Aquamicrobium zhengzhouense sp. nov., a Bacterium Isolated from Farmland Soil Applied with Amino Acid Fertilizer.

A novel Gram-stain-negative, rod-shaped, strictly aerobic, non-motile bacterium, designated strain cd-1T, was isolated from a farmland soil applied with amino acid fertilizer in Zhengzhou, Henan province, China. The optimum growth of strain cd-1T occurred at 30 °C, pH 7.0 in Luria-Bertani (LB) broth without NaCl supplement. Phylogenetic analysis based on 16S rRNA gene sequences indicated that cd-1T is member of the genus Aquamicrobium, and formed a separate branch with Aquamicrobium aerolatum DSM 21857T (96.5%) and Aquamicrobium soli KCTC 52165T (95.7%). The draft genome sequencing revealed a DNA G + C content of 59.2 mol% and Q-10 was the predominant respiratory quinone. The major cellular fatty acids were identified as C18:1 ω7c (35.8%), C19:0 cyclo ω8c (32.1%), and C18:1 ω7c 11-methyl (5.2%). The polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and phosphatidylmonomethylethanolamine. Average nucleotide identity (ANI) and the digital DNA-DNA hybridizations (dDDH) for draft genomes between strain cd-1T and KCTC 52165T were 71.0% and 19.9%, respectively, the values for strain cd-1T and DSM 21857T were 73.4% and 20.6%. Based on the physiological and biochemical characteristics, phylogenetic and chemotaxonomic analysis, strain cd-1T is considered to represent a novel species of the genus Aquamicrobium, for which the name Aquamicrobium zhengzhouense sp. nov. is proposed. The type strain is cd-1T (= KCTC 82182T = CCTCC M 2018904T).

Re-evaluation of ABO gene polymorphisms detected in a genome-wide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population.

Pancreatic cancer is a fatal malignancy with an increasing incidence in Shanghai, China. A genome-wide association study (GWAS) and other work have shown that ABO alleles are associated with pancreatic cancer risk. We conducted a population-based case-control study involving 256 patients with pathologically confirmed pancreatic ductal adenocarcinoma (PDAC) and 548 healthy controls in Shanghai, China, to assess the relationships between GWAS-identified ABO alleles and risk of PDAC. Carriers of the C allele of rs505922 had an increased cancer risk [adjusted odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.02-1.98] compared to TT carriers. The T alleles of rs495828 and rs657152 were also significantly associated with an elevated cancer risk (adjusted OR = 1.58, 95% CI: 1.17-2.14; adjusted OR = 1.51, 95% CI: 1.09-2.10). The rs630014 variant was not associated with risk. We did not find any significant gene-environment interaction with cancer risk using a multifactor dimensionality reduction (MDR) method. Haplotype analysis also showed that the haplotype CTTC was associated with an increased risk of PDAC (adjusted OR = 1.46, 95% CI: 1.12-1.91) compared with haplotype TGGT. GWAS-identified ABO variants are thus also associated with risk of PDAC in the Chinese population.

Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.

Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.

Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: a population-based study in Shanghai, China.

BACKGROUND AND AIM: Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones. METHODS: We investigated the associations between nine single nucleotide polymorphisms in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct, and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China. RESULTS: We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odds ratio = 2.37, 95% confidence interval (CI): 1.36-4.14) compared with subjects with the TT genotype, and remained significant after Bonferroni correction (P = 0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (odds ratio = 0.61, 95% confidence interval: 0.43-0.86) compared with those with the G-C-C-A haplotype; the association also remained significant after Bonferroni correction. CONCLUSIONS: These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.

Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China.

Biliary tract cancers are rare but fatal malignancies, with increasing incidence in Shanghai, China. Gallstones, the primary risk factor for biliary tract cancer, typically result from oversaturation of cholesterol in bile. We examined the association of five variants in three lipid metabolism-related genes (CETP, ABCG8 and LRPAP1) and biliary tract cancers and stones in a population-based case-control study in Shanghai, China. We included 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases and 447 population controls. Carriers of the CG genotype of ABCG8 rs11887534 had higher risk of biliary stones [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.82-6.5), gallbladder cancer (OR = 4.3, 95% CI 1.7-10.4) and bile duct cancer (OR = 1.94, 95% CI 0.64-5.91), compared with carriers of the GG genotype. Analysis stratified by gender showed both male and female carriers of CG rs11887534 had higher risks of biliary stones and gallbladder cancer, although the association was statistically significant only for women and gallbladder cancer (OR = 6.3, 95% CI 1.86-22.3). Carriers of the ABCG8 haplotype C-C (rs4148217-rs11887534) had a 4.16-fold (95% CI 1.71-10.1) risk of gallbladder cancer compared with those carrying the C-G haplotype. Our findings suggest that ABCG8 rs11887534, identified as a gallstone risk single-nucleotide polymorphism by whole genome scan, is also associated with an increased risk of biliary tract cancer.

Association of a single nucleotide polymorphism at 6q25.1,rs2046210, with endometrial cancer risk among Chinese women.

A recent genome-wide association study identified a new susceptibility locus for breast cancer, rs2046210, which is a single nucleotide polymorphism (SNP) located upstream of the estrogen receptor α(ESR1) gene on chromosome 6q25.1. Given that endometrial cancer shares many risk factors with breast cancer and both are related to estrogen exposure and that rs2046210 is in close proximity to the ESR1 gene, we evaluated the association of SNP rs2046210 with endometrial cancer risk among 953 cases and 947 controls in a population-based, case-control study conducted in Shanghai, China. Logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for potential confounders. We found that the A allele of rs2046210, linked to an increased risk of breast cancer, was associated with increased but not statistically significant risk of endometrial cancer (OR = 1.16, 95% CI = 0.96-1.41 for the GA and AA genotypes compared with the GG genotype); the association was stronger among post-menopausal women (OR = 1.28, 95% CI = 1.00-1.65). The association tended to be stronger among women with higher or longer estrogen exposure than among women with relatively lower or shorter exposure to estrogen. Our study suggests that rs2046210 may play a role in the etiology of endometrial cancer. Additional studies are needed to confirm our findings.

Association of thymidylate synthase gene with endometrial cancer risk in a Chinese population.

We comprehensively evaluated genetic variants in the thymidylate synthase (TYMS) gene in association with endometrial cancer risk in a population-based case-control study of 1,199 incident endometrial cancer cases and 1,212 age frequency-matched population controls. Exposure information was obtained via in-person interview, and DNA samples (blood or buccal cell) were collected. Genotyping of 11 haplotype-tagging single nucleotide polymorphisms (SNP) for the TYMS gene plus the 5-kb flanking regions was done for 1,028 cases and 1,003 controls by using the Affymetrix MegAllele Targeted Genotyping System. Of 11 haplotype-tagging SNPs identified, 7 that are located in flanking regions of the TYMS gene are also in the ENOSF1 (rTS) gene. The SNP rs3819102, located in the 3'-flanking region of the TYMS gene and in an intron of the ENOSF1 gene, was associated with risk of endometrial cancer. The odds ratio (95% confidence interval) for the CC genotype was 1.5 (1.0-2.2) compared with the TT genotype. Haplotype TTG in block 2 of the TYMS gene, which includes SNPs rs10502289, rs2298583, and rs2298581 (located in introns of the ENOSF1 gene), was associated with a marginally significant decrease in risk of endometrial cancer under the dominant model (odds ratio, 0.8; 95% confidence interval, 0.6-1.0). This study suggests that genetic polymorphisms in the TYMS or ENOSF1 genes may play a role in the development of endometrial cancer among Chinese women.

The Asp(327)Asn polymorphism in the sex hormone-binding globulin gene modifies the association of soy food and tea intake with endometrial cancer risk.

We evaluated the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls. Genotyping of polymorphisms was performed by using TaqMan (Applied Biosystems, Foster City, CA) assays (rs6259) or the Affymetrix MegAllele Targeted Genotyping System (Affymetrix, Inc., US) (rs13894, rs858521, and rs2955617). Dietary information was obtained using a validated food frequency questionnaire. A logistic regression model was employed to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found that the Asp(327)Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62-1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soy isoflavones and tea intake). This study suggests that gene-diet interaction may play an important role in the etiology of endometrial cancer risk.

Interaction of soy food and tea consumption with CYP19A1 genetic polymorphisms in the development of endometrial cancer.

Certain polyphenols inhibit the activity of aromatase, a critical enzyme in estrogen synthesis that is coded by the CYP19A1 gene. Consumption of polyphenol-rich foods and beverages, thus, may interact with CYP19A1 genetic polymorphisms in the development of endometrial cancer. The authors tested this hypothesis in the Shanghai Endometrial Cancer Study (1997-2003), a population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls. Dietary information was obtained by use of a validated food frequency questionnaire. Genotypes of CYP19A1 at rs28566535, rs1065779, rs752760, rs700519, and rs1870050 were available for 1,042 cases and 1,035 controls. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals after adjustment for potential confounding factors. Higher intake of soy foods and tea consumption were both inversely associated with the risk of endometrial cancer, with odds ratios of 0.8 (95% confidence interval: 0.6, 1.0) for the highest versus the lowest tertiles of intake of soy and 0.8 (95% confidence interval: 06, 0.9) for ever tea consumption. The association of single nucleotide polymorphisms rs1065779, rs752760, and rs1870050 with endometrial cancer was modified by tea consumption (p(interaction) < 0.05) but not by soy isoflavone intake. The authors' findings suggest that tea polyphenols may modify the effect of CYP19A1 genetic polymorphisms on the development of endometrial cancer.

Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women.

Folate plays an important role in carcinogenesis. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), encoded by the MTHFR gene, is involved in this process. We investigated both the independent and joint effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk in a population-based case-control study. Between 1997 and 2003, 1,204 newly diagnosed endometrial cancer cases and 1,212 controls were recruited among women between the ages of 30 and 69 years in urban Shanghai, China. Information on dietary intake of folate and other methyl-related nutrients, including vitamin B2 (riboflavin), vitamin B6, vitamin B12, and methionine, was derived from a validated food frequency questionnaire. Genotyping was completed on 1,041 cases and 1,030 controls for MTHFR 677C>T (rs1801133), 1298A>C (rs1801131), and 1793 G>A (rs2274967) [corrected] Haplotype estimation of the three single-nucleotide polymorphisms was performed using PHASE software. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate associations of nutrients, MTHFR genotypes, and haplotypes with endometrial cancer risk. A significant inverse association between dietary folate intake and endometrial cancer risk was observed among all subjects and non-B vitamin supplement users. The greatest reduction in endometrial cancer risk was observed among non-users of supplements in the highest quartile of dietary folate intake (OR, 0.5; 95% CI, 0.4-0.7) as compared with those in the lowest quartile. Dietary intake of folate cofactors (methionine, vitamin B2, vitamin B6, and vitamin B12) was not related to risk of endometrial cancer. No association was observed between endometrial cancer and the MTHFR 677C>T, 1298 A>C, and 1793G>A polymorphisms or derived haplotypes. Among non-users of supplements, however, the 1298C and 1793A alleles were associated with a lower risk of endometrial cancer among women with high dietary folate intake but related to a higher risk among those with low dietary folate intake (P(interaction) = 0.08 and 0.03, respectively). Further analysis showed that the lowest risk (OR, 0.6; 95% CI, 0.4-1.1) was among women with the 1298C allele and the highest intake of both folate and riboflavin (P(interaction) = 0.04). A similar association was observed for the 1793A allele (P(interaction) = 0.03). Our findings suggest that folate intake may decrease the risk of endometrial cancer and modify the effect of MTHFR polymorphisms on risk.

[A case-control study on genetic polymorphism of CYP17 MspA(1)I and its association with endometrial cancer risk].

OBJECTIVE: To assess whether the polymorphisms of CYP17 MspA(1)I are associated with the susceptibility of endometrial cancer. METHODS: The allelic discrimination of the CYP17A1 gene polymorphisms were assessed with the ABI PRISM 7900 Sequence Detection Systems using TaqMan genotyping assay. Unconditional logistic regression was applied to assess odds ratio and 95% CI and evaluate the association between different genotypes and endometrial cancer development. RESULTS: The frequencies of wild-type, heterozygote and homozygote for the CYP17 MspA(1)I in control women in Shanghai were 17.8%, 49.3% and 32.9%, respectively. No significant difference was found in the distribution of various genotypes of CYP17 MspA(1)I between patients and controls. Pregnancy was associated with reduced risk of endometrial cancer in pre-menopausal women with A2 allele, OR = 0.66, 95% CI: 0.44 approximately 0.99. In post-menopausal women with A2 allele, more pregnancies ( > 2) and shorter time of menstruation ( < or = 32 yrs) were associated with reduced risk of endometrial cancer. CONCLUSION: No significant relationship was found between CYP17 MspA(1)I genotypes and endometrial cancer risk.

Weight history and risk of endometrial cancer among Chinese women.

BACKGROUND: Adult obesity is a well-established risk factor for endometrial cancer. However, little is known about the association of endometrial cancer risk with body size early in life and weight change during adulthood. We investigated whether women with greater early-age body size or with greater weight change during adulthood have an increased risk of endometrial cancer. METHODS: We analysed data from a population-based case-control study of endometrial cancer conducted between 1997 and 2001 in Shanghai, China. Included in this analysis were 832 endometrial cancer cases aged 30-69 years and 846 population controls. Information on weight and height history from adolescence through adulthood was obtained via structured in-person interviews. A logistic regression model was used to derive odds ratios (ORs) and 95% confidence intervals (CIs) for endometrial cancer in association with adolescent and adult adiposity, as well as adult body weight change. All ORs were adjusted for age, education, menstrual status, duration of menstruation, number of pregnancies, oral contraceptive use, and family history of cancer. RESULTS: Perceived weights and heights during puberty that were greater than average were associated with a modestly increased risk of cancer. The association for perceived weight was substantially weakened after adjustment for current body mass index (BMI). High BMI at all adult ages significantly predicted endometrial cancer risk, with recent BMI being the strongest predictor. Further analyses disclosed that weight gain during adulthood, particularly during the peri-menopausal period (age 40-50 years), was associated with a significantly elevated risk of endometrial cancer, even among currently non-obese women. Gaining >5 kg between age 40 and 50 was related to ORs of 2.3 (95% CI 1.4-3.9) for women with a BMI<25 kg/m2 and 2.0 (95% CI 1.3-3.0) for women with BMI>or=25 kg/m2. CONCLUSIONS: Adult weight gain, particularly during the peri-menopausal period, plays a significant role in the development of endometrial cancer risk.