Increasing incidence of anogenital warts with an urban–rural divide among males in Manitoba, Canada, 1990–2011

Abstract Background Anogenital warts (AGW) are caused by the most common sexually transmitted infection, human papillomavirus. The objective of this study was to examine AGW incidence from 1990 to 2011 by sex, age, income quintile, and residential area category (urban/rural). The study period included the initiation of school-based HPV vaccination for girls in the sixth grade, which began in 2008. The data presented in this paper may also be useful for establishing baseline rates of AGW incidence which may be used to evaluate the success of the school-based HPV immunization program. Methods Cases of anogenital warts were identified using Manitoba’s administrative databases of Physician Claims and Hospital Discharge Abstracts. Annual age-standardized incidence in Manitoba from 1990 to 2011 was calculated. Incident AGW rates were compared by sex, age group, residential area category (urban/rural), and household income quintile using logistic regression. Joinpoint regression analyses were used to evaluate the time trends of AGW. Results Prior to 2000, AGW incidence was higher among females than males. However, from 2000 to 2011 the incidence was higher among males and increased steadily over time. AGW incidence tended to peak in younger age groups among females compared to males. Females and males living in urban areas had nearly twice the odds of AGW occurrence compared to those in rural areas. Conclusions There is a need for education about AGW in male population. The upcoming initiation of HPV vaccination among boys may reduce the incidence and should be evaluated

Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes

Metabolic reprogramming such as the aerobic glycolysis or Warburg effect is well recognized as a common feature of tumorigenesis. However, molecular mechanisms underlying metabolic alterations for tumor therapeutic resistance are poorly understood. Through gene expression profiling analysis we found that histone H3K36 methyltransferase NSD2/MMSET/WHSC1 expression was highly elevated in tamoxifen-resistant breast cancer cell lines and clinical tumors. IHC analysis indicated that NSD2 protein overexpression was associated with the disease recurrence and poor survival. Ectopic expression of NSD2 wild type, but not the methylase-defective mutant, drove endocrine resistance in multiple cell models and xenograft tumors. Mechanistically, NSD2 was recruited to and methylated H3K36me2 at the promoters of key glucose metabolic enzyme genes. Its overexpression coordinately up-regulated hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD), two key enzymes of glycolysis and the pentose phosphate pathway (PPP), as well as TP53-induced glycolysis regulatory phosphatase TIGAR. Consequently, NSD2-driven tamoxifen-resistant cells and tumors displayed heightened PPP activity, elevated NADPH production, and reduced ROS level, without significantly altered glycolysis. These results illustrate a coordinated, epigenetic activation of key glucose metabolic enzymes in therapeutic resistance and nominate methyltransferase NSD2 as a potential therapeutic target for endocrine resistant breast cancer