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FACTEURS DE RISQUES EPIDEMIOLOGIE
1- Integrating Epidermal Growth Factor Receptor Assay with Clinical Parameters
Improves Risk Classification for Relapse and Survival in Head-and-Neck Squamous
Cell Carcinoma Original Research Article
International Journal of Radiation Oncology*Biology*Physics, In Press, Corrected Proof,
Available online 21 August 2010
Christine H. Chung, Qiang Zhang, Elizabeth M. Hammond, Andy M. Trotti III, Huijun
Wang, Sharon Spencer, Hua-Zhong Zhang, Jay Cooper, Richard Jordan, Marvin H. Rotman,
K. Kian Ang
Purpose
Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an
independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by
which it can refine risk classification for overall survival (OS) and LRR in patients with head-andneck squamous cell carcinoma (HNSCC).
Methods and Materials
EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of
patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial.
Subsequently, data of the two series were pooled (N = 533) for conducting a recursive partitioning
analysis that incorporated clinical parameters (e.g., performance status, primary site, T and N
categories) and four molecular markers (EGFR, p53, Ki-67, and microvessel density).
Results
This study confirmed that patients with higher than median levels of tumor EGFR expression had a
lower OS (relative risk [RR]: 1.90, p = 0.0010) and a higher LRR (RR: 1.91, p = 0.0163). Of the four
markers analyzed, only EGFR was found to contribute to refining classification of patients into three
risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters
could identify patients having up to a fivefold difference in the risk of LRR.
Conclusions
Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved
the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting
patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing
specific therapeutic strategy warrants further investigation.
2- Role of NQO1 polymorphisms as risk factors for squamous cell carcinoma of the head and
neck Original Research Article
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Oral Oncology, Volume 41, Issue 9, October 2005, Pages 927-933
Asher Begleiter, Alia Norman, Darren Leitao, Teresa Cabral, Donna Hewitt, Sushu Pan,
Jennifer R. Grandis, Jill M. Siegfried, Samy El-Sayed, Donna Sutherland, David A. Ross, Paul D.
Kerr
Summary
A case:control study was carried out to determine if inactivating polymorphisms of the NQO1 gene at
bases 609 and 465 are associated with altered risk of developing squamous cell carcinoma of the
head and neck (SCCHN). Genotyping was carried out by PCR RFLP analysis on whole blood samples.
The frequency of the inactive 609T and active 609C forms, and the inactive 465T and active 465C forms, of
NQO1 were compared in patient and control groups by a logistic regression analysis and odds ratios
(ORs) were calculated. Participants were stratified by tobacco and alcohol use, and genotype
distributions in these sub-groups were compared. There were no significant differences in genotype
distribution between SCCHN patients and the control population for the base 609 or 465
polymorphisms. There were also no significant differences in genotype distributions between patient
and control groups for tobacco and/or alcohol users and non-users. Genotype distributions were
similar for SCCHN patients at all disease sites with the exception of the nasopharynx where there was
a higher incidence of the 609C:609T and 609T:609T genotypes. These results suggest that individuals
having either 609T or 465T alleles generally do not have an altered risk of developing SCCHN.
3- Clinicopathologic risk factors for distant metastases from head and neck squamous cell
carcinomas Original Research Article
European Journal of Surgical Oncology (EJSO), Volume 35, Issue 12, December 2009, Pages
1348-1353
X. Li, B. Di, Y. Shang, Y. Zhou, J. Cheng, Z. He
Abstract
Aims
The aim of this study is to investigate the clinicopathologic risk factors associated with distant
metastases (DMs) from head and neck squamous cell carcinomas (HNSCCs).
Methods
Between February 1990 and February 2000, a retrospective analysis of 391 HNSCC patients was
performed. The frequency and the clinicopathologic risk factors for DM were evaluated by using
univariate χ2 tests and multiple stepwise logistic regression models. Statistical analysis of overall
survival was performed by using Kaplan–Meier method.
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Results
44 patients (11.3%) developed DM in clinic. In a univariate analysis, clinical N stage, primary tumor
site, level of tumor invasion, pathologic N stage and number of levels with pathologic lymph node
were found to be significantly associated with the risk of DM. In a multivariate analysis, the most
significant risk factors were number of levels with pathologic lymph node, level of tumor invasion,
and primary tumor site. Kaplan–Meier analysis showed that overall survival rates of 44 patients with
DMs in clinic were 56.8% at 1 year, 9.1% at 3 years, and 6.8% at 5 years, respectively.
Conclusions
The number of levels with pathologic lymph node, the site of primary tumor and the level of tumor
invasion are decisive risk factors in determining the development of DM in head and neck SCC
patients. Patients with multilevel nodal involvement in neck, with laryngeal and hypopharyngeal
carcinomas, and patients with primary tumor invasion into muscular, bone or cartilage have the
highest risk of developing DM.
4- Squamous cell carcinoma of the head and neck in young Irish adults Original Research
Article
British Journal of Oral and Maxillofacial Surgery, Volume 44, Issue 3, June 2006, Pages 203206
E.M. O’Regan, C. Timon, O. Sheils, Margaret Codd, J.J. O’Leary, M. Toner
Abstract
Abstract
Classically, squamous cell carcinoma (SCC) of the head and neck is a disease of older adults, but
recently there have been reports of an increasing incidence in young people. This study of patients in
the Republic of Ireland compares sex distribution, sites, risk factors, stage and grade of tumour, and
nodal status of 130 patients with SCC of the head and neck, 30 of whom were less than 40 years old.
There was a highly significant association between age, smoking status, and site of tumour.
For the first time to our knowledge in a study such as this, the preoperative haematological status of
the patients was assessed, and although 15% were anaemic there was no significant difference in the
occurrence of anaemia between the younger and the older patients. We think that it is possible that the
biology of SCC of the head and neck in young people differs from that in older people.
5- The influence of clinical and demographic risk factors on the establishment of head and
neck squamous cell carcinoma cell lines Original Research Article
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Oral Oncology, Volume 43, Issue 7, August 2007, Pages 701-712
Jason S. White, Joel L. Weissfeld, Camille C.R. Ragin, Karen M. Rossie, Christa Lese Martin,
Michele Shuster, Chandramohan S. Ishwad, John C. Law, Eugene N. Myers, Jonas T. Johnson,
Susanne M. Gollin
Summary
The purpose of this study was to generate stable cell cultures from head and neck squamous cell
carcinomas (HNSCC), and retrospectively analyze the factors associated with successful cell line
establishment. Fifty-two HNSCC cell lines were isolated from a series of 199 tumors collected
between 1992 and 1997 at the University of Pittsburgh Medical Center. Cell lines were characterized
at the molecular and cellular level to determine the features associated with cell line formation.
Successful cell line formation was dependent on multiple factors, including gene amplification
involving chromosomal band 11q13, local and/or regional involvement of lymph nodes, and alcohol
usage. The establishment of HNSCC cell lines enriches the resources available for cancer research.
Our findings indicate that generation of stable cell lines from HNSCC is biased towards tumors with a
poor prognosis. Our 52 stable lines comprise one of the largest series of HNSCC cell lines in the
literature, with complete demographic, histopathologic, clinical, and survival data.
6- CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor
outcome in head and neck squamous cell carcinoma patients Original Research Article
Oral Oncology, Volume 45, Issue 9, September 2009, Pages e73-e79
Eloisa Helena Ribeiro Olivieri, Sabrina Daniela da Silva, Fernando Fernandes Mendonça, Yuri
Nagamine Urata, Daniel Onofre Vidal, Marcilia de Araujo Medrado Faria, Inês Nobuko
Nishimoto, Claudia Aparecida Rainho, Luiz Paulo Kowalski, Silvia Regina Rogatto
Summary
Head and neck squamous cell carcinoma (HNSCC) is associated with environmental factors, especially
tobacco and alcohol consumption. Most of the carcinogens present in tobacco smoke are converted
into DNA-reactive metabolites by cytochrome P450 (CYPs) enzymes and detoxification of these
substances is performed by glutathione S-transferases (GSTs). It has been suggested that genetic
alterations, such as polymorphisms, play an important role in tumorigenesis and HNSCC progression.
The aim of this study was to investigate CYP1A1, CYP1A2, CYP2E1, GSTM1, and GSTT1 polymorphisms
as risk factors in HNSCC and their association with clinicopathologic data. The patients comprised 153
individuals with HNSCC (cases) and 145 with no current or previous diagnosis of cancer (controls).
Genotyping of the single nucleotide polymorphisms (SNPs) of the CYP1A1, CYP1A2, and CYP2E1
genes was performed by PCR-RFLP and the GSTM1 and GSTT1 copy number polymorphisms (CNPs)
were analyzed by PCR-multiplex. As expected, a significant difference was detected for tobacco and
alcohol consumption between cases and controls (P < 0.001). It was observed that the CYP1A2*1D
(OR = 16.24) variant and GSTM1 null alleles (OR = 0.02) confer increased risk of HNSCC development
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FACTEURS DE RISQUES EPIDEMIOLOGIE
(P < 0.001). In addition, head and neck cancer alcohol consumers were more frequently associated
with the CYP2E1*5B variant allele than control alcohol users (P < 0.0001, OR = 190.6). The
CYP1A2*1C polymorphism was associated with tumor recurrence (log-rank test, P = 0.0161). The
CYP2E1*5B and GSTM1 null alleles were significantly associated with advanced clinical stages
(T3 + T4; P = 0.022 and P = 0.028, respectively). Overall, the findings suggested that the genetic
polymorphisms studied are predictors of risk and are also associated with tumor recurrence, since
they are important for determining the parameters associated with tumor progression and poor
outcomes in HNSCC.
7- Analysis of 724 cases of primary head and neck squamous cell carcinoma (HNSCC) with a
focus on young patients and p53 immunolocalization Original Research Article
Oral Oncology, Volume 45, Issue 9, September 2009, Pages 777-782
A.M.B. De Paula, L.R. Souza, L.C. Farias, G.T.B. Corrêa, C.A.C. Fraga, N.B. Eleutério, A.C.O.
Silveira, F.B.G. Santos, D.S. Haikal, A.L.S. Guimarães, R.S. Gomez
Summary
This study evaluated 724 primary head and neck squamous cell carcinoma (HNSCC) in young and old
patients, with regard to clinical profile and immunohistochemical expression of p53 protein.
Associations among age, epidemiological and clinicopathological parameters, and survival analysis
were evaluated. HNSCC in young people occurred in 14.5% (median age 40.7 years; male-to-female
ratio 5.9:1). A statistical association was demonstrated between age and family history of cancer, and
between age and anatomical site. Among older patients, a higher presence of disease was noted in
posterior sites. Expression of p53 was found in 71.7% of the samples and a higher expression was
noted in lesions of young patients. Survival analysis showed that the age parameter is not a reliable
prognostic factor for HNSCC. Among young patients, cervical metastasis was associated with worse
survival. The presence of a family history of cancer in young patients could indicate genetic
susceptibility and molecular disturbances in the p53 pathway in HNSCC of young and older patients
seem to be distinct.
8- Promoter polymorphisms of DNMT3B and the risk of head and neck squamous cell
carcinoma in Taiwan: A case–control study Original Research Article
Oral Oncology, Volume 43, Issue 4, April 2007, Pages 345-351
Kai-Ping Chang, Sheng-Po Hao, Chun-Ting Liu, Ming-Huei Cheng, Yu-Liang Chang, Yun-Shien
Lee, Tzu-Hao Wang, Chi-Neu Tsai
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Abstract
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Summary
Three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T
(−149C > T), −283T > C, and −579G > T might be a cancer susceptible factor for several cancers. In this
study, we genotyped 226 head-and-neck squamous-cell carcinoma (HNSCC) patients and 249
controls to examine the association between three SNPs of the DNMT3B promoter and the
associated risk of the development and/or metastasizing tendency of HNSCC for the population of
Taiwan. We observed that only the T/T genotype (C46359T) was found to be present in both patient
and control groups (100% frequency). The alleles frequency of −283CC, −283CT and −283TT among
patients and controls was, respectively, 88.1% versus 84.3%, 11.9% versus 15.3%, and 0% versus
0.4%. The allele −597GG was not found in both groups, whereas the allele frequency of −597TT and
−597GT for patients and controls was, respectively, 88.1% versus 85.5%, and 11.9% versus 14.5%. For
both DNMT3B SNPs, inter-group comparison of the allele frequency between patients and controls
and distribution of SNPs among cancer patients either featuring or not featuring cervical metastasis
did not reveal any significant difference. In conclusion, the relative distribution of three DNMT3B
SNPs among a Taiwanese population can not be used as a stratification marker to predict either an
individual’s susceptibility to HNSCC and/or the likelihood of cervical metastasis of HNSCC.
9- Patient and tumour factors associated with advanced carcinomas of the head and
neck Original Research Article
Oral Oncology, Volume 41, Issue 3, March 2005, Pages 313-319
Debbie M. Tromp, Xavier D.R. Brouha, Gert-Jan Hordijk, Jacques A.M. Winnubst, Rob J. de
Leeuw
Summary
This study identifies patient and tumour related factors associated with advanced carcinoma of the
head and neck. Special attention was paid to the role of patient and professional diagnostic delays.
Three-hundred and six patients newly diagnosed with carcinoma of the pharynx, larynx and oral
cavity were included in the study. Logistic regression analyses were used to identify the risk factors
for presenting with an advanced tumour. Multivariate analysis found that having a pharyngeal
carcinoma (OR 22.68; p = .000), an oral carcinoma (OR 6.51; p = .000), or a supraglottic carcinoma
(OR 8.12; p = .000), patient delay >3 months (OR 3.47; p = .001) and having a doctors’ contact for
another reason than the head and neck symptom (OR 0.20; p = .022) were predictive of presenting
with an advanced tumour. These results suggest that beyond tumour-related factors, the patients’
care seeking behaviour contributes to an increased risk of being diagnosed with an advanced tumour
of the head and neck.
10- Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell
carcinoma Original Research Article
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Cancer Letters, Volume 248, Issue 2, 18 April 2007, Pages 269-279
Mark G. Slomiany, Leigh Ann Black, Megan M. Kibbey, Melissa A. Tingler, Terry A. Day,
Steven A. Rosenzweig
Abstract
Abstract
IGF-1 receptor (IGF-1R) signaling is associated with increased tumorigenesis of epithelial cancers. In
light of recent epidemiological studies correlating high circulating levels of IGF-1 with increased risk
of second primary tumors (SPTs) of the head and neck, we examined IGF system and epidermal
growth factor receptor (EGFR) expression in human head and neck squamous cell carcinoma (HNSCC)
matched pairs and a cross-section of HNSCC cell lines. Employing the latter, we demonstrated that
IGF-1 stimulated S-phase transition in a PI 3-K/Akt and Erk-dependent manner in 5 of 8 cell lines, with
Erk activation being dependent upon EGFR kinase activity. IGF-1 stimulated thymidine incorporation
was inhibited by treatment with IGFBP-3, the IGF-1R tyrosine kinase inhibitor NVP-AEW541, or the
EGFR tyrosine kinase inhibitor AG1478. Combining IGFBP-3 with NVP-AEW541 or AG1478 abrogated
IGF-1 responses at 10-fold lower doses than either compound alone. These results demonstrate the
potential for co-targeting the IGF system and EGFR in HNSCC.
11- ADH1B and ALDH2 polymorphisms and their associations with increased risk of squamous
cell carcinoma of the head and neck in the Korean population Original Research Article
Oral Oncology, In Press, Corrected Proof, Available online 14 May 2011
Yong Bae Ji, Kyung Tae, Tae Hwan Ahn, Seung Hwan Lee, Kyung Rae Kim, Chul Won Park,
Byung Lae Park, Hyoung Doo Shin
Close preview |
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Abstract
Summary
Alcohol consumption is a major risk factor for squamous cell carcinoma of the head and neck
(SCCHN). Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are key enzymes in
ethanol metabolism. The objective of this study was to investigate the relationships of ADH and
ALDH single nucleotide polymorphisms (SNPs) with the risk of developing SCCHN in a Korean sample.
We genotyped ADH1B +3170A>G (rs1229984) and ALDH2 +1951G>A (rs671) SNPs in 225 Korean
SCCHN patients and 301 healthy controls by single base extension and TaqMan assay. The
frequencies of the ADH1B +3170A>G (*2*2/*2*1/*1*1) genotypes were 48.0%/38.7%/13.3% in SCCHN
patients, and 57.8%/37.2%/5.0% in controls, respectively. The odds ratio (OR) and 95% confidence
interval of the ADH1B *1*1 genotype was 1.89 (1.23–2.92) relative to the *2*2 genotype. The
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FACTEURS DE RISQUES EPIDEMIOLOGIE
frequencies of the ALDH2 +1951G>A (*1*1/*1*2/*2*2) genotypes were 67.6%/31.6%/0.9% in SCCHN
patients, and 67.8%/29.6%/2.7% in controls, respectively. In subgroup analyses according to smoking
and alcohol drinking status, the OR of the ADH1B *1*1 genotype was increased in the heavy drinker
group [8.85 (1.095–40.0)] and in the heavy smoker group [4.7 (1.54–14.29)]. We conclude that the
ADH1B *1*1 genotype is associated with an increased risk of SCCHN, especially in heavy drinkers and
heavy smokers. This genotype could be a useful biomarker for identifying Koreans with a greater risk
of SCCHN.
12- Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3353-61.
Active and involuntary tobacco smoking and upper aerodigestive tract cancer risks in a
multicenter case-control study.
Lee YC, Marron M, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, Lagiou P, Trichopoulos D,
Agudo A, Castellsague X, Bencko V, Holcatova I, Kjaerheim K, Merletti F, Richiardi L, Macfarlane GJ,
Macfarlane TV, Talamini R, Barzan L, Canova C, Simonato L, Conway DI, McKinney PA, Lowry RJ,
Sneddon L, Znaor A, Healy CM, McCartan BE, Brennan P, Hashibe M.
Source
IARC, Lyon, France.
Abstract
INTRODUCTION:
Several important issues for the established association between tobacco smoking and upper
aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by
type of tobacco, and among never alcohol drinkers and the associations with involuntary smoking
among nonsmokers. Our aim was to examine these specific issues in a large-scale case-control study
in Europe.
METHODS:
Analysis was done on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the AlcoholRelated Cancers and Genetic Susceptibility in Europe project, a multicenter case-control study in 10
European countries. Unconditional logistic regression was done to obtain odds ratios (OR) and 95%
confidence intervals (95% CI).
RESULTS:
Compared with never tobacco smoking, current smoking was associated with UADT cancer risks (OR,
6.72; 95% CI, 5.45-8.30 for overall; OR, 5.83; 95% CI, 4.50-7.54 for oral cavity and oropharynx; OR,
12.19; 95% CI, 8.29-17.92 for hypopharynx and larynx; and OR, 4.17; 95% CI, 2.45-7.10 for
esophagus). Among never drinkers, dose-response relationships with tobacco smoking pack-years
were observed for hypopharyngeal and laryngeal cancers (P(trend) = 0.010) but not for oral cavity and
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FACTEURS DE RISQUES EPIDEMIOLOGIE
oropharyngeal cancers (P(trend) = 0.282). Among never smokers, ever exposure to involuntary
smoking was associated with an increased risk of UADT cancers (OR, 1.60; 95% CI, 1.04-2.46).
CONCLUSION:
Our results corroborate that tobacco smoking may play a stronger role in the development of
hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never
drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health
interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence.
13- J Cancer Res Clin Oncol. 2007 Sep;133(9):673-8. Epub 2007 May 8.
Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic
prospective multicenter study.
Koskinen WJ, Brøndbo K, Mellin Dahlstrand H, Luostarinen T, Hakulinen T, Leivo I, Molijn A, Quint
WG, Røysland T, Munck-Wikland E, Mäkitie AA, Pyykkö I, Dillner J, Vaheri A, Aaltonen LM.
Source
Department of Virology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21,
00014 Helsinki, Finland. [email protected]
Abstract
PURPOSE:
Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal
squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumorcell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence.
Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux
disease (GERD) were evaluated
METHODS:
Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were
investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the
study. HPV DNA was determined with MY09/11 and GP5+
+/6+
+ nested PCR and SPF10 PCR
hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire
concerning risk factors was filled in.
RESULTS:
Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking
was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis.
Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated
with survival, although it correlated with heavy drinking.
CONCLUSION:
In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and
promoted early carcinogenesis.
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FACTEURS DE RISQUES EPIDEMIOLOGIE
14- Eur J Cancer Prev. 2009 Feb;18(1):76-84.
Alcoholrelated cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and
data collection.
Lagiou P, Georgila C, Minaki P, Ahrens W, Pohlabeln H, Benhamou S, Bouchardy C, Slamova A,
Schejbalova M, Merletti F, Richiardi L, Kjaerheim K, Agudo A, Castellsague X, Macfarlane TV,
Macfarlane GJ, Talamini R, Barzan L, Canova C, Simonato L, Lowry R, Conway DI, McKinney PA, Znaor
A, McCartan BE, Healy C, Nelis M, Metspalu A, Marron M, Hashibe M, Brennan PJ.
Source
Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece.
Abstract
Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than
nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are
established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely
causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors,
however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as
well as the exact nature of the implicated dietary variables, has not been clarified. To address these
issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers
and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11
European countries. Information and biological data from a total of 2304 cases and 2227 controls have
been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms
of 76 genes are being studied for genetic associations with UADT cancers. We report here the
methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and
controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males
and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common
subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of
UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol
drinkers among UADT cases compared with controls was observed.
15- Am J Epidemiol. 2007 Apr 1;165(7):814-20. Epub 2007 Jan 22.
Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the
supraglottis and glottis in Central Europe.
Hashibe M, Boffetta P, Zaridze D, Shangina O, Szeszenia-Dabrowska N, Mates D, Fabiánová E, Rudnai
P, Brennan P.
Source
International Agency for Research on Cancer, Lyon, France.
Abstract
Incidence rates for laryngeal cancer in Central Europe are among the highest in the world. The authors
recruited cases and controls between 2000 and 2002 for the Central and Eastern Europe Multicenter
Study to investigate the role of tobacco and alcohol as causes of laryngeal cancer in this region. A total
of 384 incident squamous cell cases were included, comprising 254 glottic and 108 supraglottic
cancers. Hospital controls were chosen from within the same catchment area, from diseases unrelated
to tobacco or alcohol (n = 918). Significant dose-response trends for frequency and duration of
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FACTEURS DE RISQUES EPIDEMIOLOGIE
tobacco use were observed for both supraglottic and glottic cancers, with potentially a more important
effect for supraglottic cancer. Quitting smoking was protective against laryngeal cancers after 5 years.
Any increases in risk for alcohol drinking were generally moderate and nonsignificant. A greater than
multiplicative interaction was observed between tobacco and alcohol on the risk of laryngeal cancer (p
= 0.04). Approximately 87% of laryngeal cancer cases in Central Europe are attributable to tobacco
use, of which 75% and 12% are due to current and past smoking, respectively. Approximately 39% are
attributable to the interaction between alcohol and tobacco. Preventive efforts to encourage current
smokers to quit are likely to be the most effective way to reduce the incidence of laryngeal cancer in
this region.
16- Oral Oncol. 2009 Jan;45(1):85-9. Epub 2008 May 19.
Diet diversity and the risk of laryngeal cancer: a case-control study from Italy and
Switzerland.
Garavello W, Lucenteforte E, Bosetti C, Talamini R, Levi F, Tavani A, Franceschi S, Negri E, La Vecchia
C.
Source
Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milan, Italy.
Abstract
Diet diversity (defined as the number of different foods consumed) has been considered an indicator of
a healthy diet, and favorably related to the risk of several digestive tract cancers. We analyzed the
relation between diet diversity and the risk of laryngeal cancer using data from a case-control study
carried out between 1992 and 2000 in Italy and Switzerland. The subjects of the study were 527
patients with histologically confirmed incident cancers of the larynx and 1297 patients admitted for
acute, non-neoplastic diseases, unrelated to tobacco or alcohol consumption. Total diversity was
computed as the number of different foods (overall and within four food groups, i.e., vegetables, fruit,
meat, and cereals) consumed at least once per week. A significant inverse association was observed for
vegetable diversity (OR=0.41, 95% CI: 0.28-0.59, for the highest versus the lowest quartile) and fruit
diversity (OR=0.40, 95% CI: 0.27-0.59). Conversely, a direct association was found for meat diversity
(OR=1.67, 95% CI: 1.11-2.50), while no meaningful association was found for total diet and cereal
diversity. The results were consistent across strata of age, alcohol drinking and tobacco smoking. This
study suggests that a diet not only rich but also varied in fruit and vegetables is related to a decreased
risk of laryngeal cancer risk.
17- Oral Oncol. 2009 Aug;45(8):e49-53. Epub 2009 Feb 28.
Dietary patterns and risk of oral cancer: a factor analysis study of a population in Jakarta,
Indonesia.
Amtha R, Zain R, Razak IA, Basuki B, Roeslan BO, Gautama W, Purwanto DJ.
Source
Oral Medicine Department, Trisakti University, Kyai Tapa, Grogol, Jakarta Barat, Indonesia.
[email protected]
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Abstract
A matched case-control, hospital-based study of oral cancer was conducted in Jakarta population. The
sample included 81 cases and 162 controls. The purpose of this study was to determine the association
between dietary pattern and oral cancer in a Jakarta population using factor analysis. Dietary data were
collected using food frequency questionnaire and factor analysis was performed on 15 food groups
resulting in four principle factors/components being retained. The first factor "preferred" was
characterized by fast food, fermented food, canned food, snacks high in fat and sugar, cooked and raw
vegetables, and seafood. The second factor labeled "combination" was loaded by the intake of dairy
product, red meat, white meat and fruits. The third factor labeled "chemical related was loaded by
processed food and monosodium glutamate and the fourth principle component consisted of drinks
and grain was labeled as "traditional". The conditional logistic regression was done using STATA 8 to
obtain the odds ratio (OR) of highest tertile of each component retained from factor analysis and the
ORs were then adjusted with risk habits. The consumption the highest tertile of the "preferred" pattern
increased the risk of oral cancer by two-times compared to the lowest tertile of consumption [adjusted
odds ratio (aOR)=2.17; 95% confidence interval (CI)=1.05-4.50]. The chemical related" pattern
showed higher risk of about threefold (aOR=2.56; 95% CI=1.18-5.54), while the "traditional" pattern
showed an increased of risk by twofold (aOR=2.04; 95% CI=1.01-4.41). In contrast, the
"combination" pattern displayed protective effects in relation to oral cancer (aOR=0.50; 95% CI=0.241.00). This finding suggests that factor analysis may be useful to determine the diet pattern of a big set
of food type and establish the correlation with oral cancer.
18- Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in
head and neck cancer Original Research Article
Cancer Epidemiology, Volume 34, Issue 5, October 2010, Pages 587-592
K. Sabitha, M. Vishnuvardhan Reddy, Kaiser Jamil
Abstract
Background: CYP1A1 is one of the commonest genes which had been widely investigated to find the
risk of various malignancies in different ethnic groups. The polymorphism in these genes with a
combination of environmental exposure has been hypothesized to confer a differential risk of cancer
for individuals carrying these genetic variants. Based on this model, individuals with higher CYP1A1
activity would be at increased risk of cancer when exposed to high levels of smoke components. The
proposed mechanism involves cytochrome P450 1A1 (CYP1A1), a gene that is inducible by
xenobiotics to produce genetic susceptibility for malignancies. Patients and procedures: We
performed a case–control study in 205 cases with histopathologically confirmed squamous cell
carcinoma of head and neck and reported habits of bidi or cigarettes smoking and 245 similar
controls to investigate the role of CYP1A1 polymorphisms in the risk of head and neck cancers
especially among smokers of Hyderabad Indian population. Venous blood samples (5 ml) were
collected from patients and control groups; genomic DNA was extracted and used for polymerase
chain reaction (PCR) to determine the genotypes. RFLP assays were designed to detect each of the
variant CYP1A1 alleles. Results and discussion: CYP1A1m1/m1 genotype (OR = 8.12, 95% CI: 3.27–
21.30) and CYP1A1w1/m1 showed elevated risk when compared with CYP1A1w1/w1. Similarly
CYP1A1w2/m2 (OR = 1.58, 95% CI: 0.94–2.67) and CYP1A1m2/m2 (OR = 6.31, 95% CI: 2.74–18.69)
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FACTEURS DE RISQUES EPIDEMIOLOGIE
genotypes also showed elevated risk when compared with CYP1A1w2/w2 genotype. This data
demonstrated that smoking was a risk factor for head and neck cancers. The m2 mutations were in
close linkage disequilibrium with the m1 mutations; 53% m1 mutants had the mutation in the m2
site. Conclusion: Those individuals carrying at least one CYP1A1 m1 or m2 variant allele were at a 2fold elevated risk for head and neck cancer. Our data clearly demonstrates that CYP1A1 is an
important determinant in susceptibility to tobacco-induced head and neck carcinogens and there is
an association between genetic polymorphism in the CYP1A1 locus and elevated risk of the type of
smoking among Indians. This appears to be a new and important prognostic and diagnostic marker
for determining the risk of head and neck cancers genetically.
19- Spectra of antinuclear antibodies in patients with squamous cell carcinoma of the lung and
of the head and neck Original Research Article
Cancer Detection and Prevention, Volume 29, Issue 1, 2005, Pages 59-65
Félix Fernández Madrid, Robert L. Karvonen, John Ensley, Michael Kraut, José L. Granda,
Huda Alansari, Naimei Tang, John E. Tomkiel
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Abstract
Abstract
Squamous cell carcinoma of the head and neck (HNSCC) and of the lung (LSCC) share some important
risk factors, but differ substantially in terms of prognosis and treatment. A pulmonary nodule
developing in patients with surgically cured HNSCC may pose a diagnostic dilemma. Markers able to
distinguish these two common malignancies would be of major clinical importance. In this work we
compared the spectrum of antinuclear antibodies (ANA) from 22 patients with SCCL to that of 40
patients with HNSCC. Patient sera were used to probe immunoblots of nuclear extracts from all four
major lung cancer cell types, normal lung fibroblasts, cells cultured from a HNSCC, and keratinocytes
cultured from the field cancerization. The ability to classify retrospectively LSCC from HNSCC based
on serum ANA reactivities was determined by recursive partitioning analyses. We found that while
both malignancies share reactivities to a small group of nuclear antigens, other reactivities are
directed against proteins uniquely or preferentially expressed in either SCCL or in SCCHN cells. Our
work shows that autoimmunity is a prominent feature of squamous cell carcinoma and suggests that
molecular characterization of nuclear antigens recognized by ANAs may lead to the discovery of
markers valuable to distinguish LSCC from HNSCC.
20- Effect of family history of cancers and environmental factors on risk of nasopharyngeal
carcinoma in Guangdong, China Original Research Article
Cancer Epidemiology, Volume 34, Issue 4, August 2010, Pages 419-424
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Ze-Fang Ren, Wen-Sheng Liu, Hai-De Qin, Ya-Fei Xu, Dan-Dan Yu, Qi-Sheng Feng, Li-Zhen
Chen, Xiao-Ou Shu, Yi-Xin Zeng, Wei-Hua Jia
Abstract
Background: Family history of nasopharyngeal carcinoma (NPC) is an established risk factor for this
cancer, but the contributions of family history of other types of cancer and its interaction with
environmental factors have not been well characterized. Methods: A total of 1845 incident cases of
NPC and 2275 matched controls from Guangdong, China were included in this study. Odds ratios (OR)
and 95% confidence intervals (CI) were calculated from logistic regression models adjusted for
smoking, consumption of alcohol, salted fish consumption, and demographic factors. Results: A
significant association between the risk of NPC and family history of any cancers in first degree
relatives was observed, and higher number of affected family member was related to a higher risk
(Ptrend < 0.01). Family history of NPC was the strongest predictor for NPC (OR: 3.35, 95% CI: 2.46–4.55
for all first degree relatives). The risk of NPC was also positively associated with history of head and
neck cancer among parents and lung and breast cancers among siblings. The combination of family
history of cancer, especially NPC, and the consumption of salt-preserved fish significantly increased
the risk for NPC. Conclusions: These results confirm that the risk for NPC increases with family history
of NPC and suggest that lung and breast cancer contribute to risk for NPC. A possible interaction
between family history of cancer, especially NPC, and consumption of salt-preserved fish in the
development of NPC was also identified.
21- Expression of haptoglobin predicts recurrence in head and neck squamous cell
carcinoma Original Research Article
Clinica Chimica Acta, Volume 411, Issues 15-16, 5 August 2010, Pages 1116-1121
Ching-Chih Lee, Hsu-Chueh Ho, Moon-Sing Lee, Shih-Kai Hung, Chih-Chia Yu, Yu-Chieh Su
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Abstract
Abstract
Background
We determined whether expression of haptoglobin by head and neck squamous cell carcinoma
(HNSCC) cells is associated with prognosis.
Methods
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Western blotting was carried out to investigate the expression of haptoglobin in oral cancer cell lines.
We study patients with HNSCC without distant metastasis at diagnosis. Correlation between cellular
haptoglobin and clinical characteristics of HNSCC was analyzed to assess the prognostic value of
cellular haptoglobin level. Kaplan–Meier survival curves and log-rank test were used to evaluate
differences in recurrence, distant metastasis, and overall survival rates between patients grouped
according to cellular haptoglobin level in cancer tissues. The relationship of haptoglobin expression
with survival was assessed using Cox proportional hazard models.
Results
Western blotting analysis showed that haptoglobin protein was expressed in 4 oral cancer cell lines.
The recurrence rate was higher in HNSCC patients with over-expression of haptoglobin (> 50%)
(P = 0.045). Over-expression of haptoglobin was also associated with an increased risk for recurrence
(hazard ratio [HR] 3.2; 95% confidence interval [CI], 1.127–8.895; P = 0.029) after adjusting for age,
gender, disease site, stage, and treatment modality.
Conclusions
Altogether, the data presented show that cellular expression of haptoglobin is closely related to
recurrence rate in HNSCC patients. The elevated risk of relapse was confirmed in a multivariate
analysis. The cellular expression of haptoglobin may be a prognostic factor in HNSCC.
22- Future challenges in head and neck cancer: From the bench to the bedside? Review Article
Critical Reviews in Oncology/Hematology, In Press, Corrected Proof, Available online 9
December 2010
Luca Calabrese, Angelo Ostuni, Mohssen Ansarin, Gioacchino Giugliano, Fausto Maffini,
Daniela Alterio, Maria Cossu Rocca, Giuseppe Petralia, Roberto Bruschini, Fausto Chiesa and
on behalf of AROME
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Abstract
Abstract
HNC is the 11th most frequent carcinoma with a world-wide yearly incidence exceeding over half a
million cases [1], a 10:1 male gender predilection and country specific variability [2]. The principal
risk factors are tobacco and alcohol use and, in a growing population without these exposures, HPV
infection.
While much progress has been made in understanding the molecular basis of cancer, the 5-year
mortality of head and neck cancer has remained approximately 50%. To this date we have not been
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FACTEURS DE RISQUES EPIDEMIOLOGIE
able to translate as much of our basic science knowledge into significant disease altering therapeutic
strategies in terms of local, loco-regional, functional and overall survival. Challenges remain in all
aspects of head and neck cancer management: prevention, diagnosis, surgical and non-surgical
treatment.
23- Head Face Med. 2006 Oct 16;2:33.
Circulating immune complexes and trace elements (Copper, Iron and Selenium) as
markers in oral precancer and cancer : a randomised, controlled clinical trial.
Khanna SS, Karjodkar FR.
Source
Department of Oral Medicine and Radiology, Nair Hospital Dental College, Mumbai, India.
[email protected]
Abstract
AIM:
To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in
serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell
carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for
disease occurrence and progression.
METHODS:
Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG)
serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the
Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic
Stripping Voltametry respectively.
RESULTS:
The data analysis revealed increased circulating immune complex levels in the precancer and cancer
patients. Serum copper levels showed gradual increase from precancer to cancer patients. However,
serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked
decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the
occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order.
CONCLUSION:
The present study shows that these immunological and biological markers may be associated with the
pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts
would, therefore, help in early detection, management, and monitoring the efficacy of treatment.
24- Diversité des modèles d’évolution des incidences : implication en
cancérogenèse ? Original Research Article
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FACTEURS DE RISQUES EPIDEMIOLOGIE
Revue des Maladies Respiratoires, Volume 28, Issue 1, January 2011, Pages 41-50
G. Buiret, G. Launoy, L. Remontet, N. Bossard, J. Iwaz, A. Belot, R. Ecochard
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Abstract
Résumé
Objectif
Les cancers ORL, bronchiques et œsophagiens sont principalement liés à la consommation d’alcool
et/ou de tabac. L’incidence des cancers ayant les mêmes facteurs de risque devrait varier de façon
similaire dans le temps et l’espace. Le but de cette étude était d’identifier des groupes de cancers
ayant la même évolution spatiotemporelle.
Méthodes
Cinquante mille neuf cent quatre-vingt cas de dix types de cancers différents ont été recueillis entre
1982 et 2002 dans six départements français. Les niveaux d’incidence et leur tendance évolutive ont
été analysés en utilisant un modèle âge–cohorte avec un effet aléatoire qui prenait en compte
l’hétérogénéité entre départements.
Résultats
Trois groupes de cancers ayant une évolution similaire de l’incidence spatiotemporelle ont été
identifiés : (1) cavité orale, oropharynx, hypopharynx, larynx, œsophage et carcinomes épidermoïdes
bronchiques dont les incidences diminuaient uniformément ; (2) adénocarcinomes bronchiques et
autres histologies bronchiques dont les incidences augmentaient uniformément ; (3) carcinomes
bronchiques à grandes et à petites cellules dont l’évolution des incidences spatiotemporelles était très
hétérogène.
Conclusion
Par l’utilisation de méthodes d’épidémiologie descriptive, différents groupes de cancers ont été
individualisés. Cette diversité pourrait suggérer des latences et des sensibilités différentes vis-à-vis des
carcinogènes.
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