Lack of evidence that proline homozygosity at codon 72 of p53 and rare arginine allele at codon 31 of p21, jointly mediate cervical cancer susceptibility among Indian women.
OBJECTIVE
The objective of this study was to identify whether variants of p53Arg72Pro and p21Ser31Arg were associated with increased risk for cervical cancer (CaCx), either independently or jointly, among Indian women.


METHODS
Genotyping was done by PCR-RFLP using DNA from (i) 120 cervical biopsy tissues of squamous cell carcinoma of the cervix (of which 82 were HPV16/18 positive), and (ii) a total of 205 cytologically normal cervical scrapes (121 HPV-negative and 84 HPV16/18-positive samples, considered as discreet groups). Multiple logistic regression analyses were performed to examine additive or interactive effects of the two factors and for determining age-adjusted OR (95% CI) and P values.


RESULTS
The observed association of proline homozygosity at codon 72 of p53 with CaCx infection (Bhattacharya, P., Duttagupta, C., Sengupta, S. 2002.Proline homozygosity in codon 72 of p53: A risk genotype for Human Papillomavirus related cervical cancer in Indian women. Cancer Lett 188: 207-211) was retained among Indian women harboring HPV16/18 (OR(age-adjusted) = 3.76; 95% CI = 1.03-13.80; P = 0.04). Significant independent association was evident between the p21 arginine allele (rare allele with frequency of 0.1) at codon 31 and CaCx, compared to HPV-negative cytologically normal controls (OR(age-adjusted) = 2.01; 95% CI = 1.00-4.06; P = 0.05). The two risk factors jointly failed to show statistical interaction towards susceptibility to CaCx. The p21 arginine allele was significantly associated with CaCx in the p53 proline non-homozygous group of subjects (OR(age-adjusted) = 2.68; 95% CI: 1.21-5.91; P = 0.01), and specifically in the p53 heterozygous group (OR(age-adjusted) = 2.91; 95% CI = 1.12-7.56; P = 0.03).


CONCLUSIONS
p53 and p21 act in series in mediating cell cycle arrest. However, the two risk factors, p53 proline homozygosity and p21 arginine allele, although part of a common causal pathway, appear to act in a mutually exclusive manner.
Bhattacharya
Paramita
P
Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata 700 108, India.
Sengupta
Sharmila
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001120:Arginine / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D003062:Codon / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007194:India; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011392:Proline / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D003062:Codon; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004273:DNA, Neoplasm; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53; D001120:Arginine; D011392:Proline