ORIGINAL ARTICLE Is cholesterol a mediator of cold-induced cancer? Chandi C. Mandal 1 & Ankit Sharma 1 & Mahaveer S. Panwar 2 & James A. Radosevich 3 Received: 2 August 2015 /Accepted: 6 January 2016 # International Society of Oncology and BioMarkers (ISOBM) 2016 Abstract Many factors such as smoking, obesity, and high fat have been either directly or indirectly linked to cancer deaths and/or incidences. Similarly, abnormal serum cholesterol levels have been assigned as a risk factor for cancer, but some studies show a discrepant result. To resolve this discrepancy, we have analyzed cholesterol data of 166 countries. Univari- ate analysis showed a positive correlation between serum av- erage total cholesterol (ATC) and overall cancer mortality rate (CMR) [tau = 0.277, z = 5.19, p < 0.0001]. It was also observed that a similar positive correlation was found between ATC and different anatomical site-specific CMRs in lung, bladder, ovarian, breast, and pancreatic cancers. Our recent published data documented an existence of a negative correlation be- tween average annual temperature (AAT) and overall CMR, as well as CMR of the abovementioned anatomical site- specific cancers. Statistical analysis further shows a negative correlation between AAT and ATC, similar to that of AAT and CMR. The resulting patterns of univariate analysis between AAT and CMR are almost identical with AAT and ATC, when this analysis was performed every 2 °C of AAT increment for all countries. Moreover, geographical location of the top 50 countries having the highest CMR is almost similar to the top 50 countries having the highest ATC. Similarly, the least 50 countries having the lowest CMR are located in the same geographical region, similar to the least 50 countries having the lowest ATC. These data along with other literature reports suggest that cholesterol could be a mediator of cold-induced cancer mortality. Keywords Environmental temperature . Cancer mortality rate . Cholesterol . Geographical location . Cancer-causing factors Introduction Cancers are one of leading causes of morbidity and mortality worldwide. The World Health Organization (WHO) has re- ported 14 million new cases and 8.2 million cancer- associated deaths worldwide in 2012. The treatment of cancer arising in a particular tissue with a specific drug does not always result in an identical response, because cancer is a complex group of diseases. The pathophysiology and molec- ular biology not only markedly differ in cancer types but also from one patient to other patient. The heterogenetic nature of cancer and cancer-associated fibroblast, stromal, immune, and macrophage cells that are present in tumor tissue vary from one tumor to other [1–6]. Acquired genetic mutations may lead to develop genetic in- stability which may drive tumor growth [7]. In addition, the epigenetic changes have also been linked with tumor initia- tion, cancer progression, and metastasis [8–10]. A recent study suggested that both epigenetic changes and genetic mu- tation can cooperate to initiate tumorigenesis and progression [11]. Moreover, the tumor progression is simultaneous with Electronic supplementary material The online version of this article (doi:10.1007/s13277-016-4799-2) contains supplementary material, which is available to authorized users. * Chandi C. Mandal chandicmandal@gmail.com 1 Department of Biochemistry, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, 305817 Ajmer, Rajasthan, India 2 Department of Statistics, Central University of Rajasthan, 305817 Ajmer, Rajasthan, India 3 Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA Tumor Biol. DOI 10.1007/s13277-016-4799-2