Breast and prostate cancer risk are not associated with increased homozygosity in outbred populations

Richard Houlston (1) , Victor Enciso-Mora (1) , Fay J Hosking (1)

1 Section of Cancer Genetics,

Regions of restricted genetic heterogeneity due to identity by descent (autozygosity) are known to confer susceptibility to a number of diseases. Regions of germline homozygosity (ROH) of 1-2Mb, the result of autozygosity, are detectable at high frequency in outbred populations. Recent studies have reported that ROH, possibly through exposing recessive disease-causing alleles or alternative mechanisms, are associated with an increased cancer risk. To examine whether homozygosity is associated with breast or prostate cancer risk we analysed 500K SNP data from two genome-wide association studies conducted by Cancer Genetics Markers of Susceptibility initiatives (http://cgems.cancer.gov/). Six common ROH were associated with breast cancer risk and four with prostate cancer (P<0.01). Intriguingly, one of the breast cancer ROH maps to 6q22.31-6q22.3 a region that has been previously shown to confer breast cancer risk. While none of the ROH remained significantly associated with cancer risk after adjustment for multiple testing, a number of the ROHs merit further interrogation. Our findings do however provide no strong evidence that levels of measured homozygosity, whatever their aetiology (autozygosity, uniparental isodisomy or hemizygosity) confer an increased risk of developing breast or prostate cancer in predominantly outbred populations.

Mots clés: homozygosity; prostate; breast

Richard Houlston, Victor Enciso-Mora, Fay J Hosking. Breast and prostate cancer risk are not associated with increased homozygosity in outbred populations. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.53⟩. ⟨hal-00528086⟩