Breast cancer, alcohol, and phosphate toxicity

Abstract

Alcohol consumption is associated with an increased risk of breast cancer, even at low alcohol intake levels, but public awareness of the breast cancer risk associated with alcohol intake is low. Furthermore, the causative mechanisms underlying alcohol's association with breast cancer are unknown. The present theoretical paper uses a modified grounded theory method to review the research literature and propose that alcohol's association with breast cancer is mediated by phosphate toxicity, the accumulation of excess inorganic phosphate in body tissue. Serum levels of inorganic phosphate are regulated through a network of hormones released from the bone, kidneys, parathyroid glands, and intestines. Alcohol burdens renal function, which may disturb the regulation of inorganic phosphate, impair phosphate excretion, and increase phosphate toxicity. In addition to causing cellular dehydration, alcohol is an etiologic factor in nontraumatic rhabdomyolysis, which ruptures cell membranes and releases inorganic phosphate into the serum, leading to hyperphosphatemia. Phosphate toxicity is also associated with tumorigenesis, as high levels of inorganic phosphate within the tumor microenvironment activate cell signaling pathways and promote cancer cell growth. Furthermore, phosphate toxicity potentially links cancer and kidney disease in onco‐nephrology. Insights into the mediating role of phosphate toxicity may lead to future research and interventions that raise public health awareness of breast cancer risk and alcohol consumption.

Can a Low-Phosphate Diet for Chronic Kidney Disease Treat Cancer? An Interdisciplinary Literature Review

“…In 2023, the present authors published a review proposing that the association of alcohol consumption with increased risk of breast cancer is mediated by hyperphosphatemia caused by alcohol-induced rhabdomyolysis which releases intracellular phosphate from skeletal muscle into the serum [35]. Also in 2023, the authors found that a 2.30 relative risk for breast cancer incidence in a cohort of middle-aged U.S. women was associated with >1800 mg dietary phosphorus compared to 800-1000 mg phosphorous recommended by the U.S. National Kidney Foundation for patients with CKD (RR: 2.30; 95% CI: 0.94-5.61; p = 0.07) [36].…”

“…"Limit alcohol consumption-For cancer prevention, it's best not to drink alcohol" Non-traumatic rhabdomyolysis from alcohol intake increases serum Pi [35].…”

“…"For mothers: breastfeed your baby, if you can-Breastfeeding is good for both mother and baby" Breast milk is six-times lower in phosphorus compared to cow's milk [66], and increased need for phosphate during pregnancy and lactation may mitigate effects of excessive dietary phosphate intake [35].…”

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate

“… High dietary phosphate and cancer-cell signaling [ 96 ]. This flowchart shows that high dietary phosphate activates the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway while deactivating tumor suppression by PTEN and CTMP, increasing cell growth in tumorigenesis.…”

Unraveling breast cancer prognosis: a novel model based on coagulation-related genes

“…Breast cancer exhibits diversity at the biological level, with prognosis being impacted by a range of factors such as molecular subtypes, age at diagnosis, and histopathological features ( Brown et al, 2023 ). Recent advancements in early detection methods for breast cancer and the ongoing progress in treatment options have greatly enhanced the outlook for patients with this disease ( Will et al, 2023 ; Brown et al, 2024 ). Especially as people’s understanding of the immune microenvironment deepens, the utility of immunotherapy in breast cancer treatment continues to ascend.…”