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Only two genome-wide association studies (GWAS) have been conducted to date to identify potential markers for total mortality after diagnosis of breast cancer. Here, we report the identification of two single-nucleotide polymorphisms (SNP) associated with total mortality from a two-stage GWAS conducted among 6,110 Shanghai-resident Chinese women with tumor–node–metastasis (TNM) stage I to IV breast cancer. The discovery stage included 1,950 patients and evaluated 613,031 common SNPs. The top 49 associations were evaluated in an independent replication stage of 4,160 Shanghai patients with breast cancer. A consistent and highly significant association with total mortality was documented for SNPs rs3784099 and rs9934948. SNP rs3784099, located in the RAD51L1 gene, was associated with total morality in both the discovery stage (P = 1.44 × 10−8) and replication stage (P = 0.06; P-combined = 1.17 × 10−7). Adjusted HRs for total mortality were 1.41 [95% confidence interval (CI), 1.18–1.68] for the AG genotype and 2.64 (95% CI, 1.74–4.03) for the AA genotype, when compared with the GG genotype. The variant C allele of rs9934948, located on chromosome 16, was associated with a similarly elevated risk of total mortality (P-combined = 5.75 × 10−6). We also observed this association among 1,145 patients with breast cancer of European ancestry from the Nurses’ Health Study (NHS; P = 0.006); the association was highly significant in a combined analysis of NHS and Chinese data (P = 1.39 × 10−7). Similar associations were observed for these two SNPs with breast cancer–specific mortality. This study provides strong evidence suggesting that the RAD51L1 gene and a chromosome 16 locus influence breast cancer prognosis. Cancer Res; 72(5); 1182–9. ©2012 AACR.

The sustainable development of resource-based cities is vital to China's high-quality development. Based on the support-pressure framework, this study simplifies the city system into an economy-society subsystem (ESS) and a resource-environment subsystem (RES), and measures the economy social developmental level (ESDL) and resource environmental carrying capacity (RECC) of China's 116 resource-based cities using the improved entropy-TOPSIS model. Then, it applies the coupling coordination degree (CCD) and relative development models to explore their coupling coordination relationships and relative developmental types. The results are as follows. (1) The ESDL and RECC of China's resource-based cities have improved significantly, and there is a large divergence between cities in different regions, development stages, and dominant resource types. (2) The CCD between the ESDL and RECC of China's resource-based cities is still not ideal, and no city qualifies for the high coordination category. (3) Overall, the RECC lags behind the ESDL, and the cities with a lagging ESDL are concentrated in the western and northeastern regions. Based on these conclusions, three specific suggestions are put forth. This study may provide a scientific reference for the Chinese government to formulate a sustainable development plan for resource-based cities. Integr Environ Assess Manag 2022;18:770-783. © 2021 SETAC.

Cases of extrahepatic bile duct carcinoma are mostly adenocarcinomas and extrahepatic bile duct squamous cell carcinomas are rare. We report here a case of choledochal squamous cell carcinoma in a young woman who underwent surgery and chemotherapy. The woman presented with abdominal discomfort. A physical examination showed tenderness in the upper abdomen. Laboratory tests showed elevated direct bilirubin, total bilirubin, and C-reactive protein levels. Abdominal computed tomography and magnetic resonance imaging showed a cystic-solid mixed soft tissue mass in the common bile duct. Pain symptoms in the patient were not relieved and surgical treatment was performed. Postoperative pathological results showed a choledochal cyst complicated by squamous cell carcinoma. The patient was treated by biliary intestinal anastomosis followed by chemotherapy. However, the patient developed liver metastasis and recurrence at a 6-month follow-up. Primary congenital bile duct cysts with squamous cell carcinoma are extremely rare. Surgical resection is the main treatment option for choledochal squamous cell carcinoma. Postoperative chemoradiotherapy can be used, but the efficacy is poor and chemotherapy does not significantly prolong the patient’s survival.

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.

OBJECTIVE To investigate the relationship between BMI．WHR and billary tract cancers(CBT)． METHODS A population-based case—controI study was conducted in urban Shanghai fromJune 1,1997to May 31,2001 involving interviews with 627 new cases of biliary tract cancers aged 35tO 74 years and 959 frequency-matched population controls bygender and age in five-year groups．All subjects wereinterviewedin person by trained interviewers using a structured questionnaire．An unconditional logistic regression was performed to calculate adjusted odds ratios(ORs) and 95％ confidence intervals(CIs)． RESULTS Obesity was associated with an increased risk of gallbladder cancer across adulthood at ages 20-29 and 30-39 in females．Compared with subjects inthelowest quartile of WHR，ORs for the highestquartile and P for trend for cancers of gallbladder and extrahepatic bile duct both reached significant levels among males andfemales． CONCLUSION Our observationsin urban Shanghai suggested that obesity in early adult life may contribute to the risk of gallbladder cancer，and increasedWHR maysubstantially elevatedrisk of cancers of the gallbladder and extrahepatic bile duct．

Cyclin D1 (CCND1) is a key cell cycle regulatory protein that governs cell cycle progression from the G1 to S phase. A common polymorphism (A870G) in exon 4 of the CCND1 gene produces an alternate transcript (transcript-b) that preferentially encodes a protein with enhanced cell transformation activity and possible prolonged half-life. We evaluated the association of CCND1 A870G polymorphism with breast cancer risk and survival in 1,130 breast cancer cases and 1,196 controls who participated in the Shanghai Breast Cancer Study. Approximately 81% of cases and 79% of controls carried the A allele at A870G of the CCND1 gene [odds ratio, 1.1; 95% confidence interval (95% CI), 0.9-1.4]. As lightly stronger but nonsignificant association was found for the A allele among younger women (odds ratio, 1.3; 95% CI, 0.9-1.8). However, this polymorphism seems to modify the effect of hormonal exposures on postmenopausal breast cancer, as the positive associations of postmenopausal breast cancer with body mass index (Pfor interaction = 0.02) and waist-to-hip ratios (P for interaction < 0.03; all Ps are two sided) were only observed among women who carry the A allele at A870G of the CCND1 gene. Following up with this cohort of patients for an average of 4.84 years, we found that the CCND1 A870G polymorphism was inversely associated with overall and disease-free survival, particularly among women with late stage or estrogen/progesterone receptor-negative breast cancer. The adjusted hazard ratios for disease-free survival associated with GA and AA genotypes were 0.94 (95% CI, 0.49-1.82) and 0.41 (95% CI, 0.19-0.91) for tumor-node-metastasis stage III to IV breast cancer, and 0.35 (95% CI, 0.15-0.80) and 0.32 (95% CI, 0.13-0.79) for estrogen/progesterone receptor-negative breast cancer. This study suggests that CCND1 A870G polymorphism may modify the postmenopausal breast cancer risk associated with hormonal exposure and predict survival after breast cancer diagnosis.

Altered motility of the gallbladder can result in gallstone and cholecystitis, which are important risk factors for biliary tract cancer. Motilin (MLN) and somatostatin (SST) are known important modulators of gallbladder motility. To determine whether genetic variants in motilin, somatostatin, and their receptor genes are associated with the risk of biliary tract cancers and stones, nine tag-SNPs were determined in 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 a population-based case–control study in Shanghai, China. We found that subjects with the MLNR rs9568169 AA genotype and SSTR5 rs169068 CC genotype were significantly associated with risk of extrahepatic bile duct cancer (OR = 0.49, 95% CI: 0.27–0.89; OR = 2.40, 95% CI: 1.13–5.13) compared to the major genotypes. MLN rs2281820 CT and rs3793079 AT genotypes had significantly increased risks of gallstones (OR = 1.52, 95% CI: 1.06–2.18; OR = 1.64, 95% CI: 1.20–2.25) compared to TT genotypes. Besides, haplotype analysis showed that MLN T-T-T haplotype (rs2281820–rs3793079–rs2281819) had a non-significantly elevated risk of gallstone (OR = 1.30, 95% CI: 0.91–1.86) compared with C-A-A haplotype. To the best of our knowledge, this is the first study to report an association between genetic polymorphisms in MLN, MLNR and their receptor genes and risk of biliary tract cancers and stones., Highlights • We conduct a population-based case–control study of biliary tract diseases in China. • We examine nine TagSNPs in gallbladder motility genes in this study. • MLNR rs9568169 and SSTR5 rs169068 are related to extrahepatic bile duct cancer risk. • MLN rs2281820 and rs3793079 are associated with gallstone risk.

Purpose: Biliary tract cancer is an uncommon malignancy with a poor survival rate. We evaluated p16 gene alteration as a prognostic marker for this disease. Experimental Design: We studied p16 gene alterations by sequencing, methylation, and loss of heterozygosity of chromosome 9p in 118 biliary tract carcinomas, including 68 gallbladder cancers, 33 extrahepatic bile duct cancers, and 17 ampullary cancers. Survival was evaluated in 57 patients with gallbladder carcinomas, 27 with bile duct carcinomas, and 16 with ampullary carcinomas with and without somatic p16 alterations detected by two different methods. Results: p16 gene alterations including silent mutations were present in 61.8% gallbladder cancers, 54.5% bile duct cancers, and 70.6% ampullary cancers. p16 gene nonsilent mutations, p16 methylation, and loss of chromosome 9p21-22 that targets p14, p15, and p16 genes were present in 13 of 53 (24.5%), 8 of 54 (14.8%), and 32 of 44 (72.7%) gallbladder tumors; 5 of 25 (20.0%), 5 of 31 (16.1%), and 12 of 21 (57.1%) bile duct tumors; and 3 of 13 (23.1%), 6 of 15 (40.0%), and 8 of 16 (50.0%) ampullary tumors, respectively. The mean survival of patients with gallbladder cancers without p16 alterations was 21.5 ± 14.8 months compared with 12.1 ± 11.4 months for patients with p16 alterations (P = 0.02). Conclusions: Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma, with more favorable survival rates associated with carcinomas lacking p16 gene alterations.

To study the relationship between obesity at different ages and the risk of endometrial cancer in urban Shanghai, China.In a population-based case-control study conducted in urban Shanghai, in-person interviews and anthropometric measurements were completed for 497 women at age 30 to 69 and an equal number of controls frequency-matched to cases on age distribution. All cases were newly diagnosed with endometrial cancer from January 1, 1997 to June 30, 2000. Unconditional logistic regression model was employed to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the obesity at different ages.After adjustment for some potential confounding variables, neither adolescent height nor weight was significantly related to endometrial cancer. Obesity in adulthood, except around 20 years old, was associated with elevated risks, with odds ratios for the highest versus lowest quartile of body mass index (BMI) being 1.5 (95% CI: 1.0 - 2.1), 1.7 (95% CI: 1.2 - 2.4), 1.9 (95% CI: 1.3 - 2.8) and 1.7 (95% CI: 1.0 - 2.7) at ages 30, 40, 50 and 60, respectively. Weight gain of more than 7.5 kg at different 10-year intervals in adulthood were associated with increased risk of endometrial cancer, whereas only weight gain more than 15% of initial weight from 40 to 50 years old significantly related to the risk. Only weight loss from ages 20 to 30 was inversely associated with endometrial cancer risk (OR = 0.4, 95% CI: 0.2 - 0.8). Current body weight, BMI and waist-to-hip ratio (WHR) were independent risk factors to endometrial cancer while standing height and sitting-to-standing height ratio were unrelated to the risk of endometrial cancer.Results indicated that adolescent obesity was unrelated to endometrial cancer. General obesity in adulthood, as well as body fat distribution, were associated with the risk of endometrial cancer independently. Weight changes before and after age 30 had different effects on the risk of endometrial cancer.

Although the majority of ecological and experimental studies have suggested a potential role of phytoestrogens in breast cancer prevention, findings from epidemiological studies have been inconsistent. Part of the inconsistencies may be attributable to the difficulty in measuring intake levels of phytoestrogens. Overnight urine samples from 250 incident breast cancer cases and their individually matched controls were analyzed for urinary excretion rates of isoflavonoids, mammalian lignans, and citrus flavonoids. The study subjects were a subset of the participants in the Shanghai Breast Cancer Study, a large population-based case-control study conducted in Shanghai from 1996-1998. To minimize potential influence of treatment on the exposure of interest, urine samples from breast cancer cases were collected before cancer therapy. Urinary excretion of total isoflavonoids and mammalian lignans was substantially lower in breast cancer cases than in controls. The median excretion rate of total isoflavonoids was 13.97 nmol/mg creatinine in cases and 23.09 in controls (P = 0.01), and the median excretion rate of total lignans was 1.77 in cases and 4.16 in controls (P0.01). The risk of breast cancer was reduced with increasing excretion of total isoflavonoids (P for trend, 0.04) and total lignans (P for trend,0.01), with adjusted odds ratios of 0.62 (95% confidence interval, 0.39-0.99) and 0.40 (95% confidence interval, 0.24-0.64) observed for the highest versus the lowest tertile of total isoflavonoid and lignan excretion, respectively. The adjusted odds ratio was 0.28 (95% confidence interval, 0.15-0.50) for women who had a high excretion rate of both total lignans and isoflavonoids compared with those with a low excretion of both groups of phytoestrogens. No association was observed with citrus flavonoids. The results from this study suggest that high intake of certain phytoestrogens may reduce the risk of breast cancer.

Les changements de birefringence sont plus faibles dans des cristaux LiNbO 3 :Mg+Ti que dans LiNbO 3 :Mg