In terms of worldwide levels, Cuba has an intermediate incidence of cancer of the oral cavity and oro-pharynx. We studied 200 cases of cancer of the oral cavity and pharynx, of whom 57 women (median age = 64) and 200 hospital controls, frequency matched with cases by age and sex, in relation to smoking and drinking history, intake of 25 foods or food groups, indicators of oral hygiene and sexual activity, and history of sexually transmitted diseases. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from unconditional multiple logistic regressions and adjusted for age, sex, area of residence, education, and smoking and drinking habits. In the multivariate model, high educational level and white-collar occupation, but not white race, were associated with halving of oral cancer risk. Smoking ≥30 cigarettes per day showed an OR of 20.8 (95% CI: 8.9–48.3), similar to smoking ≥4 cigars daily (OR = 20.5). Drinking ≥ 70 alcoholic drinks per week showed an OR of 5.7 (95% CI: 1.8–18.5). Hard liquors were by far the largest source of alcohol. Increased risk was associated with the highest tertile of intake for maize (OR = 1.9), meat (OR = 2.2) and ham and salami (OR = 2.0), whereas high fruit intake was associated with significantly decreased risk (OR = 0.4). Among indicators of dental care, number of missing teeth and poor general oral condition at oral inspection showed ORs of 2.7 and 2.6, respectively. Number of sexual partners, marriages or contacts with prostitutes, practice of oral sex and history of various sexually transmitted diseases, including genital warts, were not associated with oral cancer risk. 82% of oral cancer cases in Cuba were attributable to tobacco smoking, 19% to smoking cigars or pipe only. The fractions attributable to alcohol drinking (7%) and low fruit intake (11%) were more modest. Thus, decreases in cigarette and cigar smoking are at present the key to oral cancer prevention in Cuba. © 2001 Cancer Research Campaign http://www.bjcancer.com

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10-10) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.