Biomedical subjects

Paolo Boffetta

Publications and source records attributed to Paolo Boffetta.

At least 55 records · Page 3Linked to original sources

PubMed2006

Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium.

BACKGROUND: Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). METHODS: We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. FINDINGS: The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083). INTERPRETATION: Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.

Case-Control Studies↗

PubMed2006

Alcohol and cancer.

A causal association has been established between alcohol consumption and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colon, rectum, and, in women, breast; an association is suspected for cancers of the pancreas and lung. Evidence suggests that the effect of alcohol is modulated by polymorphisms in genes encoding enzymes for ethanol metabolism (eg, alcohol dehydrogenases, aldehyde dehydrogenases, and cytochrome P450 2E1), folate metabolism, and DNA repair. The mechanisms by which alcohol consumption exerts its carcinogenic effect have not been defined fully, although plausible events include: a genotoxic effect of acetaldehyde, the main metabolite of ethanol; increased oestrogen concentration, which is important for breast carcinogenesis; a role as solvent for tobacco carcinogens; production of reactive oxygen species and nitrogen species; and changes in folate metabolism. Alcohol consumption is increasing in many countries and is an important cause of cancer worldwide.

Alcohol Drinking↗

PubMed2006

A road map for efficient and reliable human genome epidemiology.

Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.

Databases, Factual↗

PubMed2006

Lung cancer and occupation in nonsmokers: a multicenter case-control study in Europe.

BACKGROUND: Tobacco smoking is the main cause for lung cancer worldwide, making it difficult to examine the carcinogenic role of other risk factors because of possible confounding by smoking. Therefore, the present study aimed to investigate the association between lung cancer and occupation independent of smoking. METHODS: A case-control study of lung cancer was carried out between March 1998 and January 2002 in 16 centers from 7 European countries, including 223 never-smoking cases and 1039 controls. Information on lifestyle and occupation was obtained through detailed questionnaires. Job and industries were classified as entailing exposure to known or suspected carcinogens; in addition, expert assessment provided exposure estimates to specific agents. RESULTS: The odds ratio of lung cancer among women employed for more than 12 years in suspected high-risk occupations was 1.75 (95% confidence interval = 0.63-4.85). A comparable increase in risk was not detected for employment in established high-risk occupations or among men. Increased risk of lung cancer was suggested among individuals exposed to nonferrous metal dust and fumes, crystalline silica, and organic solvents. CONCLUSION: Occupations were found to play a limited role in lung cancer risk among never-smokers. Jobs entailing exposure to suspected lung carcinogens should receive priority in future studies among women. Nonferrous metal dust and fumes and silica may exert a carcinogenic effect independently from smoking.

Case-Control Studies↗

PubMed2006

Cancer mortality among butchers: a 24-state death certificate study.

OBJECTIVE: The objective of this study was to document cancer mortality among American butchers. METHODS: Death certificates collected in 24 American states were used to calculate mortality odds ratios (ORs) and their confidence intervals (CIs) for 18,639 butchers. RESULTS: Butchers experienced an increased mortality of cancer of the oral cavity (OR, 1.40; 95% CI = 1.09-1.81), esophagus (OR, 1.19; 95% CI = 1.01-1.40), pharynx (OR, 1.22; 95% CI = 0.91-1.64), and larynx (OR, 1.19; 95% CI = 0.92-1.54), as well as a reduced mortality from melanoma (OR, 0.70; 95% CI = 0.52-0.94), non-Hodgkin lymphoma (OR, 0.82; 95% CI = 0.69-0.97), and breast cancer (OR, 0.76; 95% CI = 0.58-0.99). CONCLUSIONS: It is likely that occupational exposures experienced by butchers have contributed to the increased risk of cancers of the oral cavity and esophagus.

Adult↗

PubMed2006

Plasma C-reactive protein and risk of cancer: a prospective study from Greece.

BACKGROUND: Inflammation is an important component of carcinogenesis but little research has been conducted on whether inflammation markers can be predictive of cancer risk in humans. METHODS: We analyzed C-reactive protein (CRP), a marker of inflammation, in plasma samples of 496 cases of cancer and 996 controls selected among participants in a prospective study from Greece. RESULTS: Plasma CRP level was higher in cancer cases than controls (odds ratio for increase in CRP level of 3.2 mg/L, 1.20; 95% confidence interval, 1.10-1.32): The corresponding odds ratio after exclusion of the first year of follow-up and of individuals with CRP level above 20 mg/L was 1.32 (95% confidence interval, 1.15-1.52). Although based on small number of cases, the association between elevated plasma CRP level and risk was stronger for cancers of the liver, lung, skin, kidney, and bladder, as well as for lymphoma and leukemia than for other neoplasms. CONCLUSIONS: Our results confirm the important role of inflammation in human cancer and suggest that plasma CRP level is a potential marker of increased cancer risk.

Adult↗

PubMed2006

Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract.

BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.

Adult↗

PubMed2006

Statin use and risk of lymphoid neoplasms: results from the European Case-Control Study EPILYMPH.

BACKGROUND: Statins, drugs used to treat dyslipidemia, may have anticancer properties. We have evaluated lymphoma risk associated with regular statin use in an international case-control study. METHODS: This case-control study included 2,362 cases of incident B- and T-cell lymphoma from Czech Republic, France, Germany, Ireland, Italy, and Spain and 2,206 hospital or population controls. Information on drug use, diagnosis at admission (for hospital controls), and putative risk factors for lymphoma was collected with personal interviews. Hospital controls admitted for diseases possibly entailing use of statins were excluded from the analysis. RESULTS: The odds ratio for regular statin use was 0.61 (95% confidence interval, 0.45-0.84); all major lymphoma subtypes showed similarly decreased risks. Decreased risks were observed in all centers. Duration of statin use was not associated with a greater reduction in the risk of lymphoma. Use of other lipid lowering drugs, such as fibrates, did not significantly modify the risk of lymphoma (odds ratio, 0.75; 95% confidence interval, 0.44-1.27). CONCLUSION: Statin use was associated with an important reduction in lymphoma risk, adding to the growing evidence of anticancer properties of this group of drugs. These results are reassuring for the increasing number of patients taking statins on a regular basis.

Adult↗

PubMed2006

NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis.

UNLABELLED: NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, their less toxic form. A sequence variant at position 609 (C --> T) in the NQO1 gene encodes an enzyme with reduced quinone reductase activity in vitro and thus was hypothesized to affect cancer susceptibility. We conducted meta-analyses focusing on three cancer sites (lung, bladder, and colorectum) to summarize the findings from the current literature and to explore sources of heterogeneity. RESULTS: There is no clear association between the NQO1 Pro187Ser polymorphism and lung cancer risk in the three ethnic groups examined: odds ratio (OR(White)) C/T + T/T versus C/C = 1.04 [95% confidence interval (95% CI), 0.96-1.13], OR(Asian) = 0.99 (95% CI, 0.72-1.34), and OR(Blacks) = 0.95 (95% CI, 0.66-1.36). However, a modestly increased risk was suggested for the variant homozygotes in whites (OR T/T versus C/C, 1.19; 95% CI, 0.94-1.50). Analysis excluding one outlier study suggested the variant allele may be associated with reduced lung cancer risk in Asians. Meta-analyses for bladder and colorectal cancer suggested a statistically significant association with the variant genotypes in whites. In stratified analyses, the NQO1 Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians. CONCLUSIONS: Results from our meta-analyses suggest that the variant NQO1 Pro187Ser genotype may affect individual susceptibility to lung, bladder, and colorectal cancer. Such effects of the NQO1 polymorphism seem to be modified by ethnicity and smoking status.

Chi-Square Distribution↗

PubMed2006

Serum cotinine level as predictor of lung cancer risk.

BACKGROUND: No prospective studies are available on serum cotinine level as a marker of lung cancer risk. METHODS: We analyzed serum cotinine level among 1,741 individuals enrolled since the 1970s in a prospective study of Norwegian volunteers who developed lung cancer during the follow-up and 1,741 matched controls free from lung cancer. Serum cotinine was measured with a competitive immunoassay. Regression dilution was corrected for based on repeated measures on samples from 747 subjects. RESULTS: Mean serum cotinine level was higher in cases than in controls. Compared with subjects with a cotinine level of < or = 5 ng/mL, the odds ratio of lung cancer was increasing linearly, reaching 55.1 (95% confidence interval, 35.7-85.0) among individuals with a serum cotinine level of > 378 ng/mL. There was no clear suggestion of a plateau in risk at high exposure levels. Odds ratios were very similar in men and women. We found no association between serum cotinine level (range, 0.1-9.9 ng/mL) and lung cancer risk among self-reported nonsmokers and long-term quitters (79 cases and 350 controls). DISCUSSION: The association between tobacco smoking and lung cancer risk might be stronger than is estimated from questionnaire-based studies. Serum cotinine level is a predictor of risk of lung cancer among smokers. The reported plateau in risk at high doses is likely due mainly to artifacts. There is no difference between men and women in the carcinogenicity of tobacco smoking.

Biomarkers↗

PubMed2006

Cancer mortality in workers exposed to organochlorine compounds in the pulp and paper industry: an international collaborative study.

The objective of this study was to evaluate cancer mortality in pulp and paper industry workers exposed to chlorinated organic compounds. We assembled a multinational cohort of workers employed between 1920 and 1996 in 11 countries. Exposure to both volatile and nonvolatile organochlorine compounds was estimated at the department level using an exposure matrix. We conducted a standardized mortality ratio (SMR) analysis based on age and calendar-period-specific national mortality rates and a Poisson regression analysis. The study population consisted of 60,468 workers. Workers exposed to volatile organochlorines experienced a deficit of all-cause [SMR = 0.91; 95% confidence interval (CI), 0.89-0.93] and all-cancer (SMR = 0.93; 95% CI, 0.89-0.97) mortality, with no evidence of increased risks for any cancer of a priori interest. There was a weak, but statistically significant, trend of increasing risk of all-cancer mortality with increasing weighted cumulative exposure. A similar deficit in all-cause (SMR = 0.94; 95% CI, 0.91-0.96) and all-cancer (SMR = 0.94; 95% CI, 0.89-1.00) mortality was observed in those exposed to nonvolatile organochlorines. No excess risk was observed in cancers of a priori interest, although mortality from Hodgkin disease was elevated (SMR = 1.76; 95% CI, 1.02-2.82) . In this study we found little evidence that exposure to organochlorines at the levels experienced in the pulp and paper industry is associated with an increased risk of cancer, apart from a weak but significant association between all-cancer mortality and weighted cumulative volatile organochlorine exposure.

Humans↗

PubMed2005

Lifestyle habits as prognostic factors in survival of laryngeal and hypopharyngeal cancer: a multicentric European study.

Little information is available on the role of tobacco, alcohol and diet in the survival of upper aero digestive cancers. Our study analysed the survival of 931 laryngeal and hypopharyngeal cancer patients, enrolled in a population based case-control study conducted at 5 centres in southeast Europe during 1979-1982. Age at the time of diagnosis and site of origin of tumour were observed to be predictors of the survival. Cigarette smoking, and to a limited extent alcohol drinking, before the diagnosis of tumour seem to influence the overall survival whereas high intakes of vegetables and vitamin C were observed to favourably affect the prognosis. For mortality from upper aerodigestive cancer protective effects of high intakes of vegetables, fibres and vitamin C were observed. Our results support the hypothesis that there is a role for dietary intervention to improve survival of laryngeal and hypopharyngeal cancer patients.

Aged↗

PubMed2005

Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review.

Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to cancer risk. However, epidemiologic findings have been inconsistent. The authors conducted meta-analyses of associations between genes in the base excision repair pathway and cancer risk, focusing on three key genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1), and x-ray repair cross-complementing group 1 (XRCC1). They found increased lung cancer risk among subjects carrying the OGG1 Cys/Cys genotype (odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.01, 1.53), using 3,253 cases and 3,371 controls from seven studies; this is consistent with experimental evidence that this isoform exhibits decreased activity. They found a protective effect of the XRCC1 194Trp allele for tobacco-related cancers (OR = 0.86, 95% CI: 0.77, 0.95), using 4,895 cases and 5,977 controls from 16 studies; this is compatible with evidence of lower mutagen sensitivity for this allele. The XRCC1 399Gln/399Gln genotype was associated with increased risk of tobacco-related cancers among light smokers (OR = 1.38, 95% CI: 0.99, 1.94) but decreased risk among heavy smokers (OR = 0.71, 95% CI: 0.51, 0.99), suggesting effect modification by tobacco smoking. There was no association between cancer risk and the APE1/APEX1 Asp148Glu and XRCC1 Arg280His polymorphisms. Recommendations for future studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure.

Confidence Intervals↗

PubMed2005

The role of vegetable and fruit consumption in the aetiology of squamous cell carcinoma of the oesophagus: a case-control study in Uruguay.

There is strong evidence of a protection of high consumption of plant foods against squamous cell carcinoma of the oesophagus, but the respective role of fruits and vegetables is not well elucidated. In the time period 1996-2003, a case-control study designed in order to address this question was conducted in Uruguay. The study included 200 cases and 400 age- and sex-matched controls. High total vegetable and total fruit consumption was the strongest protective food group for this malignancy (OR 0.31, 95% CI 0.18-0.51). When this food group was dissected in total vegetables and total fruits, the latter item was more protective than the former one (OR for total fruits 0.48, 95% CI 0.35-0.66) (p-value for difference between both variables 0.04). Finally, when total fruits were dissected in citrus fruits and other fruits, citrus fruits were strongly associated with a reduction in risk (OR 0.47, 95% CI 0.34-0.67). The results of our study point towards an important role of fruits in the prevention of squamous cell carcinoma of the oesophagus.

Adult↗

PubMed2005

Is the risk of lung cancer reduced among eczema patients?

Persons with a history of eczema have been shown to have a reduced risk of lung cancer, but the evidence has been inconclusive because of the small size of previous studies and their limited ability to control for confounding by smoking. The objective of this study was to determine the role of eczema in relation to lung cancer while overcoming the limitations of previous investigations. Study subjects included 2,854 cases and 3,116 population and hospital controls recruited during 1998-2001 from 16 areas in the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and the United Kingdom. Odds ratios were calculated for self-reported history of eczema via multivariate logistic regression modeling. The odds ratio for a history of eczema was 0.61 (95% confidence interval: 0.48, 0.76) after control for age, sex, study center, and cumulative tobacco smoking. There was no heterogeneity in the results by sex or age at onset of eczema. Subjects reporting use of medication for eczema had a lower odds ratio than subjects not reporting such use. This study provides further evidence for an inverse association between history of eczema and lung cancer risk, which is unlikely to be due to chance, bias, or confounding.

Adult↗

PubMed2005

Perspectives on the molecular epidemiology of aerodigestive tract cancers.

Improving laboratory techniques and the greater availability of genetic data have led to a flurry of publications from molecular epidemiologic studies on aerodigestive tract cancers. Inconsistent results have been observed in studies of sequence variants, due to limitations such as small sample size, possible detection of false positives, moderate prior probabilities that each SNP confers a substantial increase in cancer risk, and publication bias. Meta- and pooled-analyses were shown to be effective in elucidating modest increases in aerodigestive tract cancer risk attributable to sequence variants. Phenotypic assays developed to quantify an individual's DNA repair capacity have been applied to epidemiological studies on aerodigestive tract cancers. Epigenetic events have also been studied in tumor progression and as susceptibility factors for aerodigestive tract cancers, in smaller scale studies. It is imperative that limitations of previous studies are addressed for future research in the molecular epidemiology of aerodigestive tract cancers. Some recommendations for future research are to: (i) incorporate multiple markers of different types (ex. genotype and phenotype data), (ii) enhance statistical power by conducting studies with larger sample size, and developing consortia to coordinate research efforts, (iii) improve marker selection via a hybrid strategy of incorporating data on evolutionary biology and physico-chemical properties of amino acids, with haplotype/tag SNP data, (iv) employ novel statistical methods such as hierarchical modeling with Bayesian adjustments, false positive reporting probability and modeling of complex pathways. Consortia have been initiated for head and neck cancer (International Head and Neck Cancer Epidemiology Consortium (INHANCE)) and lung cancer (International Lung Cancer Consortium (ILCCO)) with the aim to share comparable data, to focus on rare subgroups such as nonsmokers and to coordinate laboratory analyses. Such collaborative efforts and integration across disciplines will be essential in contributing to the elucidation of genetic susceptibility to aerodigestive tract cancers.

Carcinogens↗

PubMed2005

A network of investigator networks in human genome epidemiology.

The task of identifying genetic determinants for complex, multigenetic diseases is hampered by small studies, publication and reporting biases, and lack of common standards worldwide. The authors propose the creation of a network of networks that include groups of investigators collecting data for human genome epidemiology research. Twenty-three networks of investigators addressing specific diseases or research topics and representing several hundreds of teams have already joined this initiative. For each field, the authors are currently creating a core registry of teams already participating in the respective network. A wider international registry will include all other teams also working in the same field. Independent investigators are invited to join the registries and existing networks and to join forces in creating additional ones as needed. The network of networks aims to register these networks, teams, and investigators; be a resource for information about or connections to the many networks; offer methodological support; promote sound design and standardization of analytical practices; generate inclusive overviews of fields at large; facilitate rapid confirmation of findings; and avoid duplication of effort.

Databases, Genetic↗

PubMed2005

Lung cancer and indoor pollution from heating and cooking with solid fuels: the IARC international multicentre case-control study in Eastern/Central Europe and the United Kingdom.

Exposure to fuel from cooking and heating has not been studied in Europe, where lung cancer rates are high and many residents have had a long tradition of burning coal and unprocessed biomass. Study subjects included 2,861 cases and 3,118 controls recruited during 1998-2002 in the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and the United Kingdom. The odds ratio of lung cancer associated with solid fuel use was 1.22 (95% confidence interval (CI): 1.04, 1.44) for cooking or heating, 1.37 (95% CI: 0.90, 2.09) for solid fuel only for cooking, and 1.24 (95% CI: 1.05, 1.47) for solid fuels used for both cooking and heating. Risk increased relative to the percentage of time that solid fuel was used for cooking (p(trend) < 0.0001), while no risk increase was detected for solid fuel used for heating. The odds ratio of lung cancer in whole-life users of solid cooking fuel was 1.80 (95% CI: 1.35, 2.40). Switching to nonsolid fuels resulted in a decrease in risk. The odds ratio for the longest duration of time since switching was 0.76 (95% CI: 0.63, 0.92). The data suggest a modest increased risk of lung cancer related to solid-fuel use for cooking rather than heating.

Adult↗