Lian-Hua Cui

Relative contribution of body composition to bone mineral density at different sites in men and women of South Korea

We examined the relative contribution of body composition to bone mineral density (BMD) at various sites in 1406 Korean rural men and women, aged 19–80 years, from July to August 2004. The BMD was measured at peripheral (distal forearm and calcaneus) and central (lumbar spine at L1–L4, femoral neck, trochanter, and Wards triangle) using dual-energy X-ray absorptiometry. In multivariate analyses, the linear regression models were adjusted for relevant covariates. In premenopausal women, only lean mass had a significant positive correlation with BMD at all sites. In postmenopausal women, fat mass was significantly positively correlated with BMD at all sites, except the Wards triangle; fat mass was the only determinant of BMD at the lumbar, distal forearm, and calcaneus sites, whereas both lean and fat mass contributed to BMD at the hip, with the effect of lean mass being slightly greater than that of fat mass. In younger men, lean mass had a significant positive contribution to BMD at all sites, whereas fat mass appeared to contribute negatively to BMD at all sites, except the calcaneus. In older men, lean mass made a significant positive contribution to the BMD at all sites; fat mass also made a significant positive contribution to the BMD at the forearm and calcaneus. These data indicate that in the Korean rural population, lean mass may be an important determinant of the BMD, whereas fat mass may contribute positively to BMD only in postmenopausal women and older men.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

BackgroundThis study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population.MethodsWe conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis.ResultsThe MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer.ConclusionsThe T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.

Prevalence of osteoporosis and reference data for lumbar spine and hip bone mineral density in a Korean population

The aims of this study were to establish reference data for bone mineral density (BMD) at central skeletal sites using Lunar dual-energy X-ray absorptiometry (DXA), and to estimate the age-and sex-specific prevalence of osteoporosis in a Korean population. We performed a population-based, cross-sectional study. The subjects were 4148 (1810 men and 2338 women) Korean adults, aged 20–79 years. The BMD for central sites (lumbar spine, femoral neck, trochanter, and Ward’s triangle) were measured by DXA. The standardized prevalence of osteoporosis among individual aged 50–79 years in lumbar spine, femoral neck, Ward’s triangle, and trochanter was 40.1%, 12.4%, 28.4%, and 4.4% in women and 6.5%, 5.9%, 3.7%, and 1.6% in men, respectively. In women, peak BMD occurred in the age range 40–49 years for the femoral neck and trochanter, 30–39 years for the lumbar spine, and 20–29 years for Ward’s triangle. In men, peak BMD values were observed at 20–29 years for all measured sites. This study establishes a normative database for BMD at central skeletal sites using dualenergy X-ray absorptiometry and provides more reliable information on the prevalence of osteoporosis in Korea.

Influence of polymorphisms in MTHFR 677 C→T, TYMS 3R→2R and MTR 2756 A→G on NSCLC risk and response to platinum-based chemotherapy in advanced NSCLC

AIMS Genetic factors may contribute to individual differences in cancer susceptibility, drug efficacy and toxicity. This study was designed to investigate the effects of the polymorphisms of methylenetetrahydrofolate reductase 677 C→T (MTHFR 677 C→T), thymidylate synthase (TYMS 3R→2R),and methionine synthase 2756 A→G (MTR 2756 A→G) on the risk of lung cancer and response to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). MATERIALS & METHODS We conducted a case-control study involving 438 NSCLC cases (including 101 follow-up cases) and 641 healthy controls in North China. RESULTS & CONCLUSION Using a genetic model analysis, the polymorphism MTHFR 677 C→T showed a significantly increased risk for NSCLC in women but not in men, which was observed in the codominant model (CT vs CC adjusted odds ratio [OR] = 2.46; 95% confidence interval [CI]: 1.37-4.42; p = 0.003; TT vs CC adjusted OR: 2.04; 95% CI: 1.09-3.81; p = 0.03) and the dominant model (CT + TT vs CC adjusted OR: 2.30; 95% CI: 1.31-4.05; p = 0.004). In addition, we found that patients with the MTHFR 677 TT genotype showed a better response to platinum-based chemotherapy in the recessive model (TT vs CT + CC adjusted OR: 0.24; 95% CI: 0.09-0.68; p = 0.007), the generalized OR was 0.44 (0.22-0.88; p = 0.04). There were no significant associations of the polymorphisms of TYMS 3R→2R or MTR 2756 A→G with the risk of NSCLC or response to platinum-based chemotherapy in advanced NSCLC in any genetic model. Our results suggest that genetic polymorphisms of MTHFR 677 C→T may contribute to NSCLC development in Chinese women and could also influence treatment response for advanced NSCLC patients with platinum-based chemotherapy. Further studies with larger sample sizes are required to validate this association.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population

BackgroundThis study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population.MethodsWe conducted a large-scale, case-control study involving 3938 patients with newly diagnosed lung cancer and 1700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. Statistical significance was estimated by logistic regression analysis.ResultsThe MTHFR C677T frequencies of CC, CT, and TT genotypes were 34.5%, 48.5%, and 17% among lung cancer patients, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677CT and TT genotype showed a weak protection against lung cancer compared with the homozygous CC genotype, although the results did not reach statistical significance. The age- and gender-adjusted odds ratio (OR) of overall lung cancer was 0.90 (95% confidence interval (CI), 0.77-1.04) for MTHFR 677 CT and 0.88 (95% CI, 0.71-1.07) for MTHFR 677TT. However, after stratification analysis by histological type, the MTHFR 677CT genotype showed a significantly decreased risk for squamous cell carcinoma (age- and gender-adjusted OR, 0.78; 95% CI, 0.64-0.96). The combination of 677 TT homozygous with 677 CT heterozygous also appeared to have a protection effect on the risk of squamous cell carcinoma. We observed no significant interaction between the MTHFR C677T polymorphism and age and gender or smoking habit.ConclusionsThis is the first reported study focusing on the association between MTHFR C677T polymorphisms and the risk of lung cancer in a Korean population. The T allele was found to provide a weak protective association with lung squamous cell carcinoma.

Dietary Fibre and the Risk of Colorectal Cancer: a Case- Control Study

BACKGROUND Colorectal cancer is one of the most commonly occurring cancers in China. Dietary fibre has been thought to decrease the risk of colorectal cancer in Western countries. However, studies investigating the association between dietary fibre (particularly soluble and insoluble fibres) and colorectal cancer have hitherto been lacking in China. OBJECTIVE This case-control study examined the effect of dietary fibre intake on the risk of colorectal cancer, stratified by tumour site. MATERIALS AND METHODS The study included 265 cases (colon cancer, 105; rectal cancer, 144; colon and rectal cancer, 16) and 252 controls residing in Qingdao. A food frequency questionnaire that included 121 food items was used to collect dietary information. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis. RESULTS For food groups, controls in the study consumed more vegetables, soy food and total fibre than did colorectal cancer patients (p<0.05). The intakes of fruit, meat and sea-food did not differ significantly between cases and controls. However, we did not find any association between soy food intake and colon cancer. We observed inverse associations between total fibre intake and colorectal, colon and rectal cancer (Q4 vs Q1: OR=0.44, 95%CI, 0.27- 0.73; OR=0.40, 95%CI, 0.21-0.76; OR=0.52, 95%CI, 0.29-0.91). Vegetable fibre intake showed similar inverse associations (Q4 vs Q1: OR=0.51, 95%CI, 0.31-0.85; OR=0.48, 95%CI, 0.25-0.91; OR=0.53, 95%CI, 0.29-0.97). In addition, inverse associations were observed between soluble fibre and insoluble fibre and both colorectal cancer and colon cancer. No relationship was found between colorectal cancer and fruit, soy or grain fibre intakewhen the results were stratified by tumour site. CONCLUSIONS The present study suggests that vegetable fibre and total fibre play very important roles in protecting against colorectal cancer. Soluble and insoluble fibres were inversely associated with only colorectal cancer and colon cancer.

Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods

In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are frequently- used lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

Lack of effects of dietary folate intake on risk of breast cancer: an updated meta-analysis of prospective studies.

BACKGROUND Epidemiological findings are controversial relating to the relationship between dietary folate intake and the risk of breast cancer. We therefore conducted a meta-analysis of prospective cohort studies to clarify this association. MATERIALS AND METHODS PUPMED, EMBASE, and MEDLINE databases were searched for all relevant literature published in English from January 1, 1966 to August 2013. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using a fixed or random effects model. RESULTS Dietary folate intake was not significantly associated with the risk of breast cancer. The combined PR with 95% CI for the highest vs. lowest category dietary intake of folate [fifteen studies; 1,836,566 participants and 24,083 patients with breast cancer] was 0.98 (0.90-1.05). Among subgroup analysis by menstrual status, hormonal status and the consumption of alcohol, methionine and vitamin B12, no significant association was observed for the dietary intake of folate and the risk of breast cancer. Dose-response analysis showed that a 220 μg/day increment in dietary folate intake was not associated with the risk of breast cancer. CONCLUSIONS Our findings indicate that dietary folate intake has no significant effect on the risk of breast cancer.

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.

Glutathione-S-transferase (GSTM1, GSTT1) Null Phenotypes and Risk of Lung Cancer in a Korean Population

PURPOSE The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes with the risk of lung cancer in a South Korean population. METHODS We conducted a large-scale, population-based case-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 were determined using real-time polymerase chain reaction. RESULTS In logistic regression analysis adjusted for age and smoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men, the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 for GSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferred an increased risk for LC in men (OR=1.39, 95% CI=1.08-1.78). The OR for the GSTT1 null genotype was greater in subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97-1.90 for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66-1.12 for women) in both genders (p for interaction <0.05). CONCLUSIONS In the Korean population, the GSTM1 and GSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effect on LC risk in younger people (age 55 years and under) than in older individuals.