Cancer risk is often elevated by an array of environmental and lifestyle factors. But there is more at play here. In an interview with HT Lifestyle, Dr Sewanti Limaye, director, medical and precision oncology at Sir H.N. Reliance Hospital, Mumbai said, “There are a number of recognised common risks such as smoking and tobacco products, and poor dietary choices, but there are also some less well-known silent risk factors that may push a person into malignancy over a long period of time with no obvious disease warning signs.”
Here are a few silent factors that can raise the risk of cancer:
1. Chronic low-grade inflammation
Chronic low-grade inflammation promotes multidimensional cancer through the release of proinflammatory cytokines such as IL-6, TNF-α, and CRP, and is connected to the signaling of NF-kB and STAT3 pathways. The activation of these pathways drives angiogenesis, genomic instability, and epithelial–mesenchymal transition. Although the patient may not be aware of it, having obesity and associated conditions like metabolic syndrome, having periodontal disease, and persistent chronic infections can contribute to a pro-tumor microenvironment that will eventually lead to malignant transformation of the epithelium with no precursors.
2. Endocrine-Disrupting Chemicals (EDCs)
EDCs are found in a large range of consumer products, from plastics (bisphenol A, phthalates, etc), to pesticides, to cosmetics. EDCs can either mimic or block natural hormones, leading to the alteration of cell death and cell proliferation rates. They influence the responses of a range of signaling pathways, including ERα, androgen receptor, and AhR. As a whole, they have been linked to a range of significant cancers, particularly breast, prostate, and endometrial cancers. The insidious part of EDCs is that should a person be exposed to the chemical during the prenatal or early-life period, the exposure leads to long-term changes in development and physiology that may not confer cancer risk until decades later.
3. Circadian disruption
Shift work, sleep deprivation, and chronic light exposure interfere with circadian genes (CLOCK, BMAL1, PER, CRY) affecting DNA repair and the regulation of the cell-cycle Its connection to DNA repair reduces melatonin which has its own antioxidative properties that also make us more vulnerable. The IARC classifies night-shift work as a Group 2A carcinogen, suggesting night-shift workers have double the risk of developing breast and colorectal cancers relative to daytime workers after long-term exposure.
4. Dysbiosis of gut microbiome
An imbalance of gut flora, defined by the loss of microbial diversity and expansion by taxa such as Fusobacterium nucleatum, generates genotoxins like colibactin, maintains mucosal inflammation, and alters bile acid metabolism, leading to an environment that promotes colorectal carcinogenesis and possibly hepatobiliary and pancreatic cancers, often without noticeable early signs.
5. Air pollution and PM2.5
Fine particulate matter (PM2.5) is a Group 1 carcinogen that penetrates the lungs deep into alveoli, generating oxidative stress, DNA adducts and incorrect methylation. Long-term cohort studies have demonstrated an increase in lung cancer incidence and associated PM2.5 exposure, even in nonsmokers. Its carcinogenic potential can be particularly nefarious because a majority of the time clinical detection occurs late.
6. Oncogenic viral infections
Virus like HPV, HBV, HCV, EBV integrate into cellular DNA. They also produce proteins (HPV E6/E7, HBV X, EBV LMP1) that also inactivate tumor suppressor proteins (p53 and Rb), change epigenetics, and allow for immune evasion. Chronic infection may be asymptomatic for many years before the development of cervical cancer, liver cancer, or nasopharyngeal cancer.
