Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Gene-Environment Epidemiology Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69008 Lyon, France.
Journal of the National Cancer Institute (Impact Factor: 12.58). 06/2007; 99(10):777-89. DOI: 10.1093/jnci/djk179
Source: PubMed


At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor.
We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case-control studies that included 10,244 head and neck cancer case subjects and 15,227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided.
Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose-response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx.
Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.

Download full-text


Available from: José Eluf-Neto,
53 Reads
  • Source
    • "Similar observations were reported for the combination of spliceostatin A (structurally similar to meayamycin B) and ABT-737 in neuroblastoma25. Given the mutual risk factors, such as alcohol and cigarette consumption, shared between non-small cell lung carcinoma and HNSCC2627, we reasoned that meayamycin B might also prime HNSCC cells for ABT-737. Therefore, we wished to examine the anticancer activity of meayamycin B, as a single-agent or in combination with ABT-737. "
    [Show abstract] [Hide abstract]
    ABSTRACT: ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL-XL. Meayamycin B switches the splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1 (SF3B1) with meayamycin B promotes the generation of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1-L). This action was previously associated with the cytotoxicity of meayamycin B in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in response to an ablation of MCL1-L by meayamycin B. In this study, we further exploited this synergistic combination in head and neck squamous cell carcinoma (HNSCC), up to 90% of which overexpress MCL1 and BCL-XL. In a panel of seven HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC against each agent alone. Both RT-PCR and Western blotting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non-oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced tumorigenesis.
    Scientific Reports 08/2014; 4:6098. DOI:10.1038/srep06098 · 5.58 Impact Factor
  • Source
    • "In addition, smoking status, frequency, and duration all appear to be of importance in the association between cigarette smoking and risk of HNC overall, OHPC, and LC. These results are generally consistent with previous reviews showing that cigarette smoking has a stronger effect on the larynx and/or pharynx than on the oral cavity [7,8,10,23,41]; in two meta-analyses, the larynx seemed to be clearly most susceptible to the effects of cigarette smoking [23,41]. A possible explanation for this could be the aerodynamics of respiratory flow in the upper airway: this flow changes from laminar in the oral cavity to turbulent in the larynx, which may result in the larynx and pharynx having a higher exposure to inhaled air - and thus to cigarette smoke - than the oral cavity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prospective data on alcohol consumption, cigarette smoking and risk of head-neck cancer (HNC) subtypes, i.e. oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), are limited. We investigated these associations within the second largest prospective study on this topic so far, the Netherlands Cohort Study. 120,852 participants completed a questionnaire on diet and other cancer risk factors in 1986. After 17.3 years of follow-up, 395 HNC (110 OCC, 83 OHPC, and 199 LC) cases and 4288 subcohort members were available for case-cohort analysis using Cox proportional hazards models. For total HNC, the multivariable adjusted incidence rate ratio (RR) was 2.74 (95% confidence interval (CI) 1.85-4.06) for those drinking >=30g ethanol/day compared with abstainers; in subtypes, RRs were 6.39 for OCC, 3.52 for OHPC, and 1.54 for LC. Compared with never cigarette smokers, current cigarette smokers had a RR of 4.49 (95%CI 3.11-6.48) for HNC overall, and 2.11 for OCC, 8.53 for OHPC, and 8.07 for LC. A significant, positive, multiplicative interaction between categories of alcohol consumption and cigarette smoking was found for HNC overall (P interaction 0.03). Alcohol consumption and cigarette smoking were independently associated with risk of HNC overall, with a positive, multiplicative interaction. The strength of these associations differed among HNC-subtypes: OCC was most strongly associated with alcohol consumption but most weakly with cigarette smoking, whereas LC was not statistically significantly associated with alcohol consumption.
    BMC Cancer 03/2014; 14(1):187. DOI:10.1186/1471-2407-14-187 · 3.36 Impact Factor
  • Source
    • "Individuals who smoke more than 20 cigarettes a day and consume more than 100 g of alcohol a day are believed to be at increased risk for oral epithelial dysplasia.27 In addition, alcohol has been found to be an independent risk factor for OCSCC among non-smokers and tobacco smoke in non-drinkers.28 Moreover, both factors together seem to enhance the carcinogenic effect. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is a disease of middle-aged to elderly adults. However, an increased incidence of HNSCC in young people under 45 years of age has been reported recently. In the present review, we focused on the epidemiology and aetiology of HNSCC in adults under 45 years of age. We reviewed literature related to HNSCC in adult patients less than 45 years of age and discussed current treatment options and prognosis. HNSCC in young adults is associated with a higher incidence rate in nonsmokers, lower female-to-male ratio, a higher percentage of oral cavity and oropharynx tumours, and fewer second primary tumours. However, aside from traditional risk factors of tobacco and alcohol exposure, the causes of these cancers in young adults remain unclear. Agents that might contribute to risk include infection with high-risk human papillomavirus subtypes as well as genetic factors or immunodeficiency status. The expected increase in incidence and mortality of the young with HNSCC may become a major public health concern if current trends persist, particularly lifestyle habits that may contribute to this disease. Given the younger age and potential long-term adverse sequelae of traditional HNSCC treatments, young adults should be treated on a case-by-case basis and post-therapy quality of life must be considered in any treatment-decision making process.
    Radiology and Oncology 03/2014; 48(1):1-10. DOI:10.2478/raon-2013-0057 · 1.91 Impact Factor
Show more