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Investigation of Two Wnt Signalling Pathway Single Nucleotide Polymorphisms in a Breast Cancer-Affected Australian Population

Published online by Cambridge University Press:  21 February 2012

Plamena N. Gabrovska ,
Robert A. Smith ,
Larisa M. Haupt  and
Lyn R. Griffiths
Plamena N. Gabrovska
Affiliation:
Genomics Research Centre, Griffith Health Institute, Griffith University, Australia
Robert A. Smith
Affiliation:
Genomics Research Centre, Griffith Health Institute, Griffith University, Australia
Larisa M. Haupt
Affiliation:
Genomics Research Centre, Griffith Health Institute, Griffith University, Australia
Lyn R. Griffiths*
Affiliation:
Genomics Research Centre, Griffith Health Institute, Griffith University, Australia
*
ADDRESS FOR CORRESPONDENCE: Professor Lyn Griffiths, Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast campus, Parklands Drive, Southport QLD 4222, Australia. E-mail: l.griffiths@griffith.edu.au

Abstract

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In the mammary gland, Wnt signals are strongly implicated in initial development of the mammary rudiments and in the ductal branching and alveolar morphogenesis that occurs during pregnancy. Previously, we identified two Wnt signaling pathway-implicated genes, PPP3CA and MARK4, as having a role in more aggressive and potentially metastatic breast tumors. In this study, we examined two SNPs within PPP3CA and MARK4 in an Australian case-control study population for a potential role in human breast cancers. 182 cases and 180 controls were successfully genotyped for the PPP3CA SNP (rs2850328) and 182 cases and 177 controls were successfully genotyped for the MARK4 SNP (rs2395) using High Resolution Melt (HRM) analysis. Genotypes of randomly selected samples for both SNPs were validated by dye terminator sequencing. Chi-square tests were performed to determine any significant differences in the genotype and allele frequencies between the cases and controls. Chi-square analysis showed no statistically significant difference (ρ > .05) for genotype frequencies between cases and controls for rs2850328 (χ2 = 1.2, p = .5476) or rs2395 (χ2 = .3, p = .8608). Similarly, no statistical difference was observed for allele frequencies for rs2850328 (χ2 = .68, p = .4108) or rs2395 (χ2 = .02, p = .893). Even though an association of the polymorphisms rs2850328 and rs2395 and breast cancer was not detected in our case-control study population, other variants within the PPP3CA and MARK4 genes may still be associated with breast cancer, as both genes are implicated with processes involved in the disease as well as their mutual partaking in the Wnt signaling pathway.

Keywords

PPP3CAMARK4SNPsassociation studiesgenotypingbreast cancer riskhigh resolution melt analysisDye terminator DNA sequencing
Type
Articles
Information
Twin Research and Human Genetics , Volume 14 , Issue 6 , December 2011 , pp. 562 - 567
Copyright
Copyright © Cambridge University Press 2011

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