A comparison of clinico-biological and genetic markers in sporadic breast cancer in different populations

The aim of this thesis is to examine the hypothesis that breast cancer exhibits ethnic differences in incidence, age of presentation and aggressiveness.;Two approaches were used:;Firstly, International data was examined to find if differences in the age of presentation of breast cancer existed between low and high breast cancer incidence populations.;Secondly, selected pathobiological parameters and genetic markers, chosen to act as surrogate markers of tumour behaviour, were examined in breast cancers from Western Region of Saudi Arabia, Leicester Asians and Leicester Europeans.;Analysis of International data showed countries with the lowest incidence of breast cancer to have a significantly lower mean age of onset than countries with the highest incidence. The mean age of onset in the Western Region was less than Leicester Asians and Leicester Europeans. Statistically significant differences in ASIR were found between the study groups that varied with age.;Breast cancers from Western Region and Leicester Asian women, when compared to the Leicester Europeans, were found to have a more aggressive profile of clinicopathological markers, but a less variable and possibly less aggressive nuclear morphometry.;Molecular alterations at the markers studied appeared to be related to age, 16q exhibiting more Loss of Heterozygosity in older groups and p53 in the younger groups. 6q also showed differences in Loss of Heterozygosity with respect of age, but these differences varied between the populations studied.;The results are consistent with a "two disease" model of breast cancer. It is proposed that the low age of onset seen in the Western Region is primarily due to a low incidence of "older type" of breast cancer rather than an absolute excess of "younger type".