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A genome-wide association study of prognosis in breast cancer.

ABSTRACT: BACKGROUND:Traditional clinicopathologic features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information. MATERIALS AND METHODS:We conducted a genome-wide association study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 single-nucleotide polymorphisms for 1,145 postmenopausal women with invasive breast cancer (7,711 person-years at risk) from the Nurses' Health Study scanned in the Cancer Genetic Markers of Susceptibility initiative. We genotyped the 10 most statistically significant loci (most significant single-nucleotide polymorphism located in ARHGAP10; P = 2.28 x 10(-7)) in 4,335 women diagnosed with invasive breast cancer (38,148 years at risk) in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study. RESULTS:None of the loci replicated in the SEARCH study (all P > 0.10). Assuming a minimum of 10 associated loci, the power to detect at least one with a minor allele frequency of 0.2 conferring a relative hazard of 2.0 at genome-wide significance (P = 5 x 10(-8)) was 99%. CONCLUSION:We did not identify any common germline variants associated with breast cancer survival overall. IMPACT:Our data suggest that it is unlikely that there are common germline variants with large effect sizes for breast cancer survival overall (hazard ratio >2). Instead, it is plausible that common variants associated with survival could be specific to tumor subtypes or treatment approaches. New studies, sufficiently powered, are needed to discover new regions associated with survival overall or by subtype or treatment subgroups.

SUBMITTER: Azzato EM

PROVIDER: S-EPMC2852476 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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A genome-wide association study of prognosis in breast cancer.

Azzato Elizabeth M EM Pharoah Paul D P PD Harrington Patricia P Easton Douglas F DF Greenberg David D Caporaso Neil E NE Chanock Stephen J SJ Hoover Robert N RN Thomas Gilles G Hunter David J DJ Kraft Peter P

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100323 4

<h4>Background</h4>Traditional clinicopathologic features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information.<h4>Materials and methods</h4>We conducted a genome-wide association study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 single-nucleotide polymorphisms for 1,145 postmenopausal women with invasive breast cancer (7,711 person-years at ...[more]

PMID: 20332263

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Project description:INTRODUCTION: Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy. METHODS: We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs. RESULTS: We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10(-9), OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group. CONCLUSIONS: Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer patients.

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A genome-wide association study of prognosis in breast cancer.

Publications

A genome-wide association study of prognosis in breast cancer.

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