Two recent, independently conducted studies converge on a deceptively simple but biologically powerful idea: the more cells at risk, the higher the chance of cancer.

This insight, although intuitive, opens a Pandora’s box of deeper biological, epidemiological, and therapeutic questions. It also rekindles the Tomasetti–Vogelstein hypothesis, which proposes that variation in cancer incidence across tissues is largely explained by the number of stem cell divisions.

Parallel Findings from Divergent Angles

Study 1: Faraz et al. (2025) A global analysis linked larger breast cup size to increased breast cancer incidence. The underlying hypothesis? Larger breast volume contains more epithelial cells, the primary origin of breast carcinomas. More target cells mean more chances for replication errors and mutagenic events.

Study 2: Panahi Meymandi & Ghaderi (2025) This mechanistic review explored how adipose-derived stem cells (ADSCs) in obese individuals may fuel tumor development. Beyond their sheer abundance in adipose tissue, ADSCs facilitate malignancy by enhancing angiogenesis, immune evasion, and even resistance to therapy. Again, quantity correlates with vulnerability.

Both studies reinforce the idea that cellularity—specifically, the number of active or stem-like cells—may be a hidden denominator in cancer risk.

The Provocative Question: Are We Underestimating the Role of "Numbers" in Oncogenesis?

These findings challenge us to ask:

• Are cell counts (not just mutations, hormones, or environment) the underappreciated variable in cancer epidemiology?
• Could this help explain gender-specific differences in cancers beyond breast tissue (e.g., endometrial, prostate)?
• Should anatomical volume or organ cell burden be incorporated into existing risk models?
• Are we placing too much emphasis on molecular targets, while overlooking basic cellular ecology?

Let's Push the Boundaries

We invite oncologists, cell biologists, radiologists, epidemiologists, and stem cell researchers to share their insights:

• Could organ volume and stem cell density serve as predictive biomarkers?
• How can we quantify at-risk cell populations in vivo across different organs?
• Could interventions that reduce proliferative cell pools (e.g., lifestyle, drugs) have a preventive effect?
• Where does this hypothesis fit among genetic, environmental, and stochastic models of cancer?

This is more than a correlation—it’s a potentially unifying framework for understanding cancer risk. If you’re working on related models or have critiques of the Tomasetti–Vogelstein paradigm, we want to hear from you.

Do numbers truly matter more than we think? Please share your thoughts, evidence, or challenges below.

References

Faraz M, Nematollahi S, Tahmasebi S, Welsh JS, Bevelacqua JJ, Mortazavi SMJ, Mortazavi SA. The Association between Breast Cup Size and Breast Cancer Incidence: Insights from a Global Dataset. J Biomed Phys Eng. 2025 Feb 1;15(1):93-100. doi: 10.31661/jbpe.v0i0.2412-1869. PMID: 39975528; PMCID: PMC11833153.

Panahi Meymandi AR, Ghaderi A. Adipose-Derived Stem Cells at the Crossroads of Obesity and Cancer. Stem Cell Rev Rep.. 2025 Jul 3. doi: 10.1007/s12015-025-10918-4. Epub ahead of print. PMID: 40608181.