OBJECTIVETo explore the application of counter-matching design in epidemiological research.

METHODSThrough elaboration of the study about gene-environment interactions in the etiology of breast cancer, methodology regarding counter-matching design and statistic methods was introduced.

RESULTSThis design improved the potential for detecting gene-environment interactions for diseases when both gene mutations and the environmental exposures of interest were rare in the general population.

CONCLUSIONCounter-matching appearsed to be more appropriate than most traditional epidemiologic methods for the study of interactions involving rare factors.

Breast Neoplasms ; epidemiology ; etiology ; genetics ; radiotherapy ; Epidemiologic Methods ; Humans ; Male

OBJECTIVETo estimate the contribution of known identified risk factors to breast cancer incidence and mortality in China, and provide evidence to support the prevention and control of breast cancer for Chinese females.

METHODSWe calculated the proportion of breast cancer attributable to specific risk factors. Data on exposure prevalence were obtained from Meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were obtained from Meta-analyses and large-scale prospective studies. Cancer mortality and incidence were taken from the Third National Death Survey and from cancer registries in China.

RESULTSThe first 5 risk factors of breast cancer in China were benign breast disease (RR = 2.62), family history of breast cancer (RR = 2.39), smoking (RR = 1.86), overweight (RR = 1.60) and age at menarche (RR = 1.54). The proportion of breast cancer deaths attributable to reproductive factors, lifestyle factors, benign breast disease, the use of external hormone and family history of breast cancer was 27.84%, 23.55%, 15.09%, 3.60% and 2.49%, respectively. The total population attributable fraction (PAF) was 55.95% for risk factors in our study. Overall, we estimated that 79 862 breast cancer cases and 22 456 deaths were attributed to the five risk factors in China in 2005.

CONCLUSIONSThe prevention and control of unhealthy lifestyle factors may significantly reduce the number and death of breast cancer in China.

Breast Diseases ; complications ; Breast Neoplasms ; epidemiology ; etiology ; genetics ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; Humans ; Menarche ; Meta-Analysis as Topic ; Overweight ; complications ; Risk Factors ; Smoking ; adverse effects

It is not yet clear whether Glutathione S-transferase M1 (GSTM1) polymorphisms affect the risk of breast cancer. The aim of this study is to provide a comprehensive meta-analysis of all the available, published case-control studies on the extent of the possible association between GSTM1 polymorphisms and susceptibility to breast cancer. Twenty case-control studies on GSTM1 and breast cancer were identified using both PUBMED and a manual search. Meta-analysis was conducted by the Peto method. Subgroup analyses were undertaken, in order to explore the relationship between effect sizes and the study characteristics. The overall odds ratio (OR) was found to be 1.06 (95% CI, 0.99-1.14). The OR for post-menopausal women with GSTM1 deficiency was determined to be 1.19 (95% CI, 1.05-1.34). In populations with a low frequency of GSTM1 deficiency, a greater increase was observed (OR, 1.20; 95% CI, 1.08-1.34). Furthermore, the highest associations were found in post-menopausal women with a low frequency of GSTM1 deficiency (OR, 1.44; 95% CI, 1.20-1.73). The fact that GSTM1 deficiency is not rare in the general population implies that the attributable risk for breast cancer could be sizable. Further studies focusing on the structure of haplotype blocks of GSTM1 are required in order to find a specific haplotype with a predisposing breast cancer susceptibility allele.
Breast Neoplasms/*epidemiology/*genetics ; Female ; Glutathione Transferase/*genetics ; Humans ; *Polymorphism, Genetic ; Research Support, Non-U.S. Gov't ; Risk Factors

OBJECTIVETo comprehensively analyse and evaluate the risk factors and to predict the trend of breast cancer in China.

METHODSCollecting the articles on case-control studies related to breast cancer in the last 10 years in China. Calculating the relative risk (OR) and 95% confidence interval (95%CI) of risk factors by the random effect model of Meta-analysis to estimate present and future population attributable risk percent (PARP) based on the exposure rate of risk factor and to predict the change of incidence rates of breast cancer during the following 5 years with the change of exposure rates.

RESULTSTwenty-two articles referred to case-control studies on breast cancer were selected. The OR and its 95%CI of the first 5 risk factors of breast cancer in China were benign breast lesion 3.39 (2.97 - 3.86), psychological stimulation 2.36 (2.09 - 2.67), breast-feeding 1.95 (1.54 - 2.47), family history of tumor 1.84 (1.63 - 2.08) and menstruation 1.65 (1.44 - 1.89). The factors with higher PRAP were benign breast lesion, breast-feeding, psychological stimulation with PRAR 15.47%, 15.17%, 13.76%, respectively. Their PRAP would have decreased to 12.77%, 11.32%, 12.52% and 9.90%, 8.74%, 9.69% respectively if the exposure rates had decreased 20% and 40% in the next 5 or 10 years. Factors contributing to the change of incidence rate of breast cancer would include benign breast lesion, breast-feeding, psychological stimulation along with the change of exposure rate. The incidence rates of breast cancer would then have become 3.09%, 2.75%, 3.03% and 6.19%, 5.50%, 6.07% respectively if their exposure rate had decreased 20% and 40% in the next 5 or 10 years.

CONCLUSIONDecreasing benign breast lesion, avoiding psychological stimulation, advocating on breast-feeding seemed to be the effective measures to control the occurrence and development of breast cancer.

Adult ; Age Factors ; Aged ; Body Weight ; Breast Diseases ; complications ; Breast Feeding ; Breast Neoplasms ; epidemiology ; etiology ; genetics ; Case-Control Studies ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; epidemiology ; Humans ; Middle Aged ; Proportional Hazards Models ; Risk Factors ; Stress, Psychological ; complications

OBJECTIVETo evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk.

METHODSA case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model.

RESULTSThe frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (< or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (> or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001).

CONCLUSIONThe findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.

Breast Neoplasms ; epidemiology ; genetics ; metabolism ; Case-Control Studies ; China ; epidemiology ; Diet ; Female ; Folic Acid ; metabolism ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Genetic ; Surveys and Questionnaires

No abstract available.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/genetics ; Carcinosarcoma/*epidemiology/genetics ; Cohort Studies ; England/epidemiology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Hormone Replacement Therapy/*statistics & numerical data ; Humans ; Incidence ; Kaplan-Meier Estimate ; Middle Aged ; Mixed Tumor, Mullerian/*epidemiology/genetics ; Mutation/genetics ; Neoplasms, Second Primary/*epidemiology ; Uterine Neoplasms/*epidemiology/genetics

Breast cancer has recently become the most common cancer in Korea. Although traditional epidemiological approaches, which are defined as "the study of the distribution and determinants of disease frequency in human population" have increased the understanding of breast cancer development in the human population, it cannot address the importance of the genetic susceptibility of humans to this disease. Therefore, a molecular epidemiological study which uses biological or genetic markers to identify and characterize the disease with the help of advances in molecular biology and human genetics might provide a better understanding of the multi-factorial or multi-step occurrence of human breast cancer. The susceptibility genes involved in the pathogenesis of breast cancer have been categorized into two groups: high penetrance genes (i.e., BRAC1, RB, etc.) and low penetrance genes (i.e., GSTs, XRCC1, etc.). This paper addresses the usefulness of biomarkers in epidemiological research of breast cancer and provides examples of the use of selected low penetrance genes involved in breast carcinogenesis in Korean women. Molecular epidemiological studies of breast cancer have enormous potential in helping researchers understand the gene-environmental interactions involved breast carcinogenesis and provide valuable insights into disease progression and survival.
Biomarkers ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Disease Progression ; Epidemiologic Studies ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Genetics, Medical ; Humans ; Korea ; Molecular Biology ; Molecular Epidemiology* ; Penetrance

The incidence of breast cancer in Korea has been increasing in recent years, such that it is now the most common female cancer. Breast cancer in Korea is characterized by an earlier age of onset than in Western countries, suggesting that it would be related with genetic background. We assayed germline mutations in the BRCA genes to evaluate their genetic pathology in Korean breast cancer patients. The study subjects consisted of 173 patients at clinically higher risk and 109 unselected patients. Germline mutations in the entire coding sequences of the BRCA1 and BRCA2 genes were analyzed by Conformation-Sensitive Gel Electrophoresis (CSGE), and any aberrantly-sized band was sequenced. BRCA mutations were present in 12.7% of the high risk patients, compared with 2.8% of the unselected patients. Among high risk patients, mutations were most prevalent in patients with a family history of breast or first-degree ovarian cancer (22.1%), followed by those with male breast cancer (20%), bilateral breast cancer (20%), multiple organ cancer including breast (13%) and younger breast cancer patients (aged<35 yr) (8.1%). Moreover, BRCA mutations were detected in 34.8% of patients having two highrisk factors. These findings suggest that BRCA gene mutation analysis should be performed on Korean patients with high-risk factors for breast cancer.
BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*epidemiology/*genetics ; Female ; Genetic Predisposition to Disease/epidemiology ; Germ-Line Mutation ; Human ; Korea/epidemiology ; *Point Mutation ; Prevalence ; Risk Factors ; Support, Non-U.S. Gov't

OBJECTIVETo study the potential effect of gene-environment interaction between CYP1A1 and serum dichlorodiphenyldichloroethane (DDT) levels on the risk of breast cancer in women, in China.

METHODSA case-control study was conducted. From Dec. 2003 to Sep. 2004, 104 women with histologically confirmed breast cancers and 154 noncancerous controls from a community were enrolled in this study. Risk factors information of breast cancer was investigated by a questionnaire. Serum p, p'-dichlorodiphenyldichloroethane (p, p'-DDT) and 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels were tested by GC-ECD. CYP1A1 m2 gene type was tested by allele special-PCR method.

RESULTSSerum DDT levels of case and control were (36.90 +/- 79.41) ng/ml and (50.60 +/- 150.70) ng/ml respectively. Serum 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels of case and control were (7.43 +/- 11.10) ng/ml and (8.96 +/- 11.30) ng/ml respectively. No statistically significant differences were found between the two groups with geometric mean t-test (P > 0.05). Compared with women who had homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 homozygous variant genotype [odds ratio (OR) = 2.61, 95% confidence interval (CI): 1.00 - 6.80]. Among premenopausal women, compared with women with homozygous wild-type of CYP1A1 genotype (Ile/Ile) and low serum DDT level (DDT serum level < or = 42.93 ng/ml), women with at least one variant allele of CYP1A1 m2 genotype and high serum DDT level (DDT serum level > or = 42.93 ng/ml) had higher risk of breast cancer (OR = 4.35, 95% CI: 1.140 - 16.950).

CONCLUSIONSCYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer while DDT exposure might have increased the risk of breast cancer among premenopausal women with CYP1A1 m2 variant genotype.

Breast Neoplasms ; epidemiology ; etiology ; genetics ; Case-Control Studies ; China ; epidemiology ; Cytochrome P-450 CYP1A1 ; genetics ; Dichlorodiphenyl Dichloroethylene ; blood ; Dichlorodiphenyldichloroethane ; blood ; Environmental Exposure ; adverse effects ; Female ; Genotype ; Homozygote ; Humans ; Insecticides ; blood ; Odds Ratio ; Polymorphism, Genetic ; Premenopause ; Risk Factors

CYP17 gene is involved in steroidogenesis and steroid metabolism. Epidemiologic results on the association between the CYP17 polymorphism and breast cancer risk have been inconsistent. We examined the association between the MspAI polymorphism at +27 relative to the start of transcription in the 5'-untranslated region of CYP17 gene and breast cancer risk in Korean women. Four hundred and sixty-two incident cases and 337 controls were recruited from three teaching hospitals in Seoul during 1994-2001. Polymorphism of the CYP17 gene was determined by a single base extension assay. Demographic and lifestyle characteristics were identified using structured questionnaire. Age-adjusted (aOR) and multivariate odds ratios (mOR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression. The proportions of A1/A1, A1/A2 and A2/A2 genotypes among controls were 20.8%, 45.1% and 34.1%, respectively. Compared to the A1/A1 genotype, A1/A2 or A2/A2 genotype was not statistically significantly associated with overall breast cancer risk (i.e., mOR=1.01, 95% CI=0.69-1.47 and mOR=0.76, 95% CI=0.51-1.14, respectively). However, a significant association between CYP17 A2/A2 genotype and breast cancer was observed among women aged 50 years or less (mOR=0.58, 95% CI=0.34-0.99, P=0.04) and leaner women (body mass index < 22 kg/m2) (mOR=0.48, 95% CI=0.23-0.97, P=0.04). Our results suggest that genetic polymorphism in 5'-untranslated region of CYP17 might play a role in breast cancer development in Korean women among younger women aged less than 50 or leaner women with body mass index less than 22 kg/m2.
5' Untranslated Regions/*genetics ; Breast/metabolism/pathology ; Breast Neoplasms/enzymology/epidemiology/*genetics ; Case-Control Studies ; Comparative Study ; Demography ; Female ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Korea/epidemiology ; Middle Aged ; Odds Ratio ; Polymorphism, Genetic/*genetics ; Questionnaires ; Research Support, Non-U.S. Gov't ; Risk Factors ; Steroid 17-alpha-Hydroxylase/*genetics