Abstract
BackgroundWhile a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women.MethodsA case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted. Genotyping using the iPLEX GOLD assay was done for 56 haplotype-tagging single nucleotide polymorphisms (SNPs) in 36 breast cancer related genes. Testing for association was done using an additive genetic model. Odds ratios and 95% confidence intervals were calculated using adjusted logistic regression models.ResultsFour SNPs [rs3218550 (XRCC2), rs6917 (PHB), rs1801516 (ATM), and rs13689 (CDH1)] were significantly associated with risk of breast cancer. The rs3218550 T allele and rs6917 A allele increased breast cancer risk by 1.5-fold and 1.4-fold, respectively. The CTC haplotype defined by the SNPs rs3218552|rs3218550|rs3218536 on chromosome 7 (P = 0.0088) and the CA haplotype defined by the SNPs rs1049620|rs6917 on chromosome 17 (P = 0.0067) were significantly associated with increased risk of breast cancer. The rs1801516 A allele and the rs13689 C allele decreased breast cancer risk by 0.6-fold and 0.7-fold, respectively.ConclusionsThese findings suggest that common genetic polymorphisms in the XRCC2, PHB, CDH1 and ATM genes are associated with risk of breast cancer among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast cancer risk need further evaluation using functional studies.
Highlights
While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations
It is hypothesized that a multitude of low-tomoderate penetrance or modifier genetic alleles that are polymorphic in the population, each conferring a small increase in the overall risk, and various environmental factors may contribute to the underlying risk for sporadic breast cancer [4]
single nucleotide polymorphisms (SNPs) rs3218552|rs3218550|rs3218536 on the X-ray repair cross-complementing gene-2 (XRCC2) gene on chromosome 7 (P = 0.008762) and the CA haplotype defined by the SNPs rs1049620|rs6917 on the Prohibitin-1 gene (PHB) gene on chromosome 17 (P = 0.006718) were significantly associated with increased risk of breast cancer (Table 3)
Summary
While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Breast cancer is a multifactorial disease that results from the association between various genetic, environmental, hormonal and lifestyle factors [1]. It is hypothesized that a multitude of low-tomoderate penetrance or modifier genetic alleles that are polymorphic in the population, each conferring a small increase in the overall risk (ranging from just over 1.0 to 2.0 fold), and various environmental factors may contribute to the underlying risk for sporadic breast cancer [4].
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