Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women.
Since it is well established that inactivation of p53 is involved in pathogenesis of breast cancer, it seems to be reasonable to assume that p53 genetic polymorphism at codon 72 (p53Arg72Pro) which affects the function of p53 might have an influence on breast cancer risk. Thus, in the present study, we have studied the association of p53Arg72Pro polymorphism with breast cancer risk. A case-control study was conducted with 191 breast cancer patients and 218 healthy female controls. p53Arg72Pro polymorphism was examined in their association with breast cancer risk after adjustment for the epidemiological risk factors. Relationship between p53Arg72Pro polymorphism and clinicopathological characteristics of breast cancers was also studied. In addition, frequency of somatic p53 mutation was compared according to the genotype of p53Arg72Pro polymorphism. p5372Pro/Pro homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR) = 2.04, P = 0.04) as compared with p5372Arg/Arg homozygotes, whereas such an association was not found between p5372Pro/Pro homozygotes and ER negative breast cancer risk. Subset analysis according to menopausal status showed that p5372Pro/Pro homozygotes were significantly associated with ER positive breast cancer risk in postmenopausal women (adjusted OR = 3.42, P = 0.01) but not in premenopausal women. Frequency of ER positive tumors was significantly (p < 0.01) higher in breast cancer patients with p5372Pro/Pro genotype (82.8%) than those with p5372Arg/Arg genotype (54.5%). Mutational analysis of p53 in tumors showed that p5372Pro/Pro homozygotes had a lower frequency of p53 mutation (3.5%) than p5372Arg/Arg homozygotes (10.5%). It is suggested that p53Arg72Pro polymorphism is associated with ER positive breast cancer risk, especially, in postmenopausal women. The higher frequency of p53 somatic mutation in p5372Arg/Arg homozygotes than p5372Pro/Pro homozygotes is consistent with the thesis that the function of p5372Pro/Pro is impaired so that a further alteration of p53 gene is less required in p5372Pro/Pro homozygotes than p5372Arg/Arg homozygotes.
Noma
Chikako
C
Department of Surgical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka/E10, Yamada-oka, Suita City, Osaka 565 0871, Japan.
Miyoshi
Yasuo
Y
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D000328:Adult; D000368:Aged; D001120:Arginine; D001943:Breast Neoplasms / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008593:Menopause; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011392:Proline; D011960:Receptors, Estrogen / Q000032:analysis*; D012307:Risk Factors
D003062:Codon; D011960:Receptors, Estrogen; D001120:Arginine; D011392:Proline