New Delhi: The pathogenesis of cancer is multifactorial, due to a complex interplay among genetic predisposition, environmental exposures, and lifestyle factors. The lay community can easily identify carcinogenic activity causes such as tobacco use, diet, and smoking, but there are several “silent” or less identified contributory carcinogenic activities with decades of accumulating risk. I will detail six such contributors, including biological rationale and clinical recognition.
In an interview with News9Live, Dr Sewanti Limaye, Director – Medical & Precision Oncology at Sir H.N. Reliance Hospital, Mumbai, listed the silent risk factors of cancer.
Chronic Low-Grade Inflammation
Chronic low-grade inflammation itself is a known cancer promoter. Inflammatory cytokines (e.g., IL-6, TNF-α, and CRP may mainly induce the inflammatory pathways in other tissues (e.g., NF-kB, STAT3) to lead to angiogenesis, genomic instability, and epithelial-mesenchymal transition. Chronic obesity, metabolic syndrome, chronic periodontal disease, or chronic infections create a pro-tumour microenvironment, but the latency can be null experience for the patient as their symptoms seldom persist on till malignant transformation has taken place.
Endocrine-disrupting Chemicals (EDCs)
Due to their ubiquitous presence in plastics (such as bisphenol A and phthalates), pesticides, and cosmetics, EDCs can mimic or block hormonal messages. These chemicals control cell growth and death by ERα mechanisms of the estrogen receptor, the androgen receptor, and the aryl hydrocarbon receptor (AhR). Even epidemiological research indicates some positive relationships between endocrine-disrupting chemicals (s) (EDCs) and breast, prostate, and endometrial cancers. Their heinous nature is that they possess the ability to produce disastrous outcomes (e.g., cancer) by inducing exposures in early life or in utero that are not phenotypically manifested for decades!
Dispersion of Circadian Harmony
Night shifts, sleep deprivation pattern, and prolonged light exposure can all combine to vitiate the molecular circadian clock (CLOCK, BMAL1, PER, CRY genes), thereby causing derangement of cell-cycle checkpoints and reducing the fidelity of DNA repair. The melatonin activity further declines (this has antioxidative protective effects).
In relation to night shift work as being possibly carcinogenic, the International Agency for Research on Cancer (IARC) has designated night work as a Group 2A carcinogen with high risk observed, specifically for breast and colorectal cancers. For example, premenopausal women working ≥3 night shifts/week for >20 years have more than double the risk of breast cancer than day workers. Further mechanistic studies using Per2-deficient mice showed increased tumor induction after radiation exposure and enhanced colon polyp formation, ascertaining that dysregulation of the molecular clock plays a role in tumorigenesis.
Gut Microbiome Dysbiosis
The gut microbiota possesses significant immunomodulatory and metabolic impacts. Dysbiosis, or loss of microbial diversity and an increase in pathogenic populations (e.g., Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis) that produce genotoxins, e.g., colibactin, cause chronic mucosal inflammation, and alter bile acid metabolism, is accountable for colorectal carcinogenesis and also may be presumed to play a role in hepatobiliary and pancreatic cancer. The dangerous aspect is that the patient will not always have symptoms of microbial imbalance until after neoplasia.
Particulate Matter (PM2.5) and Air Pollution
Fine particulate matter (PM2.5) air pollution is now solidly classified as a Group 1 carcinogen by IARC. Following inhalation in adequate doses, particulate matter is able to enter the alveoli and cause oxidative stress, DNA adducts, and methylation alterations.
Cohort studies follow up people over years and establish that long-term exposure to PM2.5 is associated with a higher incidence of lung cancer, regardless of whether a person is a smoker or not. The lack of acute clinical presentation and delayed diagnosis suggests its “silent” carcinogenicity. For example, chronic exposure to fine particulate matter (PM2.5) is a Group 1 carcinogen by IARC classification and a separate risk factor for lung cancer—also in nonsmokers—via oxidative DNA damage and alveolar epithelium mutagenesis.
Viral Latency and Oncogenic Infections
Oncogenic viruses such as Human Papillomavirus (HPV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Epstein-Barr Virus (EBV) are often secretly incorporated into host cells. Viral oncoproteins (HPV E6/E7, HBV X protein, EBV LMP1) disrupt tumor suppressor pathways (p53, Rb), enable epigenetic modification, and alter immune evasion. Chronic carriers remain asymptomatic for years before the onset of cervical, hepatocellular, or nasopharyngeal carcinomas, respectively.
Summary
Cancer risk is not determined by overt lifestyle habits but by low-dose, latent, and often insensible exposures that persist for decades. As oncologists, we need to find these subtle determinants of cancer risk in young years, describe their significance, and integrate them into multi-level strategies for prevention—redirecting the business from terminal disease management to prevention of cancer.