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The climate history of the Alxa desert of northwestern China must be sought both in recent instrumental records (dating from 1960) and in high‐resolution proxy data. Climate proxies are scarce in desert areas; however, long‐lived desert shrubs can offer one such proxy. We have used shrub‐ring data from Zygophyllum xanthoxylum, collected in the central Alxa desert, to reconstruct the Self‐calibrating Palmer Drought Severity Index (scPDSI) for the period 1880–2015. The data covers the May–July growth season. When we compared the history constructed from the shrub‐ring data with the instrumental data collected 1960–2015, we found that the reconstructed history explained 41% of the variance in scPDSI data (40% after adjusting for loss of degrees of freedom). The reconstructed history shows that this region has experienced six persistent droughts and four seasons wetter than usual during the period under study. Of note is a severe drought event in 1920s that affected much of northern China (as noted in contemporary documents). The droughts and wet seasons identified in our reconstruction are consistent with reports from other researchers who have studied the climate history or the region. Our study suggests that it is feasible to reconstruct climate history using shrub‐ring data from long‐lived desert shrubs. [ABSTRACT FROM AUTHOR]

t is of great significance for gully prevention and management to identify the potential sediment source of debris flow. Debris flow in a gully always originates from tributaries that have different gravity potential energies and sediment condition. In this study, tributaries of the Jiangjia Gully (JJG) in Yunnan province, China, are taken as the study area to determine the possible sediment sources of debris flow. It was found that tributaries with a high evolution index (EI, the integral of the hypsometric curve) always had high gravity potential energy, which favors the occurrence of landslide activity. Furthermore, the relationship between sediment distribution, gravity potential energy, and EI is compared, respectively. The results showed that the EI had a greater influence on the occurrence of landslides, and sediments were concentrated in tributaries with EI between 0.5 and 0.6. Accordingly, tributaries with EI > 0.5 were identified as the sediment sources of debris flow. In addition, the shape of a tributary was related to EI and can reflect the condition of water and sediment storage. [ABSTRACT FROM AUTHOR]

Landslide susceptibility assessment is of great significance for the disaster prediction and prevention. At present, most studies used statistical methods by the influence factors of landslide distribution, or based on physical models to determine the assessment result, the research of these methods was mainly focused on the gully scale. At the same time, these methods did not focus on the specific principle of material storage. In this paper, the surface erosion index, being the integral of the hypsometric curve, is adopted to explore the landslides distribution characteristic in different tributaries of the gully. Firstly, 81 tributaries of JJG are taken from DEM with 10 m grid cells, and the hypsometric curves are used to characterize their evolution stages; five stages are identified by the evolution index (EI, the integral of the hypsometric curves) and most tributaries are in relative youth stage with EI between 0.5 and 0.6. Then 906 landslides are interpreted from Quickbird satellite image of 0.61 m resolution. It is found that LD (LD = landslides number in a tributary/ the tributary area) increases exponentially with EI, while LAp (LAp = landslides area in a tributary/the tributary area) fluctuates with EI, meaning that landslides are inclined to occur in tributaries with EI between 0.5 and 0.6, and thus these tributaries are the main material sources supplying for debris flows. [ABSTRACT FROM AUTHOR]

Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk. [ABSTRACT FROM AUTHOR]

Under the increasing shortage of water resources conditions, which was affected by climate changes and the human activity, the rational water management is more important especially in the inland rivers in arid regions. The stem radial activity of four Euphrates poplars ( Populus euphratica), the dominant tree species in desert riparian forests in the lower reaches of China's Heihe River basin, was measured using the point dendrometer. The daily and seasonal rhythms of stem radial activity and their relationships to environmental factors were analyzed. Generally, the diurnal radial variation followed as parabola and the cumulative stem radial growth in the growing season followed an S-shaped curve. It showed that May-August was the main period for the stem radial growth or the growth-ring formation of Euphrates poplar. And the groundwater depth was significantly correlated with stem radial growth during this period. Therefore, the annual rings of Euphrates poplar can be used to reconstruct processes that determine the regional water regime, such as river runoff and fluctuations in groundwater depth. To desert riparian forest management, suitable groundwater depths must be maintained in the spring and summer, with spring floods every 2 years, to sustain tree health and a suitable stand structure. [ABSTRACT FROM AUTHOR]

Biliary tract cancer encompasses tumors of the gallbladder, bile duct and ampulla of Vater. Gallbladder cancer is more common in women, whereas bile duct cancer is more common in men, suggesting that sex hormones may play a role in the etiology of these cancers. The intracellular action of estrogens is regulated by the estrogen receptor (ESR); thus, we examined the role of common genetic variants in ESR genes on the risk of biliary tract cancers and stones in a population-based case–control study in Shanghai, China (411 cancer cases, 895 stone cases and 786 controls). We genotyped six single-nucleotide polymorphisms (SNPs), four in ESR1 (rs2234693, rs3841686, rs2228480 and rs1801132) and two in ESR2 (rs1256049 and rs4986938). In all participants, the ESR1 rs1801132 (P325P) G allele was associated with excess risks of bile duct [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.1–2.8] and ampulla of Vater cancers (OR = 2.1, 95% CI 0.9–4.9) compared with the CC genotype. The association with bile duct cancer was apparent among men (OR = 2.8, 95% CI 1.4–5.7) but not among women (P-heterogeneity = 0.01). Also, the ESR2 rs4986938 (38 bp 3′ of STP) GG genotype was associated with a higher risk of bile duct cancer (OR = 3.3, 95% CI 1.3–8.7) compared with the AA genotype, although this estimate was based on a small number of subjects. None of the other SNPs examined was associated with biliary tract cancers or stones. False discovery rate-adjusted P-values were not significant (P > 0.1). No association was found for ESR1 haplotype based on four SNPs. These preliminary results suggest that variants in ESR genes could play a role in the etiology of biliary tract cancers, especially bile duct cancer in men. [ABSTRACT FROM PUBLISHER]

We examined the associations between 21 single nucleotide polymorphisms (SNPs) of eight lipid metabolism genes and lipid levels in a Chinese population. This study was conducted as part of a population-based study in China with 799 randomly selected healthy residents who provided fasting blood and an in-person interview. Associations between variants and mean lipid levels were examined using a test of trend and least squares mean test in a general linear model. Four SNPs were associated with lipid levels: LDLR rs1003723 was associated with total cholesterol ( P-trend = 0.002) and LDL ( P-trend = 0.01), LDLR rs6413503 was associated with total cholesterol ( P-trend = 0.05), APOB rs1367117 was associated with apoB ( P-trend = 0.02), and ABCB11 rs49550 was associated with total cholesterol ( P-trend = 0.01), triglycerides ( P-trend = 0.01), and apoA ( P-trend = 0.01). We found statistically significant effects on lipid levels for LDLR rs6413503 among those with high dairy intake, LPL rs263 among those with high allium vegetable intake, and APOE rs440446 among those with high red meat intake. We identified new associations between SNPs and lipid levels in Chinese previously found in Caucasians. These findings provide insight into the role of lipid metabolism genes, as well as the mechanisms by which these genes may be linked with disease. [ABSTRACT FROM AUTHOR]

Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.3–3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1–3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5–5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95% CI = 2.2–20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1–4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism. [ABSTRACT FROM AUTHOR]

Food loss and waste become the sever problem in the modern society. This paper studies the carbon emissions related to different circulation forms of lychee，which is a typical perishable fruit in China. First, we construct a kinetic model of lychee by using the Arrhenius equation. And then, we propose a carbon emission measurement with the unit effective carbon emission and the comprehensive carbon emission utility by using life cycle assessment. With this measurement, we measure the rate of loss and life cycle carbon emissions of four lychee's circulation scenarios, including: cold chain, room temperature, cold chain broken at the beginning and cold chain broken at the end. The results show that with the traditional carbon emission measurement, the carbon emissions generated by the cold chain circulation scenario are the highest in total carbon emissions under the four scenarios. But using the unit effective carbon emissions measurement, the total carbon emissions under the cold chain circulation situation is 34.84 % less than those of the room temperature circulation. Under the cold chain circulation scenario, the unit effective carbon emission and comprehensive carbon emission utility are 0.38 kgCO 2 /kg and 85.33 %, respectively. Improving the rate of cold chain circulation can improve the comprehensive carbon emission utility and achieve land-saving. Comparing with the cold chain circulation rate in China in today, when it increases to 95 %, the comprehensive carbon emission utility of lychee supply chain increases to 81.65 %, and the required land is reduced by 54.84 %. • The unit effective carbon emission and the comprehensive carbon emission utility are proposed. • A kinetic model of lychee is developed to measure the loss rate of lychee. • A life-cycle carbon emissions model is developed to estimate lychee carbon emissions with different scenarios. [ABSTRACT FROM AUTHOR]

Background and Aims: Gallstone disease (cholelithiasis) is a cholesterol-related metabolic disorders with strong familial predisposition. Mitochondrial DNA (mtDNA) variants accumulated during human evolution are associated with some metabolic disorders related to modified mitochondrial function. The mechanistic links between mtDNA variants and gallstone formation need further exploration., Methods: In this study, we explored the possible associations of mtDNA variants with gallstone disease by comparing 104 probands and 300 controls in a Chinese population. We constructed corresponding cybrids using trans-mitochondrial technology to investigate the underlying mechanisms of these associations. Mitochondrial respiratory chain complex activity and function and cholesterol metabolism were assessed in the trans-mitochondrial cell models., Results: Here, we found a significant association of mtDNA 827A>G with an increased risk of familial gallstone disease in a Chinese population (odds ratio [OR]: 4.5, 95% confidence interval [CI]: 2.1-9.4, P=1.2×10 -4 ). Compared with 827A cybrids (haplogroups B4a and B4c), 827G cybrids (haplogroups B4b and B4d) had impaired mitochondrial respiratory chain complex activity and function and activated JNK and AMPK signaling pathways. Additionally, the 827G cybrids showed disturbances in cholesterol transport and accelerated development of gallstones. Specifically, cholesterol transport through the transporter ABCG5/8 was increased via activation of the AMPK signaling pathway in 827G cybrids., Conclusions: Our findings reveal that mtDNA 827A>G induces aberrant mitochondrial function and abnormal cholesterol transport, resulting in increased occurrence of gallstones. The results provide an important biological basis for the clinical diagnosis and prevention of gallstone disease in the future., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In the context of global precipitation anomalies and climate warming, the evolution of fragile desert ecosystems, which account for one-third of the world's land area, will become more complex. Studies of regional climate change and ecosystem response are important components of global climate change research, especially in arid desert regions. Zygophyllum xanthoxylum and Ammopiptanthus mongolicus are two dominant but endangered shrub species in the Alxa Desert in the arid region of central Asia. Using dendrochronological methods, we studied the response of radial growth of those two species to climate factors, and the adaptability of the two shrub populations under a regional warming trend. We found that radial growth of both shrubs was mainly affected by precipitation during the growing season. In additionally, along with the decrease of precipitation and the increase of temperature from east to west of Alxa desert Plateau, the limiting effect of drought during the growing season on radial growth increased. The climate response characteristics and changes between dry and wet periods exhibited spatial and temporal heterogeneity due to micro-level geomorphological factors. Under a regional climate warming trend, individual growth and population development of the two endangered shrubs will be adversely affected. In areas where these species are naturally distributed, populations will gradually become concentrated in micro-geomorphic regions with better soil moisture conditions, such as low-lying areas in the gullies that develop in alluvial fans. This finding has important scientific significance for understanding the development of the region's dominant shrub populations and protection of these and other endangered plants in arid desert areas., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but highly fatal. Gallstones represent the major risk factor for biliary tract cancer, and share with gallbladder cancer a female predominance and an association with reproductive factors and obesity. Although estrogens have been implicated in earlier studies of gallbladder cancer, there are no data on the role of androgens. Because intracellular androgen activity is mediated through the androgen receptor (AR), we examined associations between AR CAG repeat length [(CAG)(n)] and the risk of biliary tract cancers and stones in a population-based study of 331 incident cancer cases, 837 gallstone cases, and 750 controls from Shanghai, China, where the incidence rates for biliary tract cancer are rising sharply. Men with (CAG)(n) >24 had a significant 2-fold risk of gallbladder cancer [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.07-3.73], relative to those with (CAG)(n) < or = 22. In contrast, women with (CAG)(n) >24 had reduced gallbladder cancer risk (OR, 0.69; 95% CI, 0.43-1.09) relative to those with (CAG)(n) < or = 22; P interaction sex = 0.01, which was most pronounced for women ages 68 to 74 (OR, 0.48; 95% CI, 0.25-0.93; P interaction age = 0.02). No associations were found for bile duct cancer or gallstones. Reasons for the heterogeneity of genetic effects by gender and age are unclear but may reflect an interplay between AR and the levels of androgen as well as estrogen in men and older women. Further studies are needed to confirm these findings and clarify the mechanisms involved.

Background: Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans., Aims: The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female., Methods/results: Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS., Conclusions: The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.

Objective: ACAT2 is a major cholesterol esterification enzyme specifically expressed in hepatocytes and may control the amount of hepatic free (unesterified) cholesterol available for secretion into bile or into HDL. This study aims to further elucidate physiologic roles of ACAT2 in human hepatic cholesterol metabolism., Methods and Results: Liver biopsies from 40 normolipidemic, non-obese gallstone patients including some gallstone-free patients (female/male, 18/22) were collected and analyzed for microsomal ACAT2 activity, protein and mRNA expression. Plasma HDL-cholesterol (HDL-C) was significantly higher in females than in males, while triglycerides were significantly lower. ACAT2 activity in females was significantly lower than observed in males, regardless of the presence of gallstone disease. Moreover, the activity of ACAT2 correlated negatively with plasma levels of HDL-C (r=-0.57, P<0.05) and with Apo AI (r=-0.49, P<0.05)., Conclusion: This is the first description of a gender-related difference in hepatic ACAT2 activity in normolipidemic non-obese Chinese patients suggesting a possible role for ACAT2 in the regulation of cholesterol metabolism in humans. The negative correlation between ACAT2 activity and HDL-C or Apo AI may reflect this regulation. Since ACAT2 activity generally has been found to be pro-atherogenic in animal models, the observed sex-related difference may contribute to female protection from complications of coronary heart disease (CHD).

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Gallstones, the predominant risk factor for biliary cancers, are linked with hyperlipidemia. As part of a population-based case-control study conducted in Shanghai, China, we examined the associations of serum lipid levels with biliary stones and cancers. We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile duct, and 55 ampulla of Vater), 981 biliary stone cases and 858 healthy individuals randomly selected from the population. Participants completed an in-person interview and gave overnight fasting blood samples. Participants in the highest quintile of triglycerides (>/=160 mg/dl) had a 1.4-fold risk of biliary stones (95% CI = 1.1-1.9), a 1.9-fold risk of gallbladder cancer (95% CI = 1.3-2.8), and a 4.8-fold risk of bile duct cancer (95% CI = 2.8-8.1), compared to the reference group (third quintile: 90-124 mg/dl). Participants in the lowest quintile of high-density lipoprotein (HDL) (<30 mg/dl) had a 4.2-fold risk of biliary stones (95% CI = 3.0-6.0), an 11.6-fold risk of gallbladder cancer (95% CI = 7.3-18.5), and a 16.8-fold risk of bile duct cancer (95% CI = 9.1-30.9), relative to the reference group (third quintile: 40-49 mg/dl). In addition, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A (apo A) were inversely associated with biliary stones; whereas low levels as well as high levels of total cholesterol, LDL, apo A and apolipoprotein B (apo B) were associated with excess risks of biliary tract cancers. Our findings support a role for serum lipids in gallstone development and biliary carcinogenesis., ((c) 2008 Wiley-Liss, Inc.)

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct.

Base excision repair (BER) corrects DNA damage caused by oxidative stress and chronic inflammation, putative risk factors for cancer. To understand the relationship between genetic variation in BER genes and risk of biliary tract cancer and biliary stones, we examined non-synonymous polymorphisms in three key BER genes-x-ray repair cross-complementing group 1 (XRCC1) (R194W, rs1799782; R280H, rs25489 and R399Q, rs25487), apurinic/apyrimidinic endonuclease (APEX1) (D148E, rs3136820) and 8-oxoguanine DNA glycosylase (OGG1) (S326C, rs1052133), in a population-based study of 411 biliary tract cancer cases (237 gallbladder, 127 bile duct and 47 ampulla of Vater), 891 biliary (gallbladder or bile duct) stone cases and 786 population controls conducted in Shanghai, China. Compared with subjects carrying the XRCC1 194RR genotype, those with the WW genotype had a 1.9-fold risk of bile duct cancer [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.5, P(trend) = 0.03], and compared with subjects carrying the XRCC1 280RR genotype, those with the XRCC1 280H allele had a 50% reduced risk of bile duct cancer (OR = 0.5, 95% CI = 0.3-0.9, P(trend) = 0.05). The effect of the R280H polymorphism persisted (P(trend) = 0.03), when all three XRCC1 polymorphisms were jointly considered in the model, a finding supported by the haplotype results (covariate-adjusted global permutation P = 0.03). We also found an inverse association between the APEX1 148E allele and gallbladder stones (P(trend) = 0.03), but no association for the OGG1 polymorphism. This study suggests that genetic variants in XRCC1 and APEX1 may alter susceptibility to biliary tract cancer and stones. Further studies are required to confirm the reported associations.

Background: Supersaturation of bile with cholesterol is a primary step in the formation of cholesterol gallstones. ATP binding cassette (ABC) G5 and G8 play an important role in regulating sterol absorption and secretion. To investigate a possible association between transporter gene polymorphism and gallstone formation, we examined five common polymorphisms in the ABCG5 (Q604E) and ABCG8 (D19H, Y54C, T400K, A632V) genes in patients with gallstone disease (GS)., Methods: Study subjects included 287 patients with GS and 219 gallstone free controls (GSF). Polymorphisms were determined using PCR-RFLP analysis or the Taqman MGB assay. Plasma and biliary lipid levels were measured., Results: 2 SNPs of ABCG8 gene (Y54C and T400K) showed strong linkage disequilibrium (D'=0.824, r2=0.579). Male carriers of the less frequent K allele of ABCG8 T400K had a 2.31-fold elevated risk [95% confidence interval (CI) 1.12 approximately 4.76, P=0.023] for gallstone disease compared to male with the common genotype after the adjustment for age, body mass index. Males with the K allele had lower plasma triglyceride (P=0.044) and biliary phospholipid (P=0.035) levels than TT homozygotes. No such association was found in female or other 4 SNPs., Conclusions: These findings indicate that the T400K polymorphism in ABCG8 may be associated with the incidence of gallstone disease in males.

Cancers of the biliary tract arise from the gallbladder, extrahepatic bile ducts and ampulla of Vater. Although relatively uncommon, the incidence of biliary tract cancer rose more than 100% in Shanghai, China between 1972 and 1994. Gallstones are the predominant risk factor for biliary tract cancers, with over 60% of the cancer cases having gallstones. A familial tendency to gallstones has been reported and may elevate the risk of gallbladder cancer further. As part of a large population-based case-control study of biliary tract cancers in Shanghai, China, we examined the association between a family history of gallstones and biliary tract cancers as well as biliary stones. A total of 627 biliary tract cancers (368 gallbladder, 191 bile duct, 68 ampulla of Vater), 1,037 biliary stone cases (774 gallbladder, 263 bile duct) and 959 healthy subjects randomly selected from the population were included in this study. Information on family history of gallstones among first-degree relatives (i.e., parents, siblings, offspring) was obtained through a self-reported history during in-person interviews. A family history of gallstones was associated with increased risks of biliary stones [odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.1-3.8], gallbladder cancer (OR = 2.1, 95% CI = 1.4-3.3) and bile duct cancer (OR = 1.5, 95% CI = 0.9-2.5), after adjustment for age, gender, marital status, education, smoking, alcohol drinking and body mass index. For gallbladder cancer, subjects with gallstones but without a family history of gallstones had a 21-fold risk (95% CI 14.8-30.1), while those with both gallstones and a positive family history had a 57-fold risk (95% CI 32.0-110.5). Significant risks for gallbladder cancer persisted after additional adjustment for gallstones, and when the analysis was restricted to subjects with first-degree relatives whose gallstones were treated with cholecystectomy. The significant associations with a family history of gallstones were seen for all first-degree relatives, including parents, siblings and offspring, but not spouses. This large population-based study not only supports the role of gallstones in biliary carcinogenesis but also suggests that the underlying genetic or lifestyle determinants of stones within families contribute to the risk of biliary tract cancer.

There is evidence that chronic inflammation predisposes to biliary tract cancer and that use of non-steroidal anti-inflammatory drugs (NSAIDs) is protective. Although the mechanisms by which NSAIDs lower cancer risk remain unclear, NSAIDs reduce prostaglandin production by blocking prostaglandin-endoperoxide synthase 2 (PTGS2, commonly known as COX-2), an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue. Since variants in the PTGS2 gene may modify the expression or function of its encoded enzyme to modulate the inflammatory response in the biliary tract, we examined the associations of eight PTGS2 polymorphisms (-645C-->T; Ex3 -8G-->C; IVS5 -275T-->G; IVS7 +111T-->C; Ex10 +127T-->C; Ex10 +686 --->ATTAT-->TTATA; Ex10 +837T-->C; Ex10 -90C-->T) with biliary tract cancer and stones in a population-based case-control study conducted in Shanghai, China. Genotyping was performed for 411 patients with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater), 895 patients with biliary stones (673 gallbladder, 222 bile duct), and 786 healthy individuals randomly selected from the population. Significant associations were seen only between the Ex10 +837T-->C marker and bile duct cancer risk. Relative to individuals with the TT genotype, those carrying the C allele (TC or CC genotype) had a 1.8-fold (95% confidence interval: 1.2-2.7) risk of bile duct cancer. Inferred haplotypes including this risk-conferring allele were also associated with increased bile duct cancer risk of similar magnitude. Our results suggest that a common PTGS2 variant increases bile duct cancer risk. Further investigation is needed to confirm and extend our findings in studies of biliary tract cancer that more comprehensively examine PTGS2 and other inflammation-related genes.

Objective: To explore the role of both inheritable and epidemiological factors in the pathogenesis of familial gallstone disease in pedigrees., Methods: 135 pedigrees, with 695 members aged > or = 18 (18 - 83, with a mean of 50 +/- 14), 282 males and 413 females, including 370 patients, at least one patient existing in every generation, were investigated. Inquiry was carried out to collect the personal and medical history. Physical examination and ultrasonography were conducted. Blood samples were collected to detect the total cholesterol (TCh), triglyceride (TG), high-density lipoprotein cholesterol (HDL-Ch), and apolipoprotein (Apo) A1 and ApoB. The concentration of low-density lipoprotein cholesterol (LDL-Ch) was calculated by the formula: Tch-TG/5 + HDL-Ch. The inheritable characteristics and heritability were analyzed., Results: The prevalence of gallstone disease was 53.24%, 56.66% among the females, significantly higher than that among the males (48.23%, P = 0.03). The heritability in the first-degree relatives was 138% +/- 7%, and the concordance rate of monozygotic twins was 100%. The significant risk factors were female gender (P = 0.03), body mass index (P < 0.01) and diet (P < 0.008). The history of hypertension, hyperlipidemia, and diabetes were correlated to gallstone disease (P = 0.008, < 0.008, and 0.03 respectively). Serum HDL-Ch and ApoA1 concentrations were lower in the stone group than in the non-stone group (P = 0.003 and 0.005 respectively). There were no significant differences in TCh, TG, LDL-Ch, and ApoB between the 2 groups., Conclusion: Genetic factors play a major role in the pathogenesis of familial gallstone disease, characterized by autosomal dominant inheritance. Female gender, obesity, diet, hypertension, hyperlipidemia, diabetes may be the risk factors of gallstone disease. Dyslipidemia is a characteristic of gallstone disease.

Objective: To study the characteristics of inheritance and epidemiology of gallstone disease in one pedigree., Methods: A gallbladder disease-specific questionnaire was administered to all family members to ascertain histories of cholecystectomy and other medical conditions as well as anthropometrical data. Laboratory examination and ultrasonography were performed to determine the existence of gallstone., Results: One hundred and thirteen members of four generations in the index family were enrolled in the study. The prevalence of gallstone in females (34.48%) was higher than in males (23.64%) but with no significant difference. The prevalence in the second and third generations (52%) was higher than in others (20%) (P < 0.05). The heritability and standard error showed as 86.38% +/- 46.46% in I generations. Body mass index, histories of hypertension, hyperlipidemia and blood glucose were positively related to gallstone disease (P = 0.012, < 0.01, 0.017, 0.043, respectively) in this family. Gallstone disease was not significantly related to history of diabetes, daily alcohol or diet habit. Plasma cholesterol and triglyceride levels were not correlated with gallstone disease., Conclusion: Gallstone disease presented aggregation in the family and was in accordance with the characteristics of autosomal dominant inheritance. Being female, obesity, hypertension and history of hyperlipidemia might serve as risk factors to this family.

The association of gallbladder and bile duct cancers with gallstones, cholecystitis, and cholangitis suggest that chronic inflammation contributes to the carcinogenic process. However, the effect of nonsteroidal anti-inflammatory drugs, such as aspirin, on biliary tract cancer has not been well studied. In a population-based case-control study conducted in Shanghai, China, we examined the relationship between aspirin use and the risk of biliary disease. A total of 627 patients with biliary tract cancer, including cancers of the gallbladder (n = 368), extrahepatic bile duct (n = 191), and ampulla of Vater (n = 68); 1,037 patients with biliary stones; and 958 healthy adults were included in the study. Self-reported data on aspirin use was collected from study participants by in-person interview. The prevalence of aspirin use was low, with 5.7% of the population controls being regular users. After controlling for age, sex, education, and biliary stone status, aspirin use was associated with a reduced risk of gallbladder cancer [odds ratio (OR), 0.37; 95% confidence interval (CI), 0.17-0.88]. An inverse relationship was also observed for frequency and duration of use and with younger age when starting use. In addition, there was a nonsignificant reduction in the risk of bile duct (OR, 0.48; 95% CI, 0.19-1.19) and ampullary cancers (OR, 0.22; 95% CI, 0.03-1.65) associated with aspirin use, whereas no clear association was seen with biliary stones (OR, 0.92; 95% CI, 0.59-1.44). Further studies of biliary tract cancer in other populations are needed to confirm these results and to elucidate the mechanisms that underlie the reduced risk associated with use of aspirin and possibly other nonsteroidal anti-inflammatory drugs.

Objective: To survey the status of diagnosis and treatment of biliary tract cancer in Shanghai., Methods: A clinical epidemiology investigation was carried out on 658 new cases of biliary duct cancers aged 35-74, that registered between June 1997 and May 2001 in urban Shanghai. Clinical findings were collected in 390 gallbladder cancer, 195 bile duct cancer and 73 ampullary cancer., Results: Biliary tract cancers mainly occurred in elderly patients. Ratio of males to female was 1:2.61 in gallbladder cancer, while bile duct cancer and ampullary cancer were slightly more common in men. Association with gallstones was 68.5%, 43.1% and 22.4% for gallbladder cancer, bile duct cancer and ampullary cancer, respectively. Diagnostic accuracy rate of B-ultrasonography was 63.1% in gallbladder cancer. Incidental gallbladder cancer accounted for 20%, while stage IVA and IVB patients reached up to 43.6%. Misdiagnosis rate was still high in bile duct cancer and ampullary cancer, it was 19.1% and 47.1% respectively. In addition, most patients presented jaundice at diagnosis. 69 cases (18.2%) of gallbladder cancer, 50 cases (25.6%) of bile duct cancer and 54 cases (74%) of ampullary cancer underwent radical resection, the 1-, 3- and 5-year survival rates were 58.5%, 42.8% and 40.7%, 58%, 28.3% and 11.1%, 81.5%, 39.2% and 26.9%, respectively. 79 patients with bile duct cancer underwent palliative drainage, and most cases died within 1 year. Metal endo-prostheses or plastic stents were placed into the biliary tract in 38 patients. The median survival was about 7 months., Conclusions: It is difficult to make early diagnosis of biliary tract cancers. Standardization of the operation for gallbladder cancer must be respected. Surgical exploration should be undertaken when a bile duct cancer is suspected and there are no contraindications to surgery. Pancreatoduodenectomy should be recommended for ampullary cancer.