J Breast Cancer.  2018 Jun;21(2):165-172. 10.4048/jbc.2018.21.2.165.

Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women

• Sirisena N
• Adeyemo A
• Kuruppu AI
• Samaranayake N
• Dissanayake VHW

• KMID: 2413935
• DOI: http://doi.org/10.4048/jbc.2018.21.2.165

Abstract

PURPOSE
Several single nucleotide polymorphisms (SNPs) have been reported to be associated with clinicopathological profiles in sporadic breast cancer based on studies conducted on major population groups. The knowledge of the effects of these common genetic variants in South Asian populations remains limited. The present study aimed to investigate the association between a selected set of SNPs and the clinicopathological profiles in sporadic breast cancer in Sri Lankan women.
METHODS
A total of 350 postmenopausal women with histologically confirmed invasive breast cancer were genotyped for 58 SNPs located in 36 breast cancer related genes. The clinicopathological factors that were investigated included age of onset, tumor histologic grade, and lymph node involvement, as well as estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status. Association testing was performed using logistic regression models adjusted for confounding factors.
RESULTS
Seven SNPs showed significant associations with clinicopathological profiles in breast cancer. The G allele of BRCA1:rs799917 (p=0.047; β [standard error; SE]=−1.069 [0.537]) and the G allele of NQO2:rs17136117 (p=0.040, β [SE]=1.901 [0.923]) were found to be associated with age of onset between 50 and 59 years. The C allele of CDH1:rs13689 (odds ratio [OR], 2.121; p=0.033) was found to be associated with ER-positive breast cancer. The A allele of AKT1:rs1130214 (OR, 2.095; p=0.011) and the C allele of NQO2:rs2071002 (OR, 1.632; p=0.045) were associated with HER2-positive breast cancer. The C allele of BRCA2:rs15869 (OR, 1.600; p=0.041) and the C allele of CCND1:rs7177 (OR, 1.555; p=0.041) were associated with high tumor histologic grade.
CONCLUSION
The common genetic variants identified in the AKT1, BRCA1, BRCA2, CCND1, CDH1, and NQO2 genes could serve as potential clinical and prognostic biomarkers in sporadic breast cancer patients. Further studies are required to validate our current findings in other populations.

Keyword

Alleles; Breast neoplasms; Postmenopause; Prognosis; Single nucleotide polymorphism

MeSH Terms

Age of Onset
Alleles
Asian Continental Ancestry Group
Biomarkers
Breast Neoplasms*
Breast*
Estrogens
Female
Humans
Logistic Models
Lymph Nodes
Polymorphism, Single Nucleotide
Population Groups
Postmenopause
Prognosis
Receptor, Epidermal Growth Factor
Receptors, Progesterone
Biomarkers
Estrogens
Receptor, Epidermal Growth Factor
Receptors, Progesterone

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