Null effect of circulating sphingomyelins on risk for breast cancer: A Mendelian randomization report using Breast Cancer Association Consortium (BCAC) data


Background: Changes in cellular metabolism are a hallmark of cancer and are linked with sphingolipid synthesis. Due to immense interest in how sphingolipids influence chemoresistance, more is known about the impact of sphingolipids during cancer treatment and progression than about the potential role of sphingolipids in the induction of tumors in humans.
Methods: Because estrogen triggers sphingolipid signaling cascades, the causal role of circulating levels of sphingomyelin (a type of sphingolipid) on breast cancer was investigated with a well-powered Mendelian randomization design.
Results: The results reveal a null effect (OR = 0.94; 95% CI = 0.85, 1.05; P = 0.30).
Conclusion: Despite the role sphingomyelins play during chemoresistance and cancer progression, circulating sphingomyelins do not appear to initiate or protect from breast cancer. This finding comprises the first causal report in humans that sphingomyelins on breast cancer initiation is null. Future investigations of risk in other cancer types are needed to further explore the potential role of sphingolipid biology in cancer etiology.

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