Joshua E. Muscat

Interaction between tobacco and alcohol use and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer Epidemiology consortium

Background: 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. Methods: 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 (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 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). Conclusions: 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. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Colorectal Cancer Risk and Dietary Intake of Calcium, Vitamin D, and Dairy Products: A Meta-Analysis of 26,335 Cases From 60 Observational Studies

In vivo and in vitro studies suggest that dairy products, calcium, and dietary vitamin D inhibits the development of colorectal cancer (CRC). A meta-analysis was performed to evaluate this relationship in observational studies. Data from 60 epidemiological studies enrolling 26,335 CRC cases were pooled using a general variance-based meta-analytic method. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated for the highest vs. the lowest intake categories. Sensitivity analyses tested the robustness of these summary effect measures and the statistical heterogeneity. The summary RR for high milk and dairy product intake, respectively, on colon cancer risk was 0.78 (95% CI = 0.67–0.92) and 0.84 (95% CI = 0.75–0.95). Milk intake was unrelated to rectal cancer risk. High calcium intake had a greater protective effect against tumors of the distal colon and rectal cancer vs. proximal colon. The risk reduction associated with calcium was similar for dietary and supplemental sources. Vitamin D was associated with a nonsignificant 6% reduction in CRC risk. Higher consumption of milk/dairy products reduces the risk of colon cancer, and high calcium intake reduces the risk of CRC. Low vitamin D intake in the study populations may limit the ability to detect a protective effect if one exists.

Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium

BACKGROUND Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. METHODS Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. RESULTS Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, P(trend) = 2 x 10(-26)), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, P(trend) = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P(trend) = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P(trend) = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P(trend) = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. CONCLUSIONS In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

Tobacco, alcohol, asbestos, and occupational risk factors for laryngeal cancer.

Data from a hospital‐based case‐control study between 1985‐1990 were used to examine the effects of tobacco, alcohol, asbestos, and other occupational exposures on laryngeal cancer risk in 194 white men with primary cancer of the larynx and 184 age‐matched control subjects. A dose‐dependent effect for current cigarette smoking was observed, with higher relative risks (RR) for supraglottic cancer (RR, 21.6 to 68) than for cancer of the glottis (RR, 5.5 to 20.7). Elevated RR for ex‐smokers (RR, 4.8) and pipe and cigar smokers (RR, 4.3) did not vary by subsite. The effects of alcohol also showed dose‐dependent effects, with higher RR for cancer of the supraglottis than glottis for heavy drinkers (207 ml or more/daily; RR, 9.6 versus 2.5) and binge drinkers (RR, 28.4 versus 8.3). A slightly elevated but not significant association was seen for asbestos exposure and glottic cancer (RR, 1.3). The RR did not increase linearly with the number of years employed in asbestos‐related occupations. No relationship was observed between asbestos and cancer of the supraglottis. When examining the data for a synergistic effect of cigarette smoking and asbestos exposure, no excess risk was found. A significantly elevated risk was found for men exposed to diesel fumes (RR, 5.2). Elevated but not significant RR were seen for men chronically exposed to rubber (RR, 6.4) and wood dust or employed as construction laborers, auto mechanics, and other jobs. A significant inverse trend with body mass was observed for cancer of the supraglottis.

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

BACKGROUND Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. METHODS We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. RESULTS Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. CONCLUSIONS Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

Handheld cellular telephones and risk of acoustic neuroma

Abstract—The hypothesis that intracranial energy deposition from handheld cellular telephones causes acoustic neuroma was tested in an epidemiologic study of 90 patients and 86 control subjects. The relative risk was 0.9 (p = 0.07) and did not vary significantly by the frequency, duration, and lifetime hours of use. In patients who used cellular telephones, the tumor occurred more often on the contralateral than ipsilateral side of the head. Further efforts should focus on potentially longer induction periods.

Impact of dairy products and dietary calcium on bone-mineral content in children: Results of a meta-analysis

OBJECTIVE Although calcium is essential for maintaining bone health in children, the optimum dietary intake of calcium in this age group, particularly in the form of dairy foods, is not well defined. A meta-analysis was conducted to examine the impact of dietary calcium/dairy supplementation on bone mineral content in this age group. METHODS Data were pooled from randomized controlled intervention trials and observational studies using previously described methods. The outcome of interest was a summary mean difference bone mineral content. Sensitivity analyses were employed to evaluate any observed statistical heterogeneity and to examine the influence of specific study characteristics on the summary estimate of effect. RESULTS Initially combining data from twenty-one randomized controlled trials (RCTs) using total body bone mineral content (TB-BMC) as the outcome of interest, yielded a non-statistically significant increase in TB-BMC of 2 g (supplemented versus controls). These data demonstrated substantial statistical heterogeneity with sensitivity analyses revealing that among study subjects with normal or near normal baseline dietary calcium/dairy intakes, supplemental dairy/calcium showed little impact on bone mineral content. Sensitivity analyses suggested that baseline calcium intake could potentially account for the statistical heterogeneity. Pooling the three reports utilizing low intake subjects yielded a statistically significant summary mean BMC of 49 g (24.0-76-6). Pooling two RCTs using calcium/dairy supplement plus vitamin D was also associated with an increase in lumbar spine BMC of, on average, 35 g (-6.8-41.8). The lack of data using BMC measurements at other anatomic sites as well as sparse data from non-randomized studies, precluded further statistical pooling. CONCLUSION Increased dietary calcium/dairy products, with and without vitamin D, significantly increases total body and lumbar spine BMC in children with low base-line intakes.

Dairy Products, Dietary Calcium and Vitamin D Intake as Risk Factors for Prostate Cancer: A Meta-Analysis of 26,769 Cases From 45 Observational Studies

In this study, we examined the available evidence and sources of heterogeneity for studies of dairy products, calcium, and vitamin D intake and the risk of prostate cancer. We pooled data from 45 observational studies using a general variance-based, meta-analytic method employing CIs. Summary relative risks (RRs) were calculated for specific dairy products such as milk and dairy micronutrients. Sensitivity analyses were performed to test the robustness of these summary measures of effect. Cohort studies showed no evidence of an association between dairy [RR = 1.06; 95% confidence interval (CI) = 0.92–1.22] or milk intake (RR = 1.06; 95% CI = 0.91–1.23) and risk of prostate cancer. This was supported by pooled results of case-control analyses (RR = 1.14; 95% CI = 1.00–1.29), although studies using milk as the exposure of interest were heterogeneous and could not be combined. Calcium data from cohort studies were heterogeneous. Case-control analyses using calcium as the exposure of interest demonstrated no association with increased risk of prostate cancer (RR = 1.04; 95% CI = 0.90–1.15). Dietary intake of vitamin D also was not related to prostate cancer risk (RR = 1.16; 95% CI = 0.98–1.38). The data from observational studies do not support an association between dairy product use and an increased risk of prostate cancer.

Family history of cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology consortium

Alcohol and tobacco consumption are well‐recognized risk factors for head and neck cancer (HNC). Evidence suggests that genetic predisposition may also play a role. Only a few epidemiologic studies, however, have considered the relation between HNC risk and family history of HNC and other cancers. We pooled individual‐level data across 12 case–control studies including 8,967 HNC cases and 13,627 controls. We obtained pooled odds ratios (OR) using fixed and random effect models and adjusting for potential confounding factors. All statistical tests were two‐sided. A family history of HNC in first‐degree relatives increased the risk of HNC (OR = 1.7, 95% confidence interval, CI, 1.2–2.3). The risk was higher when the affected relative was a sibling (OR = 2.2, 95% CI 1.6–3.1) rather than a parent (OR = 1.5, 95% CI 1.1–1.8) and for more distal HNC anatomic sites (hypopharynx and larynx). The risk was also higher, or limited to, in subjects exposed to tobacco. The OR rose to 7.2 (95% CI 5.5–9.5) among subjects with family history, who were alcohol and tobacco users. A weak but significant association (OR = 1.1, 95% CI 1.0–1.2) emerged for family history of other tobacco‐related neoplasms, particularly with laryngeal cancer (OR = 1.3, 95% CI 1.1–1.5). No association was observed for family history of nontobacco‐related neoplasms and the risk of HNC (OR = 1.0, 95% CI 0.9–1.1). Familial factors play a role in the etiology of HNC. In both subjects with and without family history of HNC, avoidance of tobacco and alcohol exposure may be the best way to avoid HNC.

Cigarette smoking and plasma cholesterol

Plasma cholesterol levels were determined for 51,723 participants of community-based cholesterol screenings in 10 United States cities during 1988. Among white adult men and women under the age of 60 without other cardiovascular disease risk factors, a dose-response relationship was found between the number of cigarettes smoked per day and increasing levels of plasma cholesterol. In men aged 18 to 60 years, average plasma cholesterol increased by 0.33 mg/dl for each cigarette smoked (p less than 0.001); in women aged 31 to 50 years, average plasma cholesterol increased by 0.48 mg/dl for each cigarette smoked (p less than 0.001). Plasma cholesterol levels among ex-smokers were found to be similar to those of nonsmokers. No association between cigarette smoking and levels of plasma cholesterol was observed in men and women over age 60. Possible mechanisms for this observed relationship include an antiestrogenic effect of cigarette smoking that makes the observation more noticeable in younger female cohorts, enhanced lipolysis that increases levels of plasma free fatty acids, or differences in dietary intake between smokers and nonsmokers.