Dataset Information

The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network.

ABSTRACT: BACKGROUND:The link between modifiable breast cancer risk factors and tumor genomic alterations remains largely unexplored. We evaluated the association of prediagnostic body mass index (BMI), cigarette smoking, and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30), and nine driver mutations (CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK3CA, RUNX1, and TP53) in a subset of The Cancer Genome Atlas (TCGA). METHODS:Clinical and genomic data were retrieved from the TCGA database. Risk factor information was collected from four TCGA sites (n = 219 women), including BMI (1 year before diagnosis), cigarette smoking (smokers/nonsmokers), and alcohol consumption (current drinkers/nondrinkers). Multivariable regression analyses were conducted in all tumors and stratified according to estrogen receptor (ER) status. RESULTS:Increasing BMI was associated with increasing SCNV in all women (P = 0.039) and among women with ER- tumors (P = 0.031). Smokers had higher SCNV and TSMB versus nonsmokers (P < 0.05 all women). Alcohol drinkers had higher SCNV versus nondrinkers (P < 0.05 all women and among women with ER+ tumors). SBS3 (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER- disease. GATA3 mutation was more likely to occur in women with higher BMI. No association was significant after multiple testing correction. CONCLUSIONS:This study provides preliminary evidence that BMI, cigarette smoking, and alcohol consumption can influence breast tumor biology, in particular, DNA alterations. IMPACT:This study demonstrates a link between modifiable breast cancer risk factors and tumor genomic alterations.

SUBMITTER: Heng YJ

PROVIDER: S-EPMC7060119 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network.

Heng Yujing J YJ Hankinson Susan E SE Wang Jun J Alexandrov Ludmil B LB Ambrosone Christine B CB de Andrade Victor P VP Brufsky Adam M AM Couch Fergus J FJ King Tari A TA Modugno Francesmary F Vachon Celine M CM Eliassen A Heather AH Tamimi Rulla M RM Kraft Peter P

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20200113 3

<h4>Background</h4>The link between modifiable breast cancer risk factors and tumor genomic alterations remains largely unexplored. We evaluated the association of prediagnostic body mass index (BMI), cigarette smoking, and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30), and nine driver mutations (<i>CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK ...[more]

PMID: 31932411

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Project description:BackgroundTo assess metastatic breast cancer (MBC) patient psychological factors, perceptions, and comprehension of tumor genomic testing.MethodsIn a prospective, single institution, single-arm trial, patients with MBC underwent next-generation sequencing at study entry with sequencing results released at progression. Patients who completed surveys before undergoing sequencing were included in the present secondary analysis (n = 58). We administered four validated psychosocial measures: Center for Epidemiologic Studies Depression Scale, Beck Anxiety Inventory, Trust in Physician Scale, and Communication and Attitudinal Self-Efficacy scale for Cancer. Genetic comprehension was assessed using 7-question objective and 6-question subjective measures. Longitudinal data were assessed (n = 40) using paired Wilcoxon signed rank and McNemar's test of agreement.ResultsThere were no significant differences between the beginning and end of study in depression, anxiety, physician trust, or self-efficacy (median time on study: 7.6 months). Depression and anxiety were positively associated with each other and both negatively associated with self-efficacy. Self-efficacy decreased from pre- to post-genomic testing (p = 0.05). Objective genetics comprehension did not significantly change from pre- to post-genomic testing, but patients expressed increased confidence in their ability to teach others about genetics (p = 0.04). Objective comprehension was significantly lower in non-white patients (p = 0.02) and patients with lower income (p = 0.04).ConclusionsThis is the only study, to our knowledge, to longitudinally evaluate multiple psychological metrics in MBC as patients undergo tumor genomic testing. Overall, psychological dimensions remained stable over the duration of tumor genomic testing. Among patients with MBC, depression and anxiety metrics were negatively correlated with patient self-efficacy. Patients undergoing somatic genomic testing had limited genomic knowledge, which varied by demographic groups and may warrant additional educational intervention.Clinical trial informationNCT01987726, registered November 13, 2013.

Dataset Information

The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network.

Publications

The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network.

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