Displaying publications 1 - 20 of 75 in total

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  1. Fåhraeus R, Fu HL, Ernberg I, Finke J, Rowe M, Klein G, et al.
    Int J Cancer, 1988 Sep 15;42(3):329-38.
    PMID: 2843473
    Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.
  2. Foong YT, Cheng HM, Sam CK, Dillner J, Hinderer W, Prasad U
    Int J Cancer, 1990 Jun 15;45(6):1061-4.
    PMID: 1693600
    The Epstein-Barr virus nuclear antigen I (EBNA I) is the only latent EBV antigen consistently expressed in malignant tissues of the nasopharynx. A 20-amino-acid synthetic peptide, p107 contains a major epitope of EBNA I. We tested sera from 210 patients with nasopharyngeal carcinoma (NPC) and from 128 normal individuals (NHS) for IgA antibodies to p107 using an enzyme-linked immunosorbent assay (ELISA). Whereas 191/210 (91%) of NPC patients had IgA antibodies to p107, only 17/128 (13.3%) of NHS had such antibodies and only 6/57 (10.5%) of sera from patients with malignancies other than NPC had IgA-p107 reactivity. Thirty-nine salivary samples from 46 NPC patients (84.8%) also contained IgA-p107 antibodies whereas only 3/42 (7.1%) of normal saliva samples were IgA-p107 positive. The results suggest that IgA antibodies to EBNA I may become a useful, easily measurable, marker for NPC.
  3. Goh SH, Hew NF, Norhanom AW, Yadav M
    Int J Cancer, 1994 May 15;57(4):529-31.
    PMID: 8181855
    Inhibition of tumour promotion by various vitamin E compounds (tocopherols and tocotrienols) and some of their dimers was examined by an in vitro assay utilizing the activation of Epstein-Barr virus (EBV) early antigen (EA) expression in EBV-genome-carrying human lymphoblastoid cells. The results reveal that gamma- and delta-tocotrienols derived from palm oil exhibit a strong activity against tumour promotion by inhibiting EBV EA expression in Raji cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). However, alpha- and gamma-tocopherols and dimers of gamma-tocotrienol or gamma-tocopherol lack this activity.
  4. Peh SC, Sandvej K, Pallesen G
    Int J Cancer, 1995 May 4;61(3):327-32.
    PMID: 7729943
    Epstein-Barr virus (EBV) type B, a less potent transformer of B lymphocytes than type A, has rarely been detected in EBV-associated neoplasms except in AIDS-related lymphomas, in which about 50% of the cases contained this sub-type. In this study we analyzed the association of EBV and the distribution of virus sub-types in Asian non-Hodgkin's lymphoma (NHL) of the upper aerodigestive tract. We studied archival material of 29 NHL cases from Malaysia. B- and T-cell associated antigens were demonstrated by immunohistochemistry, and EBV early RNA EBER-1 was demonstrated using the RNA in situ hybridization technique. EBV was detected in the majority of tumour cells in 11/13 T-NHL but in only 1/16 B-NHL. EBV was sub-typed by single-step polymerase chain reaction of the EBNA-2 gene. This was successful in 9/10 cases of EBER-1-positive tumours and all contained type-A virus only. Our results showed a preponderance of T-cell lymphoma of the upper aerodigestive tract in the ethnic Chinese group of Malaysian patients, and EBV was strongly associated with T-NHL but not with B-NHL. Our results suggest that type-A EBV is the prevalent sub-type in Asian NHL of the upper aerodigestive tract, similarly to findings in Asian nasopharyngeal carcinoma.
  5. Armstrong RW, Imrey PB, Lye MS, Armstrong MJ, Yu MC, Sani S
    Int J Cancer, 1998 Jul 17;77(2):228-35.
    PMID: 9650558 DOI: 10.1002/(SICI)1097-0215(19980717)77:2<228::AID-IJC
    We interviewed 282 histologically confirmed cases of nasopharyngeal carcinoma (NPC) in Chinese residents of Selangor and the Federal Territory, Malaysia, and an equal number of Chinese age-, sex-, and length-of-residence-matched controls sampled from the general population. Consumption of 55 dietary items during childhood, and 5 years pre-diagnosis of NPC, was analyzed by univariate and multivariate methods. Four salted preserved foods (fish, leafy vegetables, egg and root), fresh pork/beef organ meats and beer and liquor consumption exhibited strong positive associations, and 4 vegetable/fruit combinations strong negative associations with NPC. Factor analysis and multivariable modeling using estimated factor scores strongly supported separate effects on NPC of vegetables/fruits, salted preserved foods, pork/beef organ meats and beer/liquor consumption. Multivariable modeling associated NPC most clearly with high consumption of salted fish, salted eggs, pork/beef liver and beer and low consumption of Chinese flowering cabbage, oranges/tangerines and shrimp. A strong residual association of social class with NPC remained after adjustment for diet, which is consistent with a substantial role for non-dietary environmental factors.
  6. Ng JH, Nesaretnam K, Reimann K, Lai LC
    Int J Cancer, 2000 Oct 1;88(1):135-8.
    PMID: 10962451
    Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.
  7. Chan BC, To KF, Pang JC, Chung YF, Lo KW, Tong JH, et al.
    Int J Cancer, 2002 Dec 10;102(5):492-8.
    PMID: 12432552
    A panel of monoclonal antibodies specific to Hong Kong Chinese nasopharyngeal carcinoma (NPC)-associated Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) variants has been generated. These monoclonal antibodies not only differentiate the Hong Kong Chinese NPC-associated LMP1 variants from the prototype B95-8 LMP1, derived from Caucasian infectious mononucleosis, but also differentiate the 2 highly homologous LMP1 deletion variants commonly found in Hong Kong primary NPC. The predominant deletion type variant, DV-Asp335, is characterized by an aspartic acid at residue 335 located in the cytoplasmic C-terminal region, whereas the other minor deletion variant, DV-Gly335, has a glycine in the same residue position. 335D is hitherto found predominantly in LMP1 of the China 1 strain in association with NPC in the Chinese populations located in southern China and Malaysia. These antibodies, which are applicable in ELISA, immunofluorescence, immunoprecipitation, immunoblotting and immunohistochemistry on paraffin sections, are the first variant-specific anti-LMP1 monoclonal antibodies produced, and will be useful in investigating the functional significance of 335D in NPC.
  8. Kim LH, Peh SC, Poppema S
    Int J Cancer, 2003 Nov 1;107(2):250-5.
    PMID: 12949802
    Isolation of single cells permits analysis of DNA or RNA from individual cells among heterogeneous populations. This technique is particularly useful in the study of classical Hodgkin's lymphoma (cHL) due to the scarcity of H/RS tumor cells among large numbers of reactive leukocytes. In a previous study, we found a high frequency of dual LMP-1 variant (concurrent presence of deleted and nondeleted variants) in cHL from whole-tissue sections. For the present study, we applied a single-cell isolation technique to determine the LMP-1 oncogene variant in EBV-associated H/RS cells. Five cases of EBV-infected cHL, containing nondeleted (n=1), deleted (n=1) and dual infection (n=3) based on whole-tissue section analysis, were selected for study. Paraffin-embedded tissue sections were stained with antibody to LMP-1 and positively stained H/RS cells isolated using a semiautomated micromanipulator. Each isolated single cell was subjected to PCR for amplification of the LMP-1 gene flanking the 30 bp deletion region and Xho1 restriction site. Cases with either nondeleted variant or the deleted variant showed similar LMP-1 variant expression in isolated single H/RS cells. However, 1 of the 3 cases with dual variants showed only the deleted variant in H/RS cells. The other 2 cases showed mixed patterns of deleted, nondeleted and dual LMP-1 variants in isolated single H/RS cells. All cases showed loss of the Xho1 restriction site, with the exception of the case with nondeleted LMP-1. Results of single-H/RS cell analysis of the Xho1 restriction site concur with those of whole-tissue section amplification. A mixed pattern of LMP-1 variants was observed in isolated H/RS cells, and it is speculated that this is due to the accumulation of mutation and deletion events.
  9. Lee CH, Ko AM, Warnakulasuriya S, Yin BL, Sunarjo, Zain RB, et al.
    Int J Cancer, 2011 Oct 1;129(7):1741-51.
    PMID: 21128235 DOI: 10.1002/ijc.25809
    Health risks stemming from betel-quid (BQ) chewing are frequently overlooked by people. Updated epidemiological data on the increased BQ use among Asian populations using comparable data collection methods have not been widely available. To investigate the prevalence, patterns of practice and associated types of oral preneoplastic disorders, an intercountry Asian Betel-quid Consortium study (the ABC study) was conducted for Taiwan, Mainland China, Malaysia, Indonesia, Nepal and Sri Lanka. A random sample of 8,922 subjects was recruited, and the data were analyzed using survey-data modules adjusted for the complex survey design. Chewing rates among men (10.7-43.6%) were significantly higher than women (1.8-34.9%) in Taiwan, Mainland China, Nepal and Sri Lanka, while women's rates (29.5-46.8%) were higher than that for men (9.8-12.0%) in Malaysia and Indonesia. An emerging, higher proportion of new-users were identified for Hunan in Mainland China (11.1-24.7%), where Hunan chewers have the unique practice of using the dried husk of areca fruit rather than the solid nut universally used by others. Men in the Eastern and South Asian study communities were deemed likely to combine chewing with smoking and drinking (5.6-13.6%). Indonesian women who chewed BQ exhibited the highest prevalence of oral lichen planus, oral submucous fibrosis and oral leukoplakia (9.1-17.3%). Lower schooling, alcohol drinking and tobacco smoking were identified as being associated with BQ chewing. In conclusion, the ABC study reveals the significant cultural and demographic differences contributing to practice patterns of BQ usage and the great health risks that such practices pose in the Asian region.
  10. Devi CR, Tang TS, Corbex M
    Int J Cancer, 2012 Dec 15;131(12):2869-77.
    PMID: 22407763 DOI: 10.1002/ijc.27527
    We determined the incidences of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) subtypes among breast cancer cases in Sarawak, Malaysia and their correlation with various risk factors in the three ethnic groups: Chinese, Malay and native. Subtype status was ascertained for 1,034 cases of female breast cancer (93% of all cases diagnosed since 2003), and the age-standardized incidence rates (ASRs) of each subtype were inferred. Case-case comparisons across subtypes were performed for reproductive risk factors. We found 48% luminal A (ER+/PR+/HER2-), 29% triple-negative (ER-/PR-/HER2-), 12% triple-positive (ER+/PR+/HER2+) and 11% HER2-overexpressing (ER-/PR-/HER2+) subtypes, with ASRs of 10.6, 6.0, 2.8 and 2.8 per 100,000, respectively. The proportions of subtypes and ASRs differed significantly by ethnic groups: HER2-positive cases were more frequent in Malays (29%; 95% CI [23;35]) than Chinese (22%; [19;26] and natives (21%; [16;26]); triple-negative cases were less frequent among Chinese (23%; [20;27]) than Malays (33%; [27;39]) and natives (37%; [31;43]). The results of the case-case comparison were in accordance with those observed in western case series. Some uncommon associations, such as between triple-negative subtype and older age at menopause (OR, 1.59; p < 0.05), were found. The triple-negative and HER2+ subtypes predominate in our region, with significant differences among ethnic groups. Our results support the idea that the risk factors for different subtypes vary markedly. Westernized populations are more likely to have factors that increase the risk for the luminal A type, while risk factors for the triple-negative type are more frequent in local populations.
  11. Chin YM, Mushiroda T, Takahashi A, Kubo M, Krishnan G, Yap LF, et al.
    Int J Cancer, 2015 Feb 1;136(3):678-87.
    PMID: 24947555 DOI: 10.1002/ijc.29035
    Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10(-9)). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p(HLA-A-aa-site-99) = 3.79 × 10(-8), p(rs1136697) = 3.79 × 10(-8)) and T-cell receptor binding site (p(HLA-A-aa-site-145) = 1.41 × 10(-4), p(rs1059520) = 1.41 × 10(-4)) of the HLA-A. We also detected strong association signals in the 5'-UTR region with predicted active promoter states (p(rs41545520) = 7.91 × 10(-8)). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.
  12. Dionne KR, Warnakulasuriya S, Zain RB, Cheong SC
    Int J Cancer, 2015 Feb 1;136(3):503-15.
    PMID: 24482244 DOI: 10.1002/ijc.28754
    Despite commendable progress in the prevention, detection, and treatment of a wide variety of solid tumor types, oral squamous cell carcinoma (OSCC) remains a significant health burden across the globe. OSCC carcinogenesis involves accumulation of genetic alterations that coincide with the multistep malignant transformation of normal oral epithelium. OSCC is often first diagnosed at late stages of the disease (advanced regional disease and/or metastasis). Delayed diagnosis precludes successful treatment and favorable outcomes. In clinical practice, opportunities exist to identify patients with oral potentially malignant disorders (OPMDs), which precede the development of cancer. This review addresses the current status of laboratory and clinical research on OPMDs, with emphasis on leukoplakia and erythroplakia. OSF is also presented, though there is a paucity of published studies on this disorder. We focus on findings that could translate into earlier diagnosis and more efficacious treatment of those lesions with significant malignant potential. We explore how markers of OPMD malignant transformation might be implemented into current diagnostic practice to help clinicians objectively stratify patients into treatment/follow-up groups according to relative risk. We provide an overview of recently concluded and ongoing OPMD chemoprevention trials. We describe laboratory OPMD models that can be used to not only to reveal the genetic and molecular intricacies of oral cancer but also to develop novel screening methods and therapeutic approaches. Finally, we call for targeted screening programs of at-risk populations in order to facilitate diagnosis and treatment of OPMD and early OSCC.
  13. Steffen A, Huerta JM, Weiderpass E, Bueno-de-Mesquita HB, May AM, Siersema PD, et al.
    Int J Cancer, 2015 Aug 01;137(3):646-57.
    PMID: 25598323 DOI: 10.1002/ijc.29432
    General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.
  14. Ricceri F, Fasanelli F, Giraudo MT, Sieri S, Tumino R, Mattiello A, et al.
    Int J Cancer, 2015 Aug 15;137(4):940-8.
    PMID: 25650288 DOI: 10.1002/ijc.29462
    Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.
  15. Fortner RT, Ose J, Merritt MA, Schock H, Tjønneland A, Hansen L, et al.
    Int J Cancer, 2015 Sep 01;137(5):1196-208.
    PMID: 25656413 DOI: 10.1002/ijc.29471
    Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet  = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet  = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.
  16. Wozniak MB, Brennan P, Brenner DR, Overvad K, Olsen A, Tjønneland A, et al.
    Int J Cancer, 2015 Oct 15;137(8):1953-66.
    PMID: 25866035 DOI: 10.1002/ijc.29559
    Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (ptrend  = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.
  17. Campa D, Rizzato C, Stolzenberg-Solomon R, Pacetti P, Vodicka P, Cleary SP, et al.
    Int J Cancer, 2015 Nov 01;137(9):2175-83.
    PMID: 25940397 DOI: 10.1002/ijc.29590
    A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.
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