Estrogen Receptor-1 Genetic Polymorphisms for the Risk of Premature Ovarian Failure and Early Menopause

Background: The aim of this study was to investigate the role of the estrogen receptor 1 (ESR1) genetic polymorphisms for early menopause that was classified as premature ovarian failure (POF) and early menopause (EM) and to examine whether the associations of ESR1 genetic variants are different for POF and EM. Methods: We selected 100 POF cases and matched 100 EM cases and 200 normal menopause (NM) controls from the Korean Multi-Center Cohort. Among them, we restricted idiopathic POF and EM cases vs NM controls by excluding POF/EM cases with medical/surgical causes. The XbaI (rs9340799) and PvuII (rs2234693) in the ESR1 gene were genotyped. The single-nucleotide polymorphism (SNP) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis. Also nominal polytomous logistic regression was used to find whether ESR1 genetic variants are differently associated with POF and EM. Results: The global p values for idiopathic POF and EM were 0.08 and 0.39 (SNP-based), and <0.001 and 0.12 (haplotype-based), respectively. The XbaI genetic variant containing the X allele was marginally significantly associated with a reduced risk of idiopathic POF (OR=0.6, 95% CI 0.3-1.0). The P-x haplotype and diplotypes significantly decreased the risk of idiopathic POF (OR=0.5, 95% CI 0.2-0.9; OR 0.4, 95% CI 0.2-0.9, respectively). In contrast from POF, the P-x haplotypes and diplotypes insignificantly increased the risk for both idiopathic EM (p(polytomous)=0.009 for P-x haplotype; p(polytomous)=0.02 for P-x diplotypes). Conclusion: Our results suggest that the ESR1 gene including PvuII and XbaI polymorphisms may modify the risk of idiopathic premature ovarian failure (POF) but not idiopathic early menopause (EM) risk.Bretherick KL, 2008, FERTIL STERIL, V89, P318, DOI 10.1016/j.fertnstert.2007.03.008Chang SH, 2007, MATURITAS, V58, P19, DOI 10.1016/j.maturitas.2007.04.001Kitamura I, 2007, BONE, V40, P1623, DOI 10.1016/j.bone.2007.02.016Molvarec A, 2007, HYPERTENS RES, V30, P205Hsieh YY, 2007, MOL HUM REPROD, V13, P117, DOI 10.1093/molehr/gal099Dvornyk V, 2006, MATURITAS, V54, P19, DOI 10.1016/j.maturitas.2005.08.005Onland-Moret NC, 2005, CANCER CAUSE CONTROL, V16, P1195, DOI 10.1007/s10552-005-0307-5Popat RA, 2005, NEUROLOGY, V65, P383Schuit SCE, 2005, EUR J ENDOCRINOL, V153, P327, DOI 10.1530/eje.1.01973Kok HS, 2005, HUM REPROD, V20, P536, DOI 10.1093/humrep/deh600Ioannidis JPA, 2004, JAMA-J AM MED ASSOC, V292, P2105van der Klift M, 2004, J BONE MINER RES, V19, P1172, DOI 10.1359/JBMR.040215Schuit SCE, 2004, JAMA-J AM MED ASSOC, V291, P2969Wasserman L, 2004, INT J OBESITY, V28, P49, DOI 10.1038/sj.ijo.0802481van Meurs JBJ, 2003, HUM MOL GENET, V12, P1745, DOI 10.1093/hmg/ddg176Gorai I, 2003, J CLIN ENDOCR METAB, V88, P799, DOI 10.1210/jc.2002-020353Laml T, 2002, HUM REPROD UPDATE, V8, P483Herrington DM, 2002, CIRCULATION, V105, P1879, DOI 10.1161/01.CIR.0000016173.98826.88Kobayashi N, 2002, MATURITAS, V41, P193YOO KY, 2002, ASIAN PAC J CANCER P, V3, P85de Bruin JP, 2001, HUM REPROD, V16, P2014Pelletier G, 2000, J CLIN ENDOCR METAB, V85, P4835Weiderpass E, 2000, CARCINOGENESIS, V21, P623Yan G, 2000, J WOMEN HEALTH GEN-B, V9, P275Lorentzon M, 1999, J CLIN ENDOCR METAB, V84, P4597Weel AEAM, 1999, J CLIN ENDOCR METAB, V84, P3146Drummond AE, 1999, MOL CELL ENDOCRINOL, V151, P57, DOI 10.1016/S0303-7207(99)00038-6Christin-Maitre S, 1998, MOL CELL ENDOCRINOL, V145, P75Torgerson DJ, 1997, EUR J OBSTET GYN R B, V74, P63vanderSchouw YT, 1996, LANCET, V347, P714Kobayashi S, 1996, J BONE MINER RES, V11, P306NELSON LM, 1996, REPROD ENDOCRINOLOGY, P1394KAPRIO J, 1995, HUM BIOL, V67, P739CRAMER DW, 1995, FERTIL STERIL, V64, P740EXCOFFIER L, 1995, MOL BIOL EVOL, V12, P921NELSON LM, 1994, J CLIN ENDOCR METAB, V79, P1470CAPLAN GA, 1994, J ROY SOC MED, V87, P200PALMER JR, 1992, AM J EPIDEMIOL, V136, P408BAGUR AC, 1992, CALCIFIED TISSUE INT, V51, P4FRANCESCHI S, 1991, INT J CANCER, V49, P57MEYER JM, 1991, AM J MED GENET, V39, P148TRELOAR SA, 1990, AM J HUM GENET, V47, P137SNOWDON DA, 1989, AM J PUBLIC HEALTH, V79, P709

Radiological Spectrum of Hepatic Mesenchymal Hamartoma in Children

OBJECTIVE: A hepatic mesenchymal hamartoma is an uncommon benign tumor in children and little is known about the spectrum of its radiological features. The purpose of this study is to describe the spectrum of radiological features of a hepatic mesenchymal hamartoma in children. MATERIALS AND METHODS: Thirteen children with a pathologically confirmed hepatic mesenchymal hamartoma (M:F = 7:6; mean age, 3 years 2 months) were included in our study. Ultrasonography (US) was performed in nine patients including color and power Doppler US (n = 7). CT scans were performed in all patients. We evaluated the imaging findings of the hepatic mesenchymal hamartomas and the corresponding pathological features. RESULTS: Each patient had a single tumor (mean diameter: 13 cm [1.8-20 cm]). On CT and/or US, four patients (31%) had a "multiseptated cystic tumor", five patients (38%) had a "mixed solid and cystic tumor", and four patients (31%) had a "solid tumor." The septa of the cystic portion were thin in the multiseptated cystic tumors and irregularly thick in the mixed solid and cystic tumors as seen on US. On a post-contrast CT scan, solid portions or thick septa of the tumors showed heterogeneous enhancement. The amount of hepatocytes was significantly different among the three tumor groups according to the imaging spectrum (p = 0.042). CONCLUSION: A hepatic mesenchymal hamartoma in children can show a wide spectrum of radiological features, from a multiseptated cystic tumor to a mixed solid and cystic tumor, and even a solid tumor

Association between Body Mass Index and Gastric Cancer Risk According to Effect Modification by Helicobacter pylori Infection

Purpose Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information. Materials and Methods We performed a case-cohort study (n=2,458) that consists of a subcohort (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model. Results Increased GC risk in lower BMI group (= 25 kg/m(2)) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori. Conclusion This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.Peer reviewe

Oncogenic CagA Promotes Gastric Cancer Risk via Activating ERK Signaling Pathways: A Nested Case-Control Study

Background: CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer. Methods: In the discovery phase, a total of 580 SNPs within +/-5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets). The most significant SNPs (raw or permutated p value??0.02) identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets). Combined analyses including pooled-and meta-analysis were conducted to summarize all the results. Results: 24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk) were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p??0.05). In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19-2.06], OR = 0.61, [95% CI: 0.43-0.87], OR = 0.59, [95% CI: 0.54-0.76], respectively). Conclusions: Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis

The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the role of <it>TNF </it>genetic variants and the combined effect between <it>TNF </it>gene and cigarette smoking in the development of gastric cancer in the Korean population.</p> <p>Methods</p> <p>We selected 84 incident gastric cancer cases and 336 matched controls nested within the Korean Multi-Center Cancer Cohort. Six SNPs on the <it>TNF </it>gene, <it>TNF</it>-α-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C, and <it>TNF</it>-β 252 A/G were genotyped. The ORs (95% CIs) were calculated using unconditional logistic regression model to detect each SNP and haplotype-pair effects for gastric cancer. The combined effects between the <it>TNF </it>gene and smoking on gastric cancer risk were also evaluated. Multi dimensionality reduction (MDR) analyses were performed to explore the potential <it>TNF </it>gene-gene interactions.</p> <p>Results</p> <p><it>TNF</it>-α-857 C/T containing the T allele was significantly associated with an increased risk of gastric cancer and a linear trend effect was observed in the additive model (OR = 1.6, 95% CI 1.0–2.5 for CT genotype; OR = 2.6, 95% CI 1.0–6.4 for TT genotype). All haplotype-pairs that contained TCT or CCC of <it>TNF</it>-α-1031 T/C, <it>TNF</it>-α-863 C/A, and <it>TNF</it>-α-857 C/T were associated with a significantly higher risk for gastric cancer only among smokers. In the MDR analysis, regardless of smoking status, <it>TNF</it>-α-857 C/T was included in the first list of SNPs with a significant main effect.</p> <p>Conclusion</p> <p><it>TNF</it>-α-857 C/T polymorphism may play an independent role in gastric carcinogenesis and the risk for gastric cancer by <it>TNF </it>genetic effect is pronounced by cigarette smoking.</p

Genetic Susceptibility on CagA-Interacting Molecules and Gene-Environment Interaction with Phytoestrogens: A Putative Risk Factor for Gastric Cancer

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk