The usefulness of the arginine (Arg) residue at codon 72 of the p53 tumor suppressor gene as a marker for the risk of cervical cancer remains unclear. Studies to date have focused mainly on Caucasian subjects despite marked ethnic variations in both the p53 polymorphism and the frequency of cervical carcinoma. Furthermore, not all studies have taken into account the type of human papillomavirus (HPV) infection present. In this study, undertaken at King Edward VIII Hospital, Durban, South Africa, we determined the p53 codon 72 status in 281 black South African women with cervical cancer and 340 ethnically matched healthy control subjects. In addition, HPV DNA was confirmed in 190 cervical tumors and the viral type determined. Results showed that overall more cancer patients than control subjects had an Arg allele at codon 72 with respect to both genotype and allelotype (P < 0.05). A significantly higher (P < 0.001) Arg allele frequency (55%) was also observed in patients whose tumors contained low or intermediate risk HPV DNA compared with control subjects (31%); the Arg homozygosity rate was 34% and 9% in patients and controls, respectively (P < 0.001). In contrast, patients harboring HPV 16/18 infections showed no differences in p53 status compared with controls. It would appear that, in the absence of HPV 16/18 infections, the Arg allele at codon 72 of the p53 tumor suppressor gene may constitute a risk factor for carcinogenesis of the cervix.
The p53 codon 72 genotype was examined in blood samples taken from 121 Zulu‐speaking black South African women with histologically proven squamous carcinoma of the cervix. Freshly biopsied tumour tissue was also available for human papillomavirus subtyping from 100 of these women. A control group consisted of 251 healthy race‐matched women attending a contraceptive service facility. The results show that there were no statistically significant differences in the frequency of the homozygous arginine genotype between patients with cancer of cervix, irrespective of human papillomavirus status, and healthy controls. This finding suggests that the arginine allele does not predispose towards viral tumour genesis in this population, and supports the findings of research done in other ethnic groups.
The polymorphic C677T mutation in the gene encoding 5,lO methylenetetrahydrofolate reductase has been shown to be a risk factor for pre-eclampsia in Japanese and European women when inherited as a homozygous trait. We attempted to verify these findings in a black African population with a high incidence of pre-eclampsia. No difference in frequency of the T-allele was observed in 105 women with preeclampsia, compared with 110 healthy pregnant normotensive women. Only one woman with pre-eclampsia was TT homozygous, suggesting that methylenetetrahydrofolate reductase polymorphism is not an important factor in the pathogenesis of pre-eclampsia in black South African women.
We examined 232 breast carcinomas for c-erbB-2 amplification by Southern analysis using two different cDNA probes. Using these same probes, 95 of these tumors were also examined for mRNA expression by Northern analysis. Amplification was detected in 20 and 17% of the tumors with the probes pHER 2 and pCER 204, respectively, but only 10% showed amplification with both probes. A significantly higher incidence (p < 0.01) of mRNA overexpression was detected with the pHER 2 probe (34%) compared with the pCER 204 probe (16%), with only 11% of tumors demonstrating overexpression with both probes. A total of 10 tumors (11%) exhibited amplification as well as overexpression with pHER 2, whereas significantly fewer (3%) manifested both abnormalities with the larger pCER 204 probe (p < 0.05). Amplification of c-erbB-2, as detected with the pHER 2 probe but not with the pCER 204 probe, was significantly associated with the absence of both estrogen and progesterone receptors (p < 0.05 and p < 0.01, respectively). No relationship was found with other clinical prognostic indicators, such as nodal involvement and metastases. As determined by either probe, overexpression was not associated with prognostic indicators. There was no significant difference in the c-erbB-2 status of tumors from different racial groups.
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