Abstract
MACC1 (Metastasis Associated in Colon Cancer 1) is found to regulate the hepatocyte growth factor (HGF)/Met signal pathway, and plays an important role in tumor proliferation, angiogenesis, and metastasis. However, the relationships between MACC1 SNPs (single nucleotide polymorphisms) and oral cancer are still blurred. In this study, five SNPs (rs3095007, rs1990172, rs4721888, rs975263, and rs3735615) were genotyped in 911 oral cancer patients and 1200 healthy individuals by real-time polymerase chain reaction (PCR), and the associations of oral cancer with the SNP genotypes, environmental risk factors, and clinicopathological characteristics were further analyzed. Our results showed that individuals who had GC genotype or C-allele (GC + CC) in rs4721888 would have a higher risk for oral cancer incidence than GG genotype after adjustment for betel quid chewing, cigarette smoking, and alcohol drinking. Moreover, the 715 oral cancer patients with a betel quid chewing habit, who had C-allele (TC + CC) in rs975263, would have a higher risk for lymph node metastasis. Further analyses of the sequences of rs4721888 revealed that the C-allele of rs4721888 would be a putative exonic splicing enhancer. In conclusion, MACC1 SNP rs4721888 would elevate the susceptibility for oral cancer, and SNP rs975263 would increase the metastasis risk for oral cancer patients with a betel quid chewing habit. Our data suggest that SNP rs4721888 could be a putative genetic marker for oral cancer, and SNP rs975362 may have the potential to be a prognostic marker of metastasis in an oral cancer patient.
Highlights
According to the global cancer statistics 2018, of the 18.1 million global new cases of all cancers, oral cancer is around 2.0% and its death is around 1.9% of the 9.6 million cancer deaths [1]
In the aspect of carcinogenic substances and living habits, 78.5% of people were used to betel quid chewing in the patient group, but only 16.6% in the control group (p < 0.001); 88.8% of people were used to cigarette smoking in the patient group, and 53% in the control group (p < 0.001); 53.8% of people were used to alcohol drinking in the patient group, and 19.7% in the control group (p < 0.001)
Betel quid chewing, alcohol drinking, and cigarette smoking habits were significantly associated with oral squamous cell carcinoma (OSCC) (Table 1)
Summary
According to the global cancer statistics 2018, of the 18.1 million global new cases of all cancers, oral cancer is around 2.0% and its death is around 1.9% of the 9.6 million cancer deaths [1]. In Taiwan, the incidence of oral cancer was 21.98 per 100,000 persons in 2017. One of the head and neck cancers (HNCs), are highly aggressive malignancies with a high mortality rate, and the five-year survival rate of the distant stage is lower than 50%. OSCC is one of the most common tumors of the head and neck region, and it is an undifferentiated nonkeratinizing carcinoma in the histological aspect with a high potential for metastasis. The factors associated with OSCC are human papillomavirus infection [3,4,5,6], and ordinary cultural habits such as smoking, drinking alcohol, and betel quid chewing, which is a popular risk for oral tumorigenesis in south-east Asian countries [7]
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