Abstract:
Background: While a range of common genetic variants have been shown to be associated
with sporadic breast cancer risk in several Westem studies,little is known about their role in
South Asian populations. This studywas designed to investigate the association between common genetic variants in breast cancer associated genes and the risk ofbreast cancer in a cohort
of Sri lankan postmenopausal women.
Methods: A case-control study rrvolving 350 postmenopausal breast cancer patients and 350
healthy postmenopausal women was conducted. Peripheral blood DNA was genotyped using
the iPLEX @LD assay for 56 haplotype-tagging single nucleotide variants (SNV) in 36 breast
Glncer related genes. Odds ratios andg5o/o confidence intervals were obtained from adjusted
logistic regression models.
Result: Four SNV [rs3218550 (XRCC2), rs69l7 (PHB), rs1801516 (ATM), and rs13689
(CDHI)l were significantly associated with breast cancer risk. The rs3218550 T allele and
rs69l7 A allele increased the risk of breast cancer by l.5-fold and l.4-fold, respectively. The
CTC haplotype defined by rs32185521rs32185501rs3218536 on chromosome 7 (p:0.0088)
and the CAhaplotype definedbyrs1049620lrs69l7 on chromosome 17 (p=A.OOeZ) were srgnificantly associated with increased breast cancer risk The rs1801516 A allele and the rsl3689
C allele decreased breast cancer risk by 407o and 30%, respectively.
Conclusions: These findings suggest that common genetic variants in the XRCC2, PHB,
CDHI and AIM genes, are associated with breast cancer risk among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast
cancer risk needs furrher evaluation using functional studies.
