Association between Helicobacter bilis in Bile and Biliary Tract Malignancies: H. bilis in Bile from Japanese and Thai Patients with Benign and Malignant Diseases in the Biliary Tract

Japan and Thailand have high incidences of bile duct carcinoma and gallstones. The presence of Helicobacter bilis ( H. bilis ) detected by polymerase chain reaction (PCR) and 16S rRNA analysis in bile samples from Chileans with chronic cholecystitis was reported. The association between H. bilis in bile and biliary tract malignancies has not been investigated, and therefore the aim of this study is to determine whether malignant diseases of the biliary tract are associated with the presence of H. bilis in bile samples obtained from two high-risk populations. Bile samples from 45 Japanese and 40 Thai patients were subjected to PCR analysis using H. bilis -specific primers, and six of the H. bilis amplicons were sequenced. Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and/or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non-biliary diseases among the Japanese ( P <0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and/or cholecystitis were 6.50 (95%CI 1.09–38.63) in the Japanese and 5.86 (1.31–26.33) in the Thai patients. In conclusion, H. bilis infection in bile was associated with biliary tract and gallbladder cancers in two high risk populations, Japanese and Thai.     

Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract.

Japan and Thailand have high incidences of bile duct carcinoma and gallstones. The presence of Helicobacter bilis (H. bilis) detected by polymerase chain reaction (PCR) and 16S rRNA analysis in bile samples from Chileans with chronic cholecystitis was reported. The association between H. bilis in bile and biliary tract malignancies has not been investigated, and therefore the aim of this study is to determine whether malignant diseases of the biliary tract are associated with the presence of H. bilis in bile samples obtained from two high-risk populations. Bile samples from 45 Japanese and 40 Thai patients were subjected to PCR analysis using H. bilis-specific primers, and six of the H. bilis amplicons were sequenced. Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and / or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non-biliary diseases among the Japanese (P < 0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and / or cholecystitis were 6.50 (95%CI 1.09 - 38.63) in the Japanese and 5.86 (1.31 - 26.33) in the Thai patients. In conclusion, H. bilis infection in bile was associated with biliary tract and gallbladder cancers in two high risk populations, Japanese and Thai.     

Fruit and Vegetable Intake and Stomach Cancer among Male Adults: A Case-Control Study in Northern Viet Nam

Objective: This study investigated the association between fruit and vegetable intake and stomach cancer, with considering the impacts of Helicobacter pylori (H. pylori) infection and tobacco smoking. Methods: A case-control study featuring 80 male incident stomach-cancer cases and 126 male controls was conducted in a general hospital in Viet Nam. A semi-quantitative food frequency and demographic lifestyle questionnaire were used; and venous blood samples were collected to determine H. pylori status by IgG ELISA. The respective associations between fruit and vegetable intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. Results: Fruit intake and stomach cancer showed a weak inverse association when this became non-significant after adjusting for H. pylori infection (OR = 0.50, 95%CI: 0.22–1.12, p trend = 0.094). Stratifying by H. pylori status returned a negative trend for fruit intake and stomach cancer among H. pylori-negative participants (OR = 0.21, 95%CI: 0.06–0.69, p trend = 0.010), but no significant interaction for H. pylori-positive participants (OR = 0.76, 95%CI: 0.21–2.68, p trend = 0.670). Vegetable intake and stomach cancer showed no association, regardless of H. pylori status. Compared to ever-smokers with low intake, never-smokers with high vegetable (OR = 0.25, 95% CI: 0.06–0.95) and fruit intake (OR = 0.20, 95%CI: 0.06–0.65) showed the lowest odds of stomach cancer. Conclusions: Fruit, but not vegetable, intake showed a weak inverse association with stomach cancer. H. pylori infection and tobacco-smoking status may influence the protective effects of fruit and vegetable intake on stomach cancer.     

Family history of gallstones and the risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China

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.     

Biliary tract cancer and stones in relation to chronic liver conditions: A population-based study in Shanghai, China

Biliary tract cancers are relatively rare but fatal tumors. Apart from a close link with gallstones and cholangitis, risk factors for biliary tract cancer are obscure. Chronic liver conditions, including liver cirrhosis, have been linked to a higher risk of biliary tract cancer. In a population-based case-control study conducted in Shanghai, China, we investigated the relationships of a history of chronic hepatitis and liver cirrhosis as well as a family history of liver cancer with biliary tract cancer risk. The study included 627 patients with biliary tract cancers (368 gallbladder, 191 bile duct and 68 ampulla of Vater), 1,037 patients with biliary stones (774 gallbladder stones and 263 bile duct stones) and 959 healthy subjects randomly selected from the population. Bile duct cancer was associated with self-reports of chronic liver conditions, including a history of chronic hepatitis (OR = 2.0, 95% CI 0.9-4.4), liver cirrhosis (OR = 4.7, 95% CI 1.9-11.7) and a family history of primary liver cancer (OR = 2.0, 95% CI 1.0-3.9). The excess risk persisted after adjustment for gallstones and were more pronounced among subjects without gallstones (OR = 5.0, 95% CI 1.3-20.0 and OR = 4.9, 95% 2.0-12.2, respectively). History of liver conditions was also associated with an excess of biliary stones (OR = 1.9, 95% CI 1.2-3.0). No association was found for cancers of the gallbladder and ampulla of Vater. A history of chronic hepatitis and cirrhosis may be risk factors for extraheptic bile duct cancer. Given that chronic infection with hepatitis B virus (HBV) is the most common cause of liver disease in China, serologic markers of HBV need to be measured in future studies to examine the link between HBV and bile duct cancer.     

Trans-Lycopene and β-Cryptoxanthin Intake and Stomach Cancer in Vietnamese Men: A Pilot Case-Control Study

Objective: To examine the association between dietary intake of Trans-Lycopene and β-Cryptoxanthin and stomach cancer in Vietnamese men. Methods: A case-control study including 80 male incident stomach cancer cases and 146 male controls was performed in a general hospital in Viet Nam. A validated semi-quantitative food frequency (SQFFQ) and demographic lifestyle questionnaire were designed, and venous blood samples were collected to determine H. pylori status by IgG ELISA. Nutrient intake was converted using the data of SQFFQ and the Nutritive Composition Table of Vietnamese Foods, updated in 2019. The respective associations between Trans-Lycopene and β-Cryptoxanthin intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. Results: Both Trans-Lycopene and β-Cryptoxanthin intake and stomach cancer showed a significantly inverse association, tertile-3 versus tertile-1, (OR = 0.15, 95%CI: 0.06–0.35, p trend = 0.00) and (OR = 0.34, 95%CI: 0.14–0.79, p trend = 0.02, respectively). For Trans-Lycopene intake stratifying by H. pylori status remained the benefit effect against stomach cancer among H. pylori-negative participants (OR = 0.15, 95%CI: 0.03–0.69, p trend = 0.02) and H. pylori-positive participants (OR = 0.13, 95%CI: 0.04–0.42, p trend = 0.00). Conclusions: Both Trans-Lycopene and β-Cryptoxanthin intake showed a strong protective effect against stomach cancer. The findings suggest that these two types of fat-soluble micronutrients would be considered as an anti-cancer therapy for both primary and secondary prevention.     

Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone: a population-based case-control study in Shanghai, China

Biliary tract cancer, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, is a rare but highly fatal malignancy. Obesity and gallstones, both related to insulin resistance, are linked to an elevated risk of biliary cancer. The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs), expressed in adipose tissue, play a key role in the regulation of obesity-related insulin sensitivity, thus genetic variants of these two receptor genes may be related to biliary cancer and stones. We examined the associations of seven single-nucleotide polymorphisms in the PPAR-gamma, PPAR-delta, RXR-alpha, RXR-beta and INS genes with biliary cancer and stones in a population-based case-control study in Shanghai, China. We included 237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater cancer cases, 895 stone cases and 786 population controls. Relative to individuals with the RXR-beta C51T (rs2076310) CC genotype, those having the TT genotype had a 1.6-fold risk for bile duct cancer [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 0.99-2.84], with a more pronounced association among men (OR = 2.30; 95% CI = 1.14-4.65; P interaction = 0.07). This marker was also associated with a higher risk of gallstones among subjects with a higher body mass index (BMI) (>or=23 kg/m(2)) (OR = 1.80; 95% CI = 1.09-2.94), although the interaction with BMI was not statistically significant (P interaction = 0.28). No association was found between other variants and biliary cancers and stones. Results from this population-based study suggest that certain genetic variants involved in the regulation of obesity-related insulin sensitivity may increase susceptibility to bile duct cancer and gallstones.     

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.     

Gallstones and the risk of biliary tract cancer: a population-based study in China

We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0-33.4), 8.0 (95% CI 5.6-11.4), and 4.2 (95% CI 2.5-7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9-59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P<0.001). Gallstone weight in gallbladder cancer was significantly higher than in gallstone patients (4.9 vs 2.8 grams; P=0.001). We estimate that in Shanghai 80% (95% CI 75-84%), 59% (56-61%), and 41% (29-59%) of gallbladder, bile duct, and ampulla of Vater cancers, respectively, could be attributed to gallstones.     

CYP17 MspA1 polymorphism and risk of biliary tract cancers and gallstones: a population-based study in Shanghai, China

Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile duct and ampulla of Vater, are rare but highly fatal malignancies. Other than gallstones, little is known about the risk factors for biliary tract cancers. Endogenous estrogens are thought to play a role in the etiology of gallstones and gallbladder cancer, since both conditions predominate in females and are associated with parity and obesity. In view of reports linking the CYP17 MspA1 polymorphism to high circulating levels of estrogens and a predisposition to other hormonally related cancers, we examined the relationship between CYP17 MspA1 variants and risk of biliary disease in a population-based case-control study in Shanghai. The study included 446 cancer cases (254 gallbladder, 139 extrahepatic bile duct, 53 ampullary cancers), 929 biliary stone cases (691 gallbladder, 238 bile duct) and 818 population controls. Genomic DNA from peripheral blood lymphocytes was used for genotyping. Relative to those with the A2/A2 genotype, A1 carriers (A1/A1 and A1/A2 genotypes) had an increased risk of gallbladder cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-2.1). In addition, women with the A1 allele and high parity (> or =3) had a 3-fold risk of gallbladder cancer (OR = 3.3, 95% CI = 1.6-6.9), compared to those with the A2/A2 genotype and lower parity, with the highest risk seen for those also having biliary stones (OR = 4.6, 95% CI = 1.8-11.7, P(interaction) = 0.04). The A1 allele was not associated with a higher risk of gallstones except among those with body mass index (BMI) greater than 25 kg/m2 (OR = 3.1, 95% CI = 2.0-4.8, P(interaction) = 0.02) and among those with a history of diabetes (OR = 2.5, 95% CI = 1.4-4.3, P interaction = 0.09). No clear relation was seen between the CYP17 polymorphism and cancers of the bile duct or ampulla of Vater. The association of the CYP17 MspA1 polymorphism with an increased risk of gallbladder cancer, as well as biliary stones among overweight and diabetic individuals, suggests an interplay between genetic and hormonal risk factors in gallbladder disease.     

DNA修复基因XPD单核苷酸多态与胆道癌遗传易感性

目的:研究核苷酸切除修复基因XPDAsp312Asn位点以及Lys751Gln位点多态与上海市区人群胆道癌风险的关系。方法:采用全人群病例-对照研究的方法运用PCR-RFLP对443名胆道癌患者和448名正常对照进行基因型分析。比较各基因型在病例与对照中分布频率的差异,并探讨基因、环境因素在胆道癌发生过程中的作用。结果:与携带XPD 751Lys/Lys基因型者比较,携带Gln/Gln基因型者罹患胆道癌的风险显著增加(校正OR=6.32;95%CI=1.16~34.53)。按解剖部位分析显示,风险增高只限于壶腹部癌(校正的OR=13.17;95%CI=1.71~101.38)。携带312Asn/Asn基因型者罹患壶腹部癌的风险显著高于携带Asp/Asp基因型者(校正后OR=20.09;95%CI=1.13~357.99)。在不伴有胆石症人群中,751Gln/Gln基因型携带者罹患胆道癌风险增加(校正后OR=5.92;95%CI=1.05~33.36),提示在不伴有胆石症人群中,遗传因素可能是发生胆道癌的影响因素。而在饮酒人群中携带751Lys/Gln或Gln/Gln基因型者较携带Lys/Lys基因型者患胆道癌风险增加约3倍。结论:XPD 312Asn等位基因以及751Gln等位基因可能是中国上海地区人群胆道癌尤其是壶腹部癌风险的遗传易感因素。     

Lifestyle and Anti-Helicobacter pylori Immunoglobulin G Antibody among Outpatients

Since eradication of Helicobacter pylori (H. pylori) is thought to be a preventive measure against stomach cancer, several studies have examined factors associated with the infection. This paper reports the association of the infection with lifestyle factors observed in a hospital-based case-control study. Cases were 140 anti-H. pylori IgG antibody-positive outpatients (75 males and 65 females). Controls were 52 antibody-negative outpatients (22 males and 30 females). Both groups had undergone gastroscopy at Aichi Cancer Center Hospital between February 1995 and February 1997, and lifestyle data collected on the first visit were linked to calculate odds ratios. A strong association was observed with smoking among males; age-adjusted odds ratio (OR)=7.85, 95% confidence interval (CI), 2.03–30.4. Rice breakfast (OR=3.74; 95%CI, 1.30–10.8) and soybean paste soup (every day vs. occasionally, OR=5.24; 95%CI, 1.80–15.2) were also associated with antibody positivity in males, but not in females. In females, pickled Chinese cabbage (≥l/week vs. ≥3/month, OR=2.82; 95%CI, 1.06–7.48) and lettuce (≥ I/week vs. ≤3/month, OR=2.90; 95%CI, 1.09 7.76) were significantly associated with positivity. Multivariate analysis gave similar estimates for the above factors. Although the association between smoking and H. pylori infection has not been detected in past studies of a general population, except one recent one, this study on outpatients suggested a possible association. Smoking may work as a cofactor disturbing incidental eradication of H. pylori by antibacterial agents administered for other reasons.     

Variants of DNA repair genes and the risk of biliary tract cancers and stones: a population-based study in china

Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic ducts, and ampulla of Vater, are relatively rare tumors with a high fatality rate. Other than a close link with gallstones, the etiology of biliary tract cancers is poorly understood. We conducted a population-based case-control study in Shanghai, China, to examine whether genetic variants in several DNA repair genes are associated with biliary tract cancers or biliary stones. Genomic DNA from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and 47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects randomly selected from the Shanghai population were genotyped for putative functional single nucleotide polymorphisms in four DNA repair genes (MGMT, RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined, only one (MGMT EX5-25C>T, rs12917) was associated with biliary tract cancer. Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5-25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.41-0.97; P = 0.02] and nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was not associated with biliary stones, and the other markers examined were not significantly associated with either biliary tract cancers or stones. Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required.     

Development and clinical pathology of carcinoma of the gallbladder and extrahepatic bile duct

We reported the causes of cancer development and clinical pathology of the gallbladder and extrahepatic bile duct carcinoma. Gallstone, secondary bile acid, and congenital malunion between the bile duct and the pancreatic duct are considered as causes of intestinal metaplasia of the mucosa of the biliary tract. The intestinal metaplasia has closely relationship with development of dysplasia and carcinoma. We treated 101 patients with gallbladder carcinoma and 85 patients with bile duct carcinoma. Sex ratios of the patients with gallbladder carcinoma and bile duct carcinoma were 1:1.8 and 1.7:1. Fifty-one of 101 patients with gallbladder carcinoma had gallstones, and 17 of them had congenital malunion between the bile duct and the pancreatic duct. In four of 23 patients with gallbladder carcinoma and 10 of 64 patients with bile duct carcinoma, superficial cancer spread was seen and it was very important for surgical operation clinically.     

Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China

To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.     

Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case-control study in China

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.     

Role of Plasticity Region Genes and cagE gene of cagPAI of Helicobacter pylori in Development of Gastrointestinal (GI) Diseases

Background: Helicobacter pylori is a Gram-negative, micro aerophilic bacterium in the human stomach that is associated with the development of gastrointestinal ailments such as peptic ulcer (PU) and gastric cancer (GC). In the present study, plasticity region genes (jhp0940, jhp0945 and jhp0947) and and cagE gene of cagPAI were assessed independently and in combination for their ability to predict clinical consequences. Materials and Methods: A total of 211 strains which were isolated from patients with different gastrointestinal diseases (114 with non-atrophic gastritis, 59 with PU, and 38 with GC) were genotyped by PCR and sequencing. Data were collected and analyzed using SPSS software version 19. Logistic regression models were applied to determine relationships between the plasticity region genes and cagE of H.pylori and clinical status. Results: The cagE gene (71.1%) had the highest frequency and jhp0945 (13.7%) was the least abundant among the genes examined. The jhp0940 gene was significantly associated with GC (P = 0.0007), but not PU. On multiple logistic regression analysis, adjusted for both age and sex, the jhp0940 genotype was significantly associated with GC (odds ratio, OR = 2.8, 95%CI = 1.1–7.0; P = 0.027). The jhp0940+/ jhp0945+/ jhp0947+genotype was also linked to an increased risk of GC (OR = 50.4, 95%CI = 5.1–500.0; P = 0.0008) while no genotype correlation was found with PU in Iran (P > 0.05). Conclusions: Given the high frequency of cagE, this gene could be a suitable marker for the presence of cagPAI in Iranian strains. The jhp0940 genotype could also be a strong predictor of GC in Iran.     

Aspirin use and risk of biliary tract cancer: a population-based study in Shanghai, China.

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.     

Trans-Lycopene and β-Cryptoxanthin Intake and Stomach Cancer in Vietnamese Men: A Pilot Case-Control Study

Objective:To examine the association between dietary intake of Trans-Lycopene and β-Cryptoxanthin and stomach cancer in Vietnamese men. Methods:A case-control study including 80 male incident stomach cancer cases and 146 male controls was performed in a general hospital in Viet Nam. A validated semi-quantitative food frequency (SQFFQ) and demographic lifestyle questionnaire were designed, and venous blood samples were collected to determine H. pylori status by IgG ELISA. Nutrient intake was converted using the data of SQFFQ and the Nutritive Composition Table of Vietnamese Foods, updated in 2019. The respective associations between Trans-Lycopene and β-Cryptoxanthin intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. Results:Both Trans-Lycopene and β-Cryptoxanthin intake and stomach cancer showed a significantly inverse association, tertile-3 versus tertile-1, (OR = 0.15, 95%CI: 0.06–0.35, p trend = 0.00) and (OR = 0.34, 95%CI: 0.14–0.79, p trend = 0.02, respectively). For Trans-Lycopene intake stratifying by H. pylori status remained the benefit effect against stomach cancer among H. pylori-negative participants (OR = 0.15, 95%CI: 0.03–0.69, p trend = 0.02) and H. pylori-positive participants (OR = 0.13, 95%CI: 0.04–0.42, p trend = 0.00). Conclusions:Both Trans-Lycopene and β-Cryptoxanthin intake showed a strong protective effect against stomach cancer. The findings suggest that these two types of fat-soluble micronutrients would be considered as an anti-cancer therapy for both primary and secondary prevention.Key Words: Stomach cancer, Helicobacter pylori, Trans-Lycopene and β-Cryptoxanthin intake     

A Case-Control Study of Gallstones: A Major Risk Factor for Biliary Tract Cancer

Because of the strong association between gallstones and biliary tract cancer, we conducted a case-control study of gallstones at Niigata Cancer Center Hospital. Eighty-six cases with gallstones (33 males and 53 females) and 116 hospital controls (56 males and 60 females) were surveyed by means of a self-administered questionnaire. Gallstones were categorized into cholesterol stones (25 cases) and pigment stones (30 cases) based on the appearance of the stones. In multivariate analyses based on an unconditional logistic regression model, the risk of total gallstones was positively associated with a taste for salty food (relative risk (RR)=2.31, 95% confidence interval (CI): 1.10–4.84), an intake of lettuce and cabbage (RR = 2.98, 95% CI: 1.47–6.06) and a family history of biliary diseases (RR=5.63, 95% CI: 1.76–17.95), and inversely associated with an intake of salted and dried fish (RR=0.16, 95% CI: 0.04–0.64). When analyzed by type of stones, cholesterol stones were associated with a taste for oily food (RR = 3.87, 95% CI: 1.36–11.03) and pigment stones were positively associated with professional or administrative occupation (RR = 4.74, 95% CI: 1.35–16.68) and inversely associated with a taste for less greasy food (RR = 0.28, 95% CI: 0.10–0.83). Some of these results are consistent with the results of our previous study on biliary tract cancer.