Beyond Tobacco: High sugar intake as a potential risk factor for oral cavity cancers amongst non-tobacco users?

According to Globocan 2022, more than 1,40,000 new oral cavity cancers cases are diagnosed every year in India. A major etiological factor is rampant use of smokeless tobacco. According to GATS 2016, 42.4% of all adult men and 28.6% of adults consume tobacco in some form. While tobacco accounts for 85% of all the oral cancer cases nearly 15% of the oral cancer are due to other unknown causes suggesting underrecognised etiologies. Percentage of the causes of oral cancer due to unknown causes increases with decrease in usage of tobacco as in western population. As oncologists, we increasingly come across oral cancer patients who deny any tobacco use and often ask “Why did I get cancer despite no tobacco/alcohol abuse?”. Literature is flooded with other potential causes which are not group 1 carcinogen such as chronic mucosal trauma, poor oral hygiene, human papilloma virus (HPV) infection. However, one under recognized factor could be high sugar intake. (HIS) A recent prospective US cohort study conducted by Luis Gomez-Castillo and team studied the association between sugar sweetened beverages (SSB) and the risk of oral cancer in women.[1] The hypothesis stemmed from the earlier Chinese data linking SSB intake with colorectal cancer (RR-1.17). This longitudinal study spanned from 1986- 2017, evaluating 162,602 females. Entire cohort was divided into four groups: SSB serving at least once daily, once in 1 to 7 weeks, once in 1 to 4 months and less than 1 monthly. Multivariate analysis revealed that women consuming 1 or more SSB had 4.87 times higher risk of OCC as compared to those consuming less than once in a month. In fact, oral cancer risk due to SSB use is increased in non-tobacco user (OR-5.46). There are several plausible biological mechanisms to explain high sugar intake (HSI) as potential cause of carcinogenesis. HSI induces high blood glucose leading to insulin surge which in turn leads to higher insulin growth factors (IGFs). These IGFs are known to induce carcinogenesis by causing altered gene expression, angiogenesis and cellular proliferation. HSI is also pro-inflammatory a major hallmark of carcinogenesis. HSI may also disrupt the oral microbiota impairing the immunosurveillance and metabolic response in oral mucosa. Notably, various studies have shown the potential role of metformin (antidiabetic agent) in cancer prevention. Nonetheless, the above study and hypothesis has its limitations. This study only involved women therefore it may not be applicable to men in whom OCC is more prevalent. The number of events (OCC) were less that limits the precision of statistical association. Furthermore, study was predominantly of European descent necessitating further research in more diverse population. This study is relevant to Indian population where OCC is a major health concern and conventionally its linked to rampant tobacco use. However, with rapid urbanization in India, there has been significant shift in higher consumption of high sugar diet. Such study urges clinician and researchers to explore HSI as potential cause of oral cancer particularly among non-tobacco users. This study highlights the potential role of High sugar intake as a significant, underrecognised risk of OCC especially among non-tobacco users. These findings call for further research in the diet related risk of oral cancer especially in non-tobacco chewers. Meanwhile, integrating dietary risk assessment in OCC prevention strategies may be an important step forward in tacking India’s growing burden of oral cancers.