was similar to breast cancer-specific survival in each race group. The race-associated risks did not vary significantly by breast quadrants for breast cancer-specific mortality and all-cause mortality.ConclusionsDifferences in breast cancer survival by race could not be attributed to tumor locations. Understanding the cultural, biological, and lifestyle factors that vary between White, African American, and ethnic subgroups of Asian American women may help explain these survival differences.

Project description:BackgroundLimited studies have investigated racial/ethnic survival disparities for breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status in a multiethnic population.MethodsUsing multivariable Cox proportional hazards models, we assessed associations of race/ethnicity with ER/PR-specific breast cancer mortality in 10,366 California women diagnosed with breast cancer from 1993 to 2009. We evaluated joint associations of race/ethnicity, health care, sociodemographic, and lifestyle factors with mortality.ResultsAmong women with ER/PR+ breast cancer, breast cancer-specific mortality was similar among Hispanic and Asian American women, but higher among African American women [HR, 1.31; 95% confidence interval (CI), 1.05-1.63] compared with non-Hispanic White (NHW) women. Breast cancer-specific mortality was modified by surgery type, hospital type, education, neighborhood socioeconomic status (SES), smoking history, and alcohol consumption. Among African American women, breast cancer-specific mortality was higher among those treated at nonaccredited hospitals (HR, 1.57; 95% CI, 1.21-2.04) and those from lower SES neighborhoods (HR, 1.48; 95% CI, 1.16-1.88) compared with NHW women without these characteristics. Breast cancer-specific mortality was higher among African American women with at least some college education (HR, 1.42; 95% CI, 1.11-1.82) compared with NHW women with similar education. For ER-/PR- disease, breast cancer-specific mortality did not differ by race/ethnicity and associations of race/ethnicity with breast cancer-specific mortality varied only by neighborhood SES among African American women.ConclusionsRacial/ethnic survival disparities are more striking for ER/PR+ than ER-/PR- breast cancer. Social determinants and lifestyle factors may explain some of the survival disparities for ER/PR+ breast cancer.ImpactAddressing these factors may help reduce the higher mortality of African American women with ER/PR+ breast cancer.

Dataset Information

Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer.

Publications

Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer.

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