Oral Presentation COSA-IPOS Joint Scientific Meeting 2012

A genome-wide association study of vulvar cancer in Aboriginal women resident in Arnhem Land (#24)

Rebekah McWhirter 1 2 , Joanne Dickinson 1 2 , Russell Thomson 2 , James Marthick 2 , Debbie Taylor-Thomson 1 , Matthew Brown 3 , Alice Rumbold 4 , John Condon 1
  1. Menzies School of Health Research, Darwin, NT, Australia
  2. Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
  3. Diamantina Institute, University of Queensland, Brisbane, Australia
  4. Obstetrics and Gynaecology, University of Adelaide, Adelaide, South Australia, Australia

Cancer of the vulvar is fifty times more common in young Aboriginal women in Arnhem Land than in other Australian women.1   Human papillomavirus (HPV) infection is associated with vulvar cancer and its precursor lesions, vulvar intraepithelial neoplasia (VIN), in younger women, yet an earlier stage of this study found that neither an increased incidence of HPV nor a particularly virulent HPV strain could explain the excess incidence of vulvar cancer in this population (publication under review).  This study recruited 30 women diagnosed with vulvar cancer or VIN and whose normal place of residence was in Arnhem Land, and 62 controls matched for age and community of residence.  Saliva samples were collected from all participants for DNA extraction, and genotyped using an Illumina Human Omni2.5 BeadChip.  One control sample showed evidence of contamination, and was excluded (n=91).  After quality control, a total of 940213 autosomal SNPs were included in the analysis.  Initial association analyses identified one significant (p=4.01x10-8) peak on chromosome 10, and two suggestive peaks on chromosomes 21 (p=3.83x10-7) and 17 (p=6.33x10-7).  To control for cryptic relatedness within the sample, results were reanalysed using ROADTRIPS software to adjust for relatedness using genomic estimates of kinship and inbreeding, with peaks on chromosomes 10 (p=5.91x10-7) and 21 (p=3.87x10-6) remaining strongly suggestive.  Taken together with previous work, these results provide strong evidence of a genetic component in the aetiology of vulvar cancer in this population, and form the basis of future sequencing work that will aim to identify the causal variants.

  1. John R. Condon, Alice R. Rumbold, Jane C. Thorn, Margaret M. O’Brien, Margaret J. Davy and Ibrahim Zardawi, (2009) A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian Indigenous women, Cancer Causes and Control, 20(1): 67-74.