Cohort studies have been central to the establishment of the known causes of cancer. To dissect cancer etiology in more detail-for instance, for personalized risk prediction and prevention, ...assessment of risks of subtypes of cancer, and assessment of small elevations in risk-there is a need for analyses of far larger cohort datasets than available in individual existing studies. To address these challenges, the NCI Cohort Consortium was founded in 2001. It brings together 58 cancer epidemiology cohorts from 20 countries to undertake large-scale pooling research. The cohorts in aggregate include over nine million study participants, with biospecimens available for about two million of these. Research in the Consortium is undertaken by >40 working groups focused on specific cancer sites, exposures, or other research areas. More than 180 publications have resulted from the Consortium, mainly on genetic and other cancer epidemiology, with high citation rates. This article describes the foundation of the Consortium; its structure, governance, and methods of working; the participating cohorts; publications; and opportunities. The Consortium welcomes new members with cancer-oriented cohorts of 10,000 or more participants and an interest in collaborative research.
Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 ...US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.
Background 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. Methods 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 10244 head and neck cancer case subjects and 15227 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. Results 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. Conclusions 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.
The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess ...head and neck cancer burden.
We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR).
A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America).
Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases.
Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the ...International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
Background Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). Methods We undertook a pooled analysis of four population-based and four ...hospital-based case–control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral–anal contact. Findings were stratified by sex and disease subsite. Results Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners OR = 1.25, 95% confidence interval (CI) 1.01, 1.54 and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). Conclusions Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.
There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, ...with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual‐level data from ten case–control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43–4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4–20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34‐3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41‐20.8%). Our project of a large pool of case–control studies supports a protective effect of total folate intake on OPC risk.
What's new?
Folate is essential to DNA synthesis and repair, suggesting that folate deficiency, in disrupting normal DNA processes, may facilitate the development of certain cancers, including oral and pharyngeal cancer (OPC). The relationship between folate intake and risk of OPC, however, is unclear. In this analysis of data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, high levels of folate intake were found to be inversely associated with overall OPC risk. The association was strongest for cancer of the oral cavity. Risk of OPC was highest among heavy alcohol drinkers with low folate levels.
The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual‐level pooled data from ten case‐control studies (5959 cases and 12,248 controls) ...participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non‐alcohol energy‐adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40–0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54–0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large‐scale pooled analysis suggest that, although in the presence of between‐study heterogeneity, a greater intake of fiber may lower HNC risk.
What's new?
Higher intake of fruit and vegetables is thought to lower the risk of HNCs. These foods are rich in phytochemicals and vitamins, but could dietary fiber also play a role in this protective effect? In this analysis, the authors pooled data from 10 separate studies to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Their results suggest that a greater intake of fiber may indeed lower HNC risk.
Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective ...mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual‐level pooled data from ten case‐control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study‐specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non‐alcohol energy‐adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45–0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40–0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.
What's new?
A diet rich in fruits and vegetables is thought to offer protection against head and neck cancers (HNC). However, it has not been clear which specific nutrients might play a role in this effect. In this re‐analysis of several previous studies, the authors found that a higher intake of vitamin C from natural sources was associated with a significantly lower risk of anatomical subsites of HNC.
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