bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic susceptibility and gastric cancer risk
Authors: González Carlos A. , Sala Núria , Capellá Gabriel 
Published: September 2002

AbstractThe aim of the present paper is to review and evaluate, in a comprehensive manner, the most recent published evidence on the contribution of genetic susceptibility to gastric cancer risk in humans. We have identified all studies available in MEDLINE published up to October 2001. Only studies carried out in humans and comparing gastric cancer cases with at least 1 standard control group were included in the analysis. We were able to find 31 articles based on 25 case‐control studies carried out in Caucasian, Asian and African populations. Most of the studies assess the effect of genes involved in detoxifying pathways (n = 12) and inflammatory responses (n = 7). The most widely studied is the GSTM1 null polymorphism. Only a very few studies have evaluated the risk of gastric cancer associated with genes acting on mucosa protection, oxidative damage and DNA repair. The most consistent results are the increased gastric cancer risk associated with IL1B and NAT1 variants, which may account for up to 48% of attributable risk of gastric cancer. Only polymorphisms at HLA‐DQ, TNF and CYP2E genes may confer some protective effect against gastric cancer. The most important limitations that preclude definitive conclusions are (i) the lack of appropriate control of potential sources of bias (only 5 population‐based studies have been published so far); (ii) the low number of cases analyzed (14 studies included fewer than 99 cases); and (iii) the low number of studies (n = 3) offering concomitant analysis of genetic susceptibility and exposure to relevant cofactors (Helicobacter pylori infection, diet and smoking). We conclude that the scientific data on the role of genetic factors in gastric cancer risk are promising. The lack of association reported so far should be considered with caution due to significant limitations in study design. Cohort studies taking into account simultaneously the different genetic and environmental factors potentially involved in gastric tumorigenesis are needed to ascertain not only the relative contribution of these factors to tumor development but also the contribution of their putative interactions. © 2002 Wiley‐Liss, Inc.
Impairment of stimulation by estrogen of insulin‐activated nitric oxide synthase in human breast cancer
Authors: Guha Manti , Biswas Jaydip , Tirkey Jaya , Sinha A. Kumar 
Published: September 2002

AbstractNitric oxide (NO) is reported to have several important effects in the control of neoplasm. We have reported before the presence of an insulin‐activated constitutive form of membrane‐bound nitric oxide synthase (IANOS) in various cells. Since the insulin‐induced NO synthesis by IANOS could have important consequences on the pathophysiology of neoplastic cells, the role of estrogen on the activity of IANOS in malignant and nonmalignant breast tissue as well as in erythrocytes in breast cancer patients was determined. It was found that the IANOS activity of nonmalignant breast tissue was maximally stimulated by 4‐fold over the basal activity in the presence of physiologic amounts of estrogen (8–32 nM). The enzymic activity was, however, inhibited by estrogen both below and above this range when compared to appropriate controls. In contrast, both the basal IANOS activity and the stimulatory effect of estrogen was markedly impaired in malignant breast tissue and in erythrocytes in these patients. It was also noted that tamoxifen, a widely used nonsteroidal compound in breast cancer, mimicked estrogen both in the stimulation and in the inhibition of IANOS activity in both of the tissues. These results indicated the probable existence of a novel pathway for estrogen effect independent of nuclear receptor for the stimulation of IANOS activity that might have important consequences in breast cancer and suggested that some of the beneficial effects of tamoxifen could be related to its estrogen‐mimicking effect on IANOS independent of hormone‐responsive elements sequence in the DNA. © 2002 Wiley‐Liss, Inc.
p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori‐associated chronic gastritis
Authors: Hiyama Toru , Tanaka Shinji , Kitadai Yasuhiko , Ito Masanori , Sumii Masaharu , Yoshihara Masaharu , Shimamoto Fumio , Haruma Ken , Chayama Kazuaki 
Published: September 2002

Abstractp53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori‐associated chronic gastritis (H. pylori‐CG). We, therefore, examined the polymorphism in 117 gastric cancer patients (72 intestinal type and 45 diffuse type) with H. pylori‐CG and 116 H. pylori‐CG patients without gastric cancer as controls. Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) analysis was performed to analyze the p53 codon 72 polymorphism. The crude genotypic frequencies in the gastric cancer patients were similar to those of the controls. However, when gastric cancers were classified by histologic subtype, the Pro/Pro was more frequent in the patients with diffuse type gastric cancer than in the controls (22.2% of cases vs. 12.1% of controls). The Pro/Pro genotype was associated with a 2.98‐fold higher risk of diffuse‐type cancer compared to the Arg/Arg genotype (95% confidence interval [CI] 1.07–8.32, p = 0.038). These results suggest that the Pro/Pro genotype at p53 codon 72 contributes to susceptibility for diffuse‐type gastric cancer in patients with H. pylori‐CG. The p53 codon 72 polymorphism may serve as the genetic marker for the risk assessment of the diffuse‐type gastric cancer development in patients with H. pylori‐CG. © 2002 Wiley‐Liss, Inc.
Family history of breast cancer, age and benign breast disease
Authors: Webb Penelope M. , Byrne Celia , Schnitt Stuart J. , Connolly James L. , Jacobs Timothy , Peiro Gloria , Willett Walter , Colditz Graham A. 
Published: September 2002

AbstractA major risk factor for breast cancer is having a first‐degree family history of the disease. Benign breast disease (BBD), particularly atypical hyperplasia, is also associated with an increased risk of breast cancer. However, the relationship between family history of breast cancer and BBD is unclear. From 1989 through 1997, 80,995 participants in the Nurses' Health Study II were followed; 16,849 reported a first diagnosis of BBD. Pathology slides were reviewed for 1,465 women who reported having a tissue biopsy, and these were classified as nonproliferative BBD, proliferative BBD without atypia or atypical hyperplasia. Women with a family history of breast cancer were more likely to report a physician diagnosis of BBD [rate ratio (RR) = 1.38, 95% confidence interval (CI) 1.29–1.46]. The magnitude of this association declined with age from RR = 1.96 (95% CI 1.55–2.47) at 25–29 years to RR = 1.20 (95% CI 0.95–1.52) at age 45–50 years. Among women with proliferative disease, those with a family history of breast cancer were almost 3 times as likely to have atypia (prevalence odds ratio = 2.72, 95% CI 1.23–5.89) than those with no family history. In conclusion, women with a family history of breast cancer appear to be at increased risk of being diagnosed with BBD, in particular the high‐risk types of BBD associated with a greatly increased risk of breast cancer. This link adds weight to the belief that BBD with atypia is a precursor or marker lesion for breast cancer. © 2002 Wiley‐Liss, Inc.
Increased incidence rate of colorectal tumors due to the intake of a soluble dietary fiber in rat chemical carcinogenesis can be suppressed by substituting partially an insoluble dietary fiber for the soluble one
Authors: Okazaki Hideki , Nishimune Takahiro , Matsuzaki Hiroshi , Miura Tsutomu , Morita Shigeru , Yanagimoto Yukio , Yamagishi Hiroyuki , Yamada Kazuhiko , Ikegami Sachie 
Published: September 2002

AbstractIn epidemiologic studies on human colorectal tumors, results on the relative protective effect of soluble and insoluble fibers are not consistent. We studied in this work the effect in rats of feeding guar gum or guar gum together with cellulose on the incidence of colorectal tumors induced by 1,2‐dimethylhydrazine. The results were as follows: (i) The enhancement of tumor formation by feeding solely guar gum (guar gum group) was suppressed completely when two‐thirds of the guar gum was replaced with cellulose (cellulose‐guar gum group). The odds ratio for tumor formation was 0.075 (95% CI 0.006–0.936, p = 0.044) for guar gum group vs. no fiber control and 0.833 (0.134–5.167, p = 0.83) for cellulose‐guar gum group vs. the control. (ii) In both groups, serum cholesterol and triglyceride levels decreased significantly compared to the no fiber control group, and fecal excretion of total bile acids almost doubled. (iii) In guar gum group rats, the deconjugation activity (β‐glucuronidase, β‐glucosidase) was higher than the control or cellulose‐guar gum group rats. (iv) The amount of cecal short‐chain fatty acids was almost double in guar gum group rats compared to the cellulose‐guar gum group or the control rats, and pH of the cecal content of the guar gum group rats had a tendency to be lower. (v) The concentration of fecal secondary bile acids was extremely low in the younger rats of the guar gum group. From these results, it seemed significant to study the cancer preventive effect of the mixed feeding to experimental animals of water‐soluble and insoluble fibers instead of the singular feeding. © 2002 Wiley‐Liss, Inc.
Broadened ligand responsiveness of androgen receptor mutants obtained by random amino acid substitution of H874 and mutation hot spot T877 in prostate cancer
Authors: Steketee Karine , Timmerman Leon , Ziel‐van der Made Angelique C.J. , Doesburg Paul , Brinkmann Albert O. , Trapman Jan 
Published: September 2002

AbstractIn a subset of endocrine therapy‐resistant prostate cancers, amino acid substitutions H874Y, T877A and T877S, which broaden ligand specificity of the ligand binding domain (LBD) of the androgen receptor (AR), have been detected. To increase our knowledge of the role of amino acid substitutions at these specific positions in prostate cancer, codons 874 and 877 were subjected to random mutagenesis. AR mutants were screened in a yeast readout system for responsiveness to 5α‐dihydrotestosterone, progesterone and dehydroepiandrosterone. At position 874, only the histidine to tyrosine substitution could broaden AR ligand specificity. At position 877, 4 ligand specificity broadening substitutions were found: T877A, T877S, T877C and T877G. The latter 2 were not found in prostate cancer. The AR mutants were tested in mammalian (Hep3B) cells for responsiveness to 13 different ligands. All mutants displayed their own ligand specificity spectrum. Importantly, AR(H874Y) and AR(T877A) could be activated by cortisol. According to the 3‐dimensional structure of the AR LBD, T877 interacts directly with the 17β‐hydroxyl group of androgens. All amino acid substitutions identified at position 877 had smaller side chains than the threonine in the wild‐type receptor, indicating that increased space in the ligand binding pocket is important in broadened ligand specificity. Because H874 does not interact directly with the ligand, its substitution by a tyrosine is expected to change the ligand binding pocket conformation indirectly. For T877C and T877G substitutions, 2‐point mutations are required, and for H874Y, T877A and T877S substitutions, only a 1‐point mutation is sufficient. This most likely explains that the latter 3 have been found in prostate cancer. © 2002 Wiley‐Liss, Inc.
HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer
Authors: van Gils Carla H. , Conway Kathleen , Li Yu , Taylor Jack A. 
Published: September 2002

AbstractThe HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb downstream from the HRAS1 gene, has been reported to be associated with risk of various cancers. To examine whether individuals with rare HRAS1 VNTR alleles are at increased risk of bladder cancer we carried out a case control study with 230 bladder cancer cases and 203 hospital‐based controls frequency‐matched on ethnicity, gender and age. For genotyping we used a PCR‐based long‐gel electrophoretic assay that provides precise allele size discrimination. We did not find evidence of a strong overall effect of the HRAS1 VNTR on bladder cancer risk. Genotype data for whites and blacks were analyzed separately, but the number of black subjects was too small to estimate meaningful odds ratios. Compared to white subjects with 2 common alleles, the odds ratio (OR) for white subjects with 1 rare allele was 0.9 (95% confidence interval (CI) = 0.5–1.4) and for those with 2 rare alleles OR = 1.7 (95% CI = 0.6–5.4). HRAS1 genotype may be related to the prognosis of bladder cancer, however, because incident cases, i.e., newly diagnosed cases had a higher frequency of rare alleles than did prevalent cases, i.e., cases already existing at the time of recruitment. Repeating the analyses with incident cases only (n = 53), the OR for subjects with 1 rare allele was 1.2 (95% CI = 0.6–2.4) and for those with 2 rare alleles 3.2 (95% CI = 0.8–13.7). The number of incident cases was too small to draw firm conclusions on a possible association with a subgroup of tumors with a poor prognosis. Published 2002 Wiley‐Liss, Inc.
Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor‐α gene in endometrial carcinoma cells
Authors: Mizumoto Hisanobu , Saito Tsuyoshi , Ashihara Koji , Nishimura Makoto , Tanaka Ryoichi , Kudo Ryuichi 
Published: September 2002

AbstractIt is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor invasion, is not well known in endometrial carcinoma. In our study, we focused on the influence of estrogen and its receptor in invasion and matrix metalloproteinases (MMPs), which are known to be important in tumor invasion, as well as on endometrial carcinoma cells. The growth of Ishikawa cells, to which an estrogen receptor‐α expressing vector was transfected, was accelerated by 17β‐estradiol as was the acceleration of the expression of cyclin D1. By invasion assay, in conditions with 17β‐estradiol, the invasiveness of Ishikawa cells was enhanced. Furthermore, according to the accelerated invasiveness, the expression of MMP‐1, ‐7 and ‐9 and Ets‐1 was enhanced. These results suggest that activation of ER‐α by estrogen results in tumor progression by stimulating cell growth and invasiveness via acceleration of the expression of MMPs. © 2002 Wiley‐Liss, Inc.
Critical tumor‐suppressor gene regions on chromosome 3P in major human epithelial malignancies: Allelotyping and quantitative real‐time PCR
Authors: Braga Eleonora , Senchenko Vera , Bazov Igor , Loginov Witaly , Liu Jian , Ermilova Valeria , Kazubskaya Tatiana , Garkavtseva Raisa , Mazurenko Natalia , Kisseljov Fedor , Lerman Michael I. , Klein George , Kisselev Lev , Zabarovsky Eugene R. 
Published: September 2002

AbstractTo ascertain the involvement of human chromosome 3p and its established critical TSG regions in various epithelial malignancies, 21 polymorphic and 2 nonpolymorphic 3p markers were allelotyped in nonpapillary RCC, NSCLC, CC and BC from a total of 184 patients. LOH was observed with high frequency in all types of cancer studied: RCC (52/57, 91%), BC (41/51, 80%), NSCLC (30/40, 75%) and CC (27/36, 75%). Interstitial deletions, believed to signal TSG inactivation, were verified using the “L‐allele rule” and real‐time quantitative PCR. Significant correlation was observed between DNA copy numbers for 2 nonpolymorphic STS markers and LOH data for adjacent polymorphic loci. Interstitial deletions in 3p were demonstrated for all cancer types studied. However, the distribution of different types of deletion was characteristic for tumors from various locations. Large terminal deletions were predominantly seen in RCC and NSCLC (51% and 40%, respectively), correlating with clear cell RCC and squamous cell carcinomas of the lung. In addition to the LUCA region at 3p21.3 (centromeric), we found that the AP20 region (3p21.3, telomeric) was frequently affected in all 4 cancers, suggesting that this newly defined critical region contains multiple TSGs. Moreover, at least 3 candidate cancer‐specific loci were identified. The telomeric 3p26.1‐p25.3 region was predominantly deleted in RCC and NSCLC. The D3S1286 and D3S3047 markers (3p25.2‐p24.3) were deleted nonrandomly in NSCLC. High‐frequency LOH was detected in a segment mapped closely distal to the LUCA site (3p21.3), around the D3S2409 and D3S2456 markers. © 2002 Wiley‐Liss, Inc.
Characterization of androgen receptor and nuclear receptor co‐regulator expression in human breast cancer cell lines exhibiting differential regulation of kallikreins 2 and 3
Authors: Magklara Angeliki , Brown Theodore J. , Diamandis Eleftherios P. 
Published: September 2002

AbstractAccumulating evidence indicates that androgens and the androgen receptor modulate the development and progression of breast adenocarcinoma; however, the precise role and actions remain poorly defined. We examined previously the steroid hormone regulation of 2 known androgen‐regulated kallikreins, KLK3 (encoding PSA) and KLK2 (encoding human kallikrein 2 or hK2) in BT‐474, T‐47D, ZR75‐1, MCF‐7, MFM‐223 and BT‐20 human breast cancer cells and found that they were differentially regulated, with the cells showing variable responses to androgen. To determine if this variable response was reflected by differences in androgen receptor, we characterized the expression of androgen receptor in these cells by Western blot analysis and saturation binding analysis. In addition, we sequenced androgen receptor cDNA from each of these cell lines to check whether any androgen receptor mutations were present. The expression of 11 nuclear receptor co‐regulatory factors (SRC‐1, AIB1, ARA24, ARA54, ARA55, ARA70, ARA160, FHL2, PDEF, NCoR1, SMRT) was compared in these cell lines by semi‐quantitative RT‐PCR to determine if the pattern of receptor co‐activators or ‐repressors expressed in these cells might explain the differential regulation of KLK2 and KLK3. The levels of androgen receptor varied among the cell lines, but did not correlate with hK2 and PSA secretion determined previously. No mutations within the coding regions of the receptor were detected. With the exception of receptor expressed by MCF‐7 cells, the polymorphic CAG repeat length was in the normal range. Every breast cancer cell line exhibited a distinct expression pattern of the nuclear receptor co‐regulators examined raising the possibility that the relative levels of these co‐activators/‐repressors might differentially modulate androgen receptor transcriptional activity within the promoter/enhancer region of KLK2 and KLK3 of these cells. © 2002 Wiley‐Liss, Inc.
Soluble HLA‐DR is a potent predictive indicator of disease progression in serum from early‐stage melanoma patients
Authors: Rebmann Vera , Ugurel Selma , Tilgen Wolfgang , Reinhold Uwe , Grosse‐Wilde Hans 
Published: September 2002

AbstractDespite numerous therapeutic options, the prognosis of malignant melanoma, once metastasized, is still poor. Thus, the search for reliable methods to identify patients with high risk of disease progression as early as possible is of major importance. In our study, we analyzed the predictive value of soluble HLA‐DR (sHLA‐DR) in comparison to S100‐β in serum from 183 melanoma patients of different stages of disease and with or without current therapy using immunosorbent assays. sHLA‐DR serum levels of 121 healthy individuals served as controls. We found significantly (p< 0.0005) reduced sHLA‐DR serum levels in melanoma patients (0.70 ± 0.08 SEM μg/ml) compared to controls (1.49 ± 0.10 SEM μg/ml). Reduced sHLA‐DR and increased S100‐β levels were associated with advanced disease stages and tumor load. S100‐β was increased under cytostatic therapy (p< 0.0005), whereas sHLA‐DR was not influenced by therapy modalities. Univariate analysis showed an association of sHLA‐DR < 0.3 μg/ml and S100‐β > 0.12 μg/l with poor overall (p= 0.021 andp= 0.0009) and progression‐free survival (p< 0.0005 andp= 0.0025). Multivariate analysis revealed disease stage (p= 0.0093) and tumor burden (p< 0.0005) as independent predictive factors for overall survival, and sHLA‐DR (p= 0.0007) and tumor burden (p= 0.0015) for progression‐free survival. In contrast to S100‐β, sHLA‐DR serum concentrations < 0.3 μg/ml were strongly associated (p= 0.0001) with poor progression‐free survival in a subgroup of 60 nonmetastasized patients. In conclusion, our results suggest sHLA‐DR as a potent prognostic serum marker in melanoma patients superior to S100‐β in helping to identify early‐stage patients at high risk of disease progression. © 2002 Wiley‐Liss, Inc.
Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population
Authors: Xing Deyin , Qi Jun , Miao Xiaoping , Lu Wenfu , Tan Wen , Lin Dongxin 
Published: September 2002

AbstractEsophageal squamous cell carcinoma (ESCC), which is prevalent in China, is believed to be induced by environmental carcinogens. Accumulating evidence has shown that individual variation in DNA repair capacity resulting from genetic polymorphism influences risk of environmental carcinogenesis. We therefore investigated the associations between genetic polymorphisms in the DNA repair genes XRCC1 (Arg194Trp and Arg399Gln) and XPD (Asp312Asn and Lys751Gln) and risk of ESCC in an at‐risk Chinese population. Genotypes were determined by a PCR‐based approach in 433 patients with ESCC and 524 frequency‐matched normal controls. We found that individuals with Trp/Trp genotype at XRCC1 Arg194Trp site had a 2‐fold increased risk of this disease compared to Arg/Arg genotype (adjusted OR = 1.98; 95% CI 1.26–3.12). Furthermore, when compared to Arg/Arg and Arg/Trp genotype combined, homozygote for Trp/Trp genotype significantly increased the risk of developing ESCC, with the adjusted OR being 2.07 (95% CI 1.34–3.20). However, the XRCC1 Arg399Gln polymorphism was not significantly associated with risk of ESCC, with the adjusted OR being 0.87 (95% CI 0.55–1.37). Neither Asp312Asn nor Lys751Gln polymorphisms in the XPD gene influenced risk of ESCC in our study. These findings suggest that DNA repair gene XRCC1 but not XPD might play a role in esophageal carcinogenesis and might represent a genetic determinant in the development of the cancer. © 2002 Wiley‐Liss, Inc.