History of cancer was not ascertained by REGARDS. Our study indicates the presence of chronic medical conditions but not their quality of control. We could not detect potentially relevant comorbidities such as chronic liver disease. Because of the focus of this analysis on chronic medical conditions, we opted to limit examination of these and other confounders. The major form of genomic instability is chromosomal instability, which is characterized by continuous generation of new structural and numerical chromosome aberrations. Amongst various forms of chromosome aberrations, pericentromeric or centromeric translocations, deletions and iso-chromosomes have been frequently observed in human cancers of various origins such as head and neck, breast, lung, bladder, liver, colon, ovary, pancreas, prostate, and uterine cervix. This highlights an important general role of pericentromeric instability in cancer development. Centromeric or pericentromeric instability may contribute to cancer development by at least two routes. Firstly, chromosome aberrations occurring at pericentromeric regions FDA-approved Compound Library inhibitor usually result in whole-arm chromosome imbalances, leading to large scale alterations in gene dosage. Secondly, the heterochromatin in centromeric or pericentromeric regions encompasses multiple forms of chromatin structure that can lead to gene silencing or deregulation. Pericentromeric or centromeric instability has been proposed to be one of the basic forms of chromosome instability. So far, the mechanisms of pericentromeric instability in cancer development are poorly understood. Cancer development is associated with replication stress. Replication stress is defined as either inefficient DNA replication, or hyper-DNA replication caused by the activation of origins at rates of more than once per S phase due to the expression of oncogenes or, more generally, the activation of growth signaling pathways. Replication stress is known to cause genomic instability particularly at chromosome loci that are intrinsically difficult to replicate because of the complexity of secondary structures or difficulty in unwinding during DNA replication. The term “chromosomal fragile sites” is designated to describe the recurrent loci that preferentially exhibit chromatid gaps and breaks on metaphase chromosomes under partial inhibition of DNA synthesis. The list of such loci is growing and now includes classical “chromosomal fragile sites”, telomeres, and repetitive sequences. Human centromeres consist largely of repetitive short sequences that are tightly packed into centromeric heterochromatin. The condensed structure of heterochromatin has been envisaged to present barriers to DNA replication. The problematic progression of replication fork in centromeric or pericentromeric regions may generate DNA lesions under replication stress. If these lesions are not promptly repaired, they can lead to centromeric or pericentromeric chromosome aberrations. High-risk human papillomaviruses such as HPV16 and HPV18 are strongly associated with uterine cervical cancer, a leading cause of cancer-related deaths in women worldwide. Infection with high-risk types of HPV may also play a role in other human cancers including esophageal cancer. The viral oncogenes E6 and E7 encoded by high-risk HPV inactivate p53 and Rb proteins, respectively, by accelerating proteolytic degradation of the proteins. Both p53 and Rb are master tumor suppressors in human cells. In epithelial cells, high-risk HPV E6 can also activate telomerase, which facilitates cellular immortalization, one of the hallmarks of cancer. But in some cell lines, the telomerase activation by HPV E6 may not be efficient enough.