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Estrogen-related genes and their contribution to racial differences in breast cancer risk.

ABSTRACT: Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP-HT interactions in women overall within CYP1B1 (rs1800440; p (het) = 0.003) and within CYP17A1 (rs743572; p (het) = 0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP-HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1 in Black women (p value = 0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.

SUBMITTER: Reding KW

PROVIDER: S-EPMC3356164 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Estrogen-related genes and their contribution to racial differences in breast cancer risk.

Reding Kerryn W KW Chen Chu C Lowe Kimberly K Doody David R DR Carlson Christopher S CS Chen Christina T CT Houck John J Weiss Linda K LK Marchbanks Polly A PA Bernstein Leslie L Spirtas Robert R McDonald Jill A JA Strom Brian L BL Burkman Ronald T RT Simon Michael S MS Liff Jonathan M JM Daling Janet R JR Malone Kathleen E KE

Cancer causes & control : CCC 20120315 5

Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assess ...[more]

PMID: 22418777

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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.

Dataset Information

Estrogen-related genes and their contribution to racial differences in breast cancer risk.

Publications

Estrogen-related genes and their contribution to racial differences in breast cancer risk.

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