Case-Control Study On The Associations Of Genetic Polymorphisms Of ER And PR With The Risk Of Breast Cancer

[Background] Over the latest 20 years, the incidence rate of breast cancer has beenincreasing rapidly and the age of patients has become more and more young in China. Ithas become the major malignant tumor threatening the health and life of women. Hence, itis urgent to explore new risk factors for the breast cancer from new perspectives. Somestudies showed that the estrogen, progestin themselves and other estrogen and,progestin-related factors may be associated with breast cancer risk, and the geneticpolymorphisms of ER(estrogen receptor)and PR(progestin receptor) genes were thought tobe the risk factors of breast cancer. Hence, we hypothesized that there might have thegene-gene and gene-environment joint risk effects on breast cancer among thepolymorphisms of ER codon325 and PR +331G/A, and these polymorphisms with someenvironment exposures regarding the estrogen and progestin.[Objective] We are sought to examine whether the 2 genetic polymorphisms(ERcodon325 and PR +331G/A) could increase the breast Cancer risk of Chinese women, andto further estimate gene-gene and gene-environment joint risk effects on the breast cancer.[Method] Breast cancer cases aged from 25～70 years old who were diagnosed duringthe period from Jan 1, 2005 to Jul 1, 2006 came from the First People's Hospital ofChangzhou and Suzhou. Age-frequency matched controls with no history of malignanttumor came from gynecological diseases examination in Changzhou and Suzhou. All studyparticipants were interviewed using standard structured qestionnaires including age, historyof reproduction, contraception, menstruation, history of breast diseases, etc, and asked toprovide 3ml peripheral blood. Totally, 420 subjects, namely 206 cases and 214 controls,entered into final analysis. We performed the real-time PCR assays to determine thesusceptibility of breast cancer from the role of genetic polymorphisms of ER codon325 andPR +331G/A.Quality control measures, such as double data entry and check, repeated measurement using real-time PCR in 10% samples, DNA sequence identification in 10 typical sampleswere used. The statistical methods included chi-square test, Hardy-Weinberg balance test,unconditional logistic regression, and Rothman additive effects test for gene-environments.SAS 8.1 software was used to analyze the data (SAS Institute, Cary, NC USA).[Results] Being younger at menarche, oral contraceptives intake, family history ofbreast cancer, benign breast disease history, passive smoking, pork meat and preservedfoods intakes were significantly associated with an increased risk of breast cancer.Drinking green tea more than 20 years, physical exercises, soybean foods and fresh fruitsintake could decrease the risk of breast cancer. No associations were found between usingsexual hormone, having taken anti-latic excreting medicine, height, body weight, BMI andbreast cancer risk.The frequency of CC, CG and GG for ER codon325 in control women were 25.23%,53.27% and 21.50%, the frequency of GA, GG for PR +331G/A in control women were92.99% and 7.01%.We have not found that the polymorphism of ER codon325 was associated with therisk of breast cancer. Compared with CC genotype, the adjusted OR for the CG and GGwere 0.99(95%CI: 0.61-1.61) and 1.13 (95%CI: 0.62-2.04), respectively. The PR +331G/Apolymorphism probably had the weak associations with breast cancer risk. Compared withGA genotype, the adjusted OR for GG was 1.51(95%CI: 0.74-3.07), which had nostatistically significance.The joint effect between the polymorphisms of ER codon325 and PR +331G/A wasshown to be associated with the breast cancer risk, but with no statistically significance.Compared with the subjects with both CC, CG (ER codon325) and GA (PR +331G/A)genotypes, the adjusted OR for the women carring both CC, CG(ER codon325) andGG(PR +331G/A) was 1.80 (95%CI: 0.76-4.30), the adjusted OR for the women carringboth GG(ER codon325) and GA(PR +331G/A) was 1.19 (95%CI: 0.71-2.01), and theadjusted OR for the women carring both GG(ER codon325) and GG(PR +331G/A) was1.16(955CI: 0.34-3.94). The joint effect between ER codon325 and spontaneous abortion appearedincreasing the risk of breast cancer with statistically marginal significance (OR=3.57,95%CI=1.21-10.52, Rothman additive test, u=1.90, P=0.0588). We did not find that thesignificant additive synergic effects appeared brtween the 2 genetic polymorphisms andother environmental factors.[Conclusion]1. Being younger at menarche and oral contraceptives intake were significantly associatedwith the increased risk of breast cancer. Drinking green tea for years could decrease therisk of breast cancer.2. There was no association between ER codon325 polymorphism and breast cancer risk.3. PR +331G/A polymorphism may be associated with the increasing breast cancer risk,weakly.4. Probably, there was joint effect between ER codon325 and PR +331G/Apolymorphisms to increase the risk of breast cancer.5. The women who are both with history of spontaneous abortion and carry ER codon325CG or GG genotypes might be the susceptive subjects of breast cancer.