Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

A 62-year-old female visited our clinic with progressively decreased vision in both eyes beginning 12 years prior. Idiopathic corneal opacity in all layers of the cornea was found in both eyes. One year later, we performed penetrating keratoplasty on the undiagnosed right eye. During post-surgical follow-up, corneal edema and stromal opacity recurred, and penetrating keratoplasty was performed two more times. The patient's total serum protein level, which had previously been normal, was elevated prior to the final surgery. She was diagnosed with monoclonal gammopathy of undetermined significance. We made a final diagnosis of monoclonal gammopathy-associated crystalline keratopathy after corneal biopsy. Monoclonal gammopathy-associated crystalline keratopathy is difficult to diagnose and may lead to severe visual loss. A systemic work-up, including serologic tests like serum protein or cholesterol levels, is needed in patients with unexplainable corneal opacity.
Corneal Edema/etiology/*metabolism/physiopathology/surgery ; Corneal Neovascularization/etiology/*metabolism/physiopathology/surgery ; Corneal Opacity/etiology/*metabolism/physiopathology/surgery ; Crystallins/*metabolism ; Female ; Humans ; Keratoplasty, Penetrating ; Microscopy, Electron ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance/*complications/pathology ; Reoperation ; Visual Acuity