Sue Kyung Park

Genetic Polymorphisms of Selected DNA Repair Genes, Estrogen and Progesterone Receptor Status, and Breast Cancer Risk

Purpose: Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of breast cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women. Experimental Design: We included 872 incident breast cancer cases and 671 controls recruited from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of selected DNA repair genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg188His, XRCC4 921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C > T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 −93G > A, and Ile219Val). Results: We found that the RAD52 2259 CT or TT, hMLH1 −93 GG, and ERCC1 8092 AA genotypes were associated with breast cancer risk after adjustment for known risk factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR, 1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When Bonferronis method was used to correct for multiple comparisons for nine polymorphisms with P = 0.005, all of these associations were not significant. However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were more evident for the estrogen/progesterone receptor–negative cases (OR, 2.03; 95% CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively). Conclusion: Our findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be associated with breast cancer risk in Korean women.

Estrogen receptor alpha gene polymorphisms and breast cancer risk

We conducted a hospital-based case-control study to evaluate the association between the XbaI and PvuII restriction fragment length polymorphisms (RFLPs) in intron 1 of the estrogen receptor α (ERα) gene and breast cancer risk. The study population consisted of 205 histologically confirmed incident breast cancer cases and 205 age-matched controls with no present and previous history of cancer. The PvuII genotype distribution did not show any difference between cases and controls, but the adjusted odds ratio (OR) for the XbaI X allele containing genotypes was 0.4 (95% CI: 0.3–0.6) compared with the xx genotype. The decrease in the OR appeared to be more attributable to the postmenopausal women; the ORs were 0.3 (95% CI: 0.1–0.5) and 0.5 (95% CI: 0.3–0.9) for postmenopausal and premenopausal women, respectively. Our results therefore suggest that the ERα XbaI polymorphism modifies individual susceptibility to breast cancer in Korean women.

Genetic Polymorphisms of Ataxia Telangiectasia Mutated and Breast Cancer Risk

To evaluate the role of genetic polymorphisms of ataxia telangiectasia mutated (ATM) in the etiology of breast cancer, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident breast cancer cases and 1,181 cancer-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the ATM polymorphisms-5144A>T, IVS21+1049T>C, IVS33−55T>C, IVS34+60G>A, and 3393T>G were determined by the 5′-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five ATM alleles were found to be in strong linkage disequilibrium (D′ > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (χ2 test, P < 0.001). The ATM IVS21+1049 TC or CC, IVS34+60 GA or AA, and 3393 TG or GG genotypes were associated with increased breast cancer risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of breast cancer with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with increased breast cancer risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of breast cancer, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of breast cancer increased (P for trend <0.01). Our results thus suggest that genetic polymorphisms of ATM play an important role in the development of breast cancer in Korean women.

Prevalence and epidemiologic characteristics of urolithiasis in Seoul, Korea

OBJECTIVES To study the epidemiologic details of urolithiasis in Seoul, Korea. The prevalence of urolithiasis varies by different regions in the world and has been reported to be 4% to 15%. METHODS A total of 2643 persons 40 to 79 years old living in Seoul were selected by stepwise random sampling. Questionnaires were used and completed by trained interviewers concerning whether the subjects had experienced urinary stone disease at any time in their life. RESULTS Of 2643 persons interviewed, 65 experienced 78 episodes of urinary stone formation in their lifetime. Calibrated after the Seoul population census, the overall standardized lifetime prevalence rate was estimated to be 3.5%, 6.0% in men and 1.8% in women. The point prevalence rate was estimated to be 0.9%, 1.9% in men and 0.3% in women. Most of the urinary stone diseases were diagnosed at the fifth decade. Kidney stones in family members were present in 8.1% of patients with stones and 4.1% of stone-free control individuals. Twenty percent of the patients with stones experienced recurrences. CONCLUSIONS In this first systematically assessed epidemiologic survey about the rate of urolithiasis in Korea, 6.0% of Korean men and 1.8% of women are expected to experience urinary stone disease during their lifetime.

Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk

We conducted a hospital-based case–control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P ≤ 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.

Prevalence and risk factors of distal radius and calcaneus bone mineral density in Korean population

To estimate the prevalence and the related risk factors of low bone mineral density of the calcaneus and the distal radius, a community-based study was conducted in three rural areas of Korea. A total of 1420 women and 732 men aged 40 years and older participated in this study. Information on sociodemographic characteristics and the potential risk factors for osteoporosis were collected by an interviewer-administered standardized questionnaire. Bone mineral density (BMD) of the calcaneus and the distal radius were measured by dual-energy X-ray absorptiometry (DXA). Three hundred and seventeen women and 183 men aged 20–29 years who participated in a regular health check-up were used as a reference population. Osteoporosis was defined using WHO criteria. Odds ratios of the risk factors of osteoporosis were calculated by the unconditional logistic regression model. The standardized prevalence of osteoporosis of the calcaneus was 8.4% for males and 27.3% for females using the Korean population of year 2000 as a standard population. The standardized prevalence of osteoporosis of the distal radius was 4.2% for males and 18.8% for females. Older age and lower body mass index (BMI) were related with low BMD in both the calcaneus and distal radius in males and females. The duration after menopause and the number of live births were an independent risk factor for osteoporosis of the calcaneus (OR=1.1, 95% CI=1.00–1.11; the duration after menopause; OR=2.0, 95% CI=1.20–3.35, the number of live birth) and a familial history of non-traumatic fractures or osteoporosis among the first-degree relatives was significantly related to a increased risk of osteoporosis of the distal radius in females (OR=2.9, 95% CI=1.36–6.31).

Genetic polymorphisms of TGF-β1 & TNF-β and breast cancer risk

AbstractObjective. The proliferation of malignant breast epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes may modify the breast cancer risk. To evaluate the potential influences of TGF-β1 T29C and TNF-β A252G gene polymorphisms on breast cancer risk, a case–control study was conducted in Korea. Methods. Histologically confirmed breast cancer cases (n = 560) and controls (n=509) with no previous history of cancer were recruited from three teaching hospitals in Seoul, Korea. Genotypes were determined by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model adjusting for age, body mass index, education, parity, age at first full-term pregnancy, and family history of breast cancer. Results. The TGF-β1 29C-allele containing genotypes posed an increased risk of breast cancer (OR=1.3, 95% CI=1.02–1.79), especially in postmenopausal women (OR=1.6, 95% CI=1.01–2.44). Similarly, the TNF-β252G-allele containing genotypes posed an increased risk of postmenopausal breast cancer (OR=1.7, 95% CI=1.09–2.55). The risk of postmenopausal breast cancer increased in parallel with the number of the risk genotypes (p for trend <0.01). When data were stratified by the presumed non-genetic risk factors, TGF-β1 C-allele containing genotypes were found to increase breast cancer risk almost two-fold in postmenopausal women with greater than median body mass index (>22.8 kg/m2) (OR=1.9, 95% CI=1.04–3.37). Conclusion. The results of this study therefore suggest that polymorphisms of TGF-β1 and TNF-β genes may modify individual susceptibility to breast cancer in Korean women.

Genetic polymorphisms of TGF-?1 & TNF-? and breast cancer risk

AbstractObjective. The proliferation of malignant breast epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes may modify the breast cancer risk. To evaluate the potential influences of TGF-β1 T29C and TNF-β A252G gene polymorphisms on breast cancer risk, a case–control study was conducted in Korea. Methods. Histologically confirmed breast cancer cases (n = 560) and controls (n=509) with no previous history of cancer were recruited from three teaching hospitals in Seoul, Korea. Genotypes were determined by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model adjusting for age, body mass index, education, parity, age at first full-term pregnancy, and family history of breast cancer. Results. The TGF-β1 29C-allele containing genotypes posed an increased risk of breast cancer (OR=1.3, 95% CI=1.02–1.79), especially in postmenopausal women (OR=1.6, 95% CI=1.01–2.44). Similarly, the TNF-β252G-allele containing genotypes posed an increased risk of postmenopausal breast cancer (OR=1.7, 95% CI=1.09–2.55). The risk of postmenopausal breast cancer increased in parallel with the number of the risk genotypes (p for trend <0.01). When data were stratified by the presumed non-genetic risk factors, TGF-β1 C-allele containing genotypes were found to increase breast cancer risk almost two-fold in postmenopausal women with greater than median body mass index (>22.8 kg/m2) (OR=1.9, 95% CI=1.04–3.37). Conclusion. The results of this study therefore suggest that polymorphisms of TGF-β1 and TNF-β genes may modify individual susceptibility to breast cancer in Korean women.

CHAPTER 26:Isoflavones against Gastric Cancer: Function and Effects

Due to the chemical structure similarity between isoflavones and 17β-estradiol, isoflavones act either as estrogen agonists or antagonists, depending on endocrine estrogenic levels. Interest in isoflavones has come into focus resulting from reports of the positive health benefits associated with their consumption in the prevention of diseases, particularly hormone-dependent cancers, cardiovascular diseases, osteoporosis, and adverse postmenopausal symptoms. In addition to its estrogenic effect, isoflavones also have positive effects on non-hormone-related diseases. The evidence that isoflavones have beneficial effect in combating gastric cancer has been suggested by in vivo, in vitro, and epidemiologic studies. Based upon meta-analysis review of existing original articles, this Chapter provides an overview of the plausible biological functions of isoflavones as they relate to their beneficial effects on gastric cancer in human subjects.