Polymorphism of p16 and breast cancer risk in a hospital-based Malaysian population
Authors: Rakesh Naidu, Yip Har, Nur Mohd Taib
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

A69 

The p16 is a tumor suppressor protein that plays an important role in cell cycle regulation. Loss of p16 expression was associated with significantly increased tumor cell proliferation and reduced survival. In the present study, we determined whether the p16 C540G polymorphism alters the risk of breast cancer development. The purpose of our study is to determine the genotype and allele frequencies of p16 in breast cancer cases and normal controls, and to evaluate any association between the polymorphism and breast cancer risk in a hospital-based Malaysian population, clinico-pathological parameters such as estrogen receptor (ER) status, nodal metastases and histological grading, and also with cyclin D1 gene amplification. The patients were also stratified by age at diagnosis to determine any association between the polymorphism and breast cancer risk among women younger or older than 50 years old. The p16 polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Peripheral blood samples were collected from 230 breast cancer patients and 200 normal and healthy women who had no history of breast disease or breast cancer. Of the 230 breast cancer patients, fresh tissues were obtained from 63 patients. All the tumors were invasive ductal carcinomas. Cyclin D1 gene amplification was detected in invasive ductal carcinomas using differential polymerase chain reaction method. The distribution of genotype and allele frequencies of p16 polymorphism were not significantly different between the breast cancer cases and normal subjects (P=0.336; P=0.558). The frequencies of GG genotype (2.2%) and G allele (11.7%) were higher in breast cancer cases as compared to the frequencies of GG (0.5%) and G allele (10.3%) observed in normal individuals. However, CG genotype was slightly elevated in normal women (19.5%) than in the cancer cases (19.1%). Women who were homozygous (OR=4.42; 95% CI, 0.50-101.04) or heterozygous (OR=1.00; 95% CI, 0.60-1.66) for G allele, or carriers of G allele genotype (OR=1.08; 95%, 0.66-1.78) or G allele (OR=1.16; 95% CI, 0.74-1.83) were not associated with breast cancer risk. No significant correlation was noted between G allele genotype and breast cancer risk among patients younger than 50 years (OR=1.15; 95% CI, 0.55-2.41) or 50 years and older (OR=1.03; 95% CI, 0.51-2.06) at diagnosis. The G allele genotype was significantly associated with absence of ER and lymph node metastases but independent of histological grading. Of the 63 invasive ductal carcinomas, 36 were genotyped as CC, 24 as CG and 3 as GG. Cyclin D1 was amplified in 13% (8/63) of the invasive ductal carcinomas. No significant association was found between p16 genotypes and cyclin D1 gene amplification. In conclusion, the polymorphic variant of p16 gene may not be a marker for determining patients’ risk of developing breast cancer but it may be associated with tumor aggressiveness. Our data also showed that amplification of cyclin D1 gene may be not be related to p16 polymorphism.