Alcohol-metabolizing Enzymes' Gene Polymorphisms and Susceptibility to Multiple Head and Neck Cancers

Abstract

Multiple primary tumors (MPT), especially in the hypopharynx and esophagus, are challenging in patients with head and neck cancer (HNC). Alcohol and alcohol-metabolizing genes were reported to be related to upper digestive tract cancers. Here, we investigated whether the genotypes of alcoholmetabolizing enzymes (ADH1B, ADH1C, and ALDH2) affected patients' susceptibility to developing MPTs. We recruited 659 male patients with HNC between March 1996 and February 2017. Age-and gender-matched controls were also recruited. A total of 164 patients with HNC were identified to have second or third malignancies. The single-nucleotide polymorphisms in ADH1B (rs1229984), ADH1C (rs698), and ALDH2 (rs671) were analyzed by Taq-Man assays. The prevalence of ALDH2 à 2 allele carriers is significantly higher than that of à 1 à 1 homo-zygotes for oral cavity (P ¼ 0.013) and oropharyngeal cancers (P ¼ 0.012). For ADH1B, the number of à 1 allele carriers is significantly higher than that of à 2 à 2 homozygotes for oropharyngeal (P ¼ 0.017) and hypopharyngeal cancers (P < 0.001). ADH1C (rs698) SNPs are not significantly associated with tumor subsites (all P > 0.05). Polymorphisms in ALDH2 (à 2 allele carriers) and ADH1B (à 1 allele carriers) significantly increase the risk of developing MPTs in the upper digestive tract [P < 0.001, OR (95% confidence interval (CI): 5.186 (2.444-11.004) and P < 0.05, OR (95% CI): 2.093 (1.149-3.812), respectively]. ALDH2 (rs671) à 2 and ADH1B (rs1229984) à 1 allele carriers were shown to develop MPTs in the upper digestive tract. Genetic information may be used to identify high-risk patients for the development of MPTs.

Association Between the Aldehyde Dehydrogenase‐2 rs671 G>A Polymorphism and Head and Neck Cancer Susceptibility: A Meta‐Analysis in East Asians

“…After the screening of titles, abstracts, and full texts, 496 articles were excluded. In total, 13 articles (14 case–control studies) comprising of 4,312 HNC patients and 6,627 controls were included in this meta‐analysis (Asakage et al, 2007; Chien et al, 2019; Hashimoto et al, 2006; Hiraki et al, 2007; Huang et al, 2017; Ji et al, 2011; Katoh et al, 1999; Koyanagi et al, 2017; Nomura et al, 2000; Yamashita et al, 2019; Yokoyama et al, 1998; Yuan et al, 2013; Zhang et al, 2014). All the included studies focused on East Asian populations.…”

“…In 2 studies, the genotype frequencies in the control group deviated from HWE (Yuan et al, 2013; Zhang et al, 2014). With respect to genotyping, 6 studies used the polymerase chain reaction–restriction fragment length polymorphism method (Asakage et al, 2007; Katoh et al, 1999; Nomura et al, 2000; Yamashita et al, 2019; Yokoyama et al, 1998; Zhang et al, 2014), and 8 used the TaqMan method (Chien et al, 2019; Hashimoto et al, 2006; Hiraki et al, 2007; Huang et al, 2017; Ji et al, 2011; Koyanagi et al, 2017; Yuan et al, 2013). All the included information is shown in Table 2.…”

“…Individuals with abnormal expression or structural abnormalities of ALDH2 exhibit substantially reduced ACH oxidation, resulting in the accumulation of ACH. As a result, these individuals have an increased risk of cancers such as esophageal cancer (Matejcic et al, 2017), gastric cancer (Matsuo et al, 2013), hepatocellular cancer (Seo et al, 2019), and other upper digestive tract cancer (Chien et al, 2019; Shin et al, 2011). Today, several studies have shown that alcohol intake is closely related to the incidence of HNC, and increased alcohol intake is associated with a poorer overall survival rate (Bagnardi et al, 2015; Sawabe et al, 2017; Shanmugham et al, 2010).…”

Familial Aggregation of Head and Neck Cancer in Taiwan

“…One example is the study by Chien et al, in which they found that carriers of the ALDH2*2 and ADH1B*1 alcohol metabolism gene polymorphisms had higher risks of multiple primary cancers in the upper digestive tract in a Taiwanese population. 40,41 In patients with lung cancer, it has been shown that the glutathione S-transferase M1 null genotype is significantly associated for patients who had less than 40 pack years of tobacco exposure. 6 Familial aggregation of HNC was observed in this large database analysis, which was not easily investigated in usual cohorts.…”

Polygenic Panels Predicting the Susceptibility of Multiple Upper Aerodigestive Tract Cancer in Oral Cancer Patients

“…Previously, we identified that alcohol metabolizing enzymes play roles in the tumor formation in upper aerodigestive tract (ADT) cancers in head and neck cancer patients [ 16 ]. In this study, we intended to search novel genetic polymorphism loci predicting the susceptibility of MPTs in OSCC patients on a genome-wide scale.…”