Dataset Information

The association of single nucleotide polymorphisms (SNPs) with breast density and breast cancer survival: the Malmo Diet and Cancer Study.

ABSTRACT: BACKGROUND:Genetic factors are important in determining breast density, and heritable factors account for 60% of the variation. Certain single nucleotide polymorphisms (SNPs) are associated with density and risk of breast cancer but the association with prognosis is not clear. PURPOSE:To investigate associations between selected SNPs and breast cancer survival in the Malmö Diet and Cancer Study (MDCS). MATERIAL AND METHODS:A total of 724 unrelated women with breast cancer and registered radiological and pathological data were identified in MDCS 1991-2007, with genotyping available for 672 women. Associations among 15 SNPs, density, and breast cancer-specific survival were analyzed using logistic/Cox regression, adjusted for factors affecting density and survival. Variants significantly associated with either density or survival were validated in a large independent breast cancer cohort (LIBRO-1). RESULTS:Minor homozygotes of SNPs rs9383589, CCDC170 and rs6557161, ESR1 were associated with high breast density (adjusted odds ratio [AOR] 8.97, 95% confidence interval [CI] 1.35-59.57; AOR 2.08, 95% CI 1.19-3.65, respectively) and poorer breast cancer survival (adjusted hazard ratio [HRadj] 6.46, 95% CI 1.95-21.39; HRadj 2.30, 95% CI 1.33-3.96, respectively) compared to major homozygotes. For SNP rs3757318, ESR1, minor homozygotes (HRadj 7.46, 95% CI 2.28-24.45) were associated with poorer survival. We confirmed that rs6557161, ESR1 was significantly associated with both density and survival in the LIBRO-1 study. CONCLUSION:These findings support a shared genetic basis for density and breast cancer survival. The SNP significantly associated with both density and survival in both cohorts may be of interest in future research investigating polygenic risk scores for breast cancer risk and screening stratification purposes.

SUBMITTER: Sartor H

PROVIDER: S-EPMC7564305 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The association of single nucleotide polymorphisms (SNPs) with breast density and breast cancer survival: the Malmö Diet and Cancer Study.

Sartor Hanna H Brandt Jasmine J Grassmann Felix F Eriksson Mikael M Czene Kamila K Melander Olle O Zackrisson Sophia S

Acta radiologica (Stockholm, Sweden : 1987) 20200209 10

<h4>Background</h4>Genetic factors are important in determining breast density, and heritable factors account for 60% of the variation. Certain single nucleotide polymorphisms (SNPs) are associated with density and risk of breast cancer but the association with prognosis is not clear.<h4>Purpose</h4>To investigate associations between selected SNPs and breast cancer survival in the Malmö Diet and Cancer Study (MDCS).<h4>Material and methods</h4>A total of 724 unrelated women with breast cancer a ...[more]

PMID: 32036684

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Project description:Importance:Single-nucleotide polymorphisms (SNPs) have demonstrated an association with breast cancer susceptibility, but there is limited evidence on how to incorporate them into current breast cancer risk prediction models. Objective:To determine whether a panel of 18 SNPs (SNP18) may be used to predict breast cancer in combination with classic risk factors and mammographic density. Design, Setting, and Participants:This cohort study enrolled a subcohort of 9363 women, aged 46 to 73 years, without a previous breast cancer diagnosis from the larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at Screening) specifically to evaluate breast cancer risk-assessment methods. Enrollment took place from October 2009 through June 2015 from multiple population-based screening centers in Greater Manchester, England. Follow-up continued through January 5, 2017. Exposures:Genotyping of 18 SNPs, visual-assessment percentage mammographic density, and classic risk assessed by the Tyrer-Cuzick risk model from a self-completed questionnaire at cohort entry. Main Outcomes and Measures:The predictive ability of SNP18 for breast cancer diagnosis (invasive and ductal carcinoma in situ) was assessed using logistic regression odds ratios per interquartile range of the predicted risk. Results:A total of 9363 women were enrolled in this study (mean [range] age, 59 [46-73] years). Of these, 466 were found to have breast cancer (271 prevalent; 195 incident). SNP18 was similarly predictive when unadjusted or adjusted for mammographic density and classic factors (odds ratios per interquartile range, respectively, 1.56; 95% CI, 1.38-1.77 and 1.53; 95% CI, 1.35-1.74), with observed risks being very close to expected (adjusted observed-to-expected odds ratio, 0.98; 95% CI, 0.69-1.28). A combined risk assessment indicated 18% of the subcohort to be at 5% or greater 10-year risk, compared with 30% of all cancers, 35% of interval-detected cancers, and 42% of stage 2+ cancers. In contrast, 33% of the subcohort were at less than 2% risk but accounted for only 18%, 17%, and 15% of the total, interval, and stage 2+ breast cancers, respectively. Conclusions and Relevance:SNP18 added substantial information to risk assessment based on the Tyrer-Cuzick model and mammographic density. A combined risk is likely to aid risk-stratified screening and prevention strategies.

Project description:BACKGROUND:Breast density and single-nucleotide polymorphisms (SNPs) have both been associated with breast cancer risk. To determine the extent to which these two breast cancer risk factors are associated, we investigate the association between a panel of validated SNPs related to breast cancer and quantitative measures of mammographic density in a cohort of Caucasian and African-American women. METHODS:In this IRB-approved, HIPAA-compliant study, we analyzed a screening population of 639 women (250 African American and 389 Caucasian) who were tested with a validated panel assay of 12 SNPs previously associated to breast cancer risk. Each woman underwent digital mammography as part of routine screening and all were interpreted as negative. Both absolute and percent estimates of area and volumetric density were quantified on a per-woman basis using validated software. Associations between the number of risk alleles in each SNP and the density measures were assessed through a race-stratified linear regression analysis, adjusted for age, BMI, and Gail lifetime risk. RESULTS:The majority of SNPs were not found to be associated with any measure of breast density. SNP rs3817198 (in LSP1) was significantly associated with both absolute area (p?=?0.004) and volumetric (p?=?0.019) breast density in Caucasian women. In African-American women, SNPs rs3803662 (in TNRC9/TOX3) and rs4973768 (in NEK10) were significantly associated with absolute (p?=?0.042) and percent (p?=?0.028) volume density respectively. CONCLUSIONS:The majority of SNPs investigated in our study were not found to be significantly associated with breast density, even when accounting for age, BMI, and Gail risk, suggesting that these two different risk factors contain potentially independent information regarding a woman's risk to develop breast cancer. Additionally, the few statistically significant associations between breast density and SNPs were different for Caucasian versus African American women. Larger prospective studies are warranted to validate our findings and determine potential implications for breast cancer risk assessment.

Dataset Information

The association of single nucleotide polymorphisms (SNPs) with breast density and breast cancer survival: the Malmo Diet and Cancer Study.

Publications

The association of single nucleotide polymorphisms (SNPs) with breast density and breast cancer survival: the Malmö Diet and Cancer Study.

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