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Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations.

ABSTRACT: Genome-wide association studies (GWAS) have identified common variants associated with breast cancer risk among women of European and Asian ancestries. To assess the generalizability across ethnic/racial populations of a risk score derived from genotyping 12 highly replicated breast cancer GWAS hits, we performed a case-control study (2224 cases and 2827 controls) nested in the Multiethnic Cohort (MEC) study, which was initiated in 1993-1996 and consists of subjects mainly from European-American, African-American, Native Hawaiian, Japanese and Latino populations. When viewed as a summary risk score, the total number of risk alleles carried by women was significantly associated with breast cancer risk overall (OR per allele, 1.09; 95% CI, 1.06-1.12; P=2.0 × 10(-10)) and in all populations except African-Americans, in which no significant association was observed (OR, 1.03; 95% CI, 0.98-1.08). In aggregate, the number of risk alleles is strongly associated with breast cancer risk in all populations studied except African-Americans. These results emphasize the need for large-scale association studies of multiple racial/ethnic groups for discovery and characterization of risk alleles relevant to all populations in the United States.

SUBMITTER: Chen F

PROVIDER: S-EPMC3025800 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations.

Chen Fang F Stram Daniel O DO Le Marchand Loïc L Monroe Kristine R KR Kolonel Laurence N LN Henderson Brian E BE Haiman Christopher A CA

European journal of human genetics : EJHG 20101124 2

Genome-wide association studies (GWAS) have identified common variants associated with breast cancer risk among women of European and Asian ancestries. To assess the generalizability across ethnic/racial populations of a risk score derived from genotyping 12 highly replicated breast cancer GWAS hits, we performed a case-control study (2224 cases and 2827 controls) nested in the Multiethnic Cohort (MEC) study, which was initiated in 1993-1996 and consists of subjects mainly from European-American ...[more]

PMID: 21102626

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Project description:ImportanceRisk factors for breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND) are poorly understood.ObjectiveTo evaluate rates of and risk factors associated with BCRL in a prospective cohort of women treated with ALND.Design, setting, and participantsThis prospective BCRL screening study performed at a tertiary cancer center enrolled women with breast cancer 18 years and older undergoing breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy.ExposuresRisk of BCRL during the first 2 years after ALND and radiotherapy.Main outcomes and measuresPatients were prospectively evaluated with arm volume (perometer) measurements, and BCRL was defined as a relative volume change of 10% or greater from baseline. Cumulative incidence of BCRL was assessed using competing risk analysis. Risk factors for BCRL were assessed on univariate and multivariable analyses.ResultsFrom November 2016 to March 2020, 304 patients were enrolled; 276 had at least 1 longitudinal measurement. Median (IQR) age was 48 (40-57) years; median (IQR) body mass index, calculated as weight in kilograms divided by height in meters squared, was 26.4 (22.5-31.2). Of the 276 patients included in the analysis, 29 (11%) self-identified as Asian, 55 (20%) as Black, 16 (6%) as Hispanic, 166 (60%) as White, and 10 (3%) as unknown race and ethnicity; 70% received neoadjuvant chemotherapy (NAC); 93% received nodal irradiation. The 24-month BCRL rate was 23.8% (95% CI, 17.9%-29.8%), with significant variation by race and ethnicity (24-month rate: 37.2% [Black], 27.7% [Hispanic], 22.5% [Asian], and 19.8% [White]; P = .004). The BCRL rates were also higher among patients receiving NAC vs up-front surgery (24-month rate: 29.3% vs 11.1%; P = .01). On multivariable analysis, Black race and Hispanic ethnicity (compared with White race) (odds ratio [OR], 3.88; 95% CI, 2.14-7.08 and OR, 3.01; 95% CI, 1.10-7.62, respectively; P < .001 for each), receipt of NAC (compared with up-front surgery) (OR, 2.10; 95% CI, 1.16-3.95; P = .01), older age (OR, 1.04; 95% CI, 1.02-1.07 per 1-year increase; P = .001), and a longer follow-up interval (OR, 1.57; 95% CI, 1.30-1.90 per 6-month increase; P < .001) were independently associated with an increased risk of BCRL, while ERBB2-positive subtype was associated with a decreased risk of BCRL (compared with hormone receptor positive/ERBB2 negative): OR, 0.50; 95% CI, 0.23-0.99; P = .04).Conclusion and relevanceIn this cohort study, Black race, Hispanic ethnicity, NAC receipt, older age, and longer follow-up were independently associated with risk of BCRL. Studies are warranted to evaluate the biologic mechanisms behind racial and ethnic disparities in BCRL development and alternatives to NAC to avoid ALND in tumor subtypes unlikely to achieve nodal pathologic complete response.

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.

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Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations.

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Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations.

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