No abstract

Recent analyses in the United States have shown an overall decrease in the incidence of colorectal cancer despite contrasting increases in younger age groups. We examined whether these cohort trends are occurring in Canada. Age-specific trends in colon and rectal cancer incidence in Canada from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2012) were analyzed. We estimated annual percent changes (APC) with the Joinpoint Regression Program from the Surveillance Epidemiology, and End Results Program. Birth cohort effects were estimated using 5-year groups starting in 1888. Age-specific prevalence of class I, II and III obesity in Canada was examined from the National Population Health Survey (1994-2001) and the Canadian Community Health Survey (2001-2011). The reductions in CRC incidence among Canadians are limited to older populations. While reductions among younger age groups (20-29year olds (yo), 30-39yo and 40-50yo) were observed between 1969 and 1995, rates have returned to and surpassed historical levels (APCs 20-29yo colon cancer=6.24%, APCs 20-29yo rectal cancer=1.5%). Recent birth cohorts (1970-1990) have the highest incidence rate ratios ever recorded. Ecologic trends in obesity prevalence among these birth cohorts in Canada are suggestive of an impact on increasing incidence trends. Furthermore, obesity prevalence estimates suggest that these trends may continue to increase justifying further examination of the etiologic associations and biological impacts of excess adipose tissue among younger populations. While population-based screening of younger age groups deserves careful consideration, these concerning observed trends warrant public health action to address the growing obesity epidemic.

Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and < 35 kg/m) was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI > 35 kg/m) was associated with a 4.7-fold increase compared to normal-weight women (BMI < 25 kg/m). Increased central adiposity also increased endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.

The adenosine deaminases acting on RNA (ADARs) are double-stranded RNA (dsRNA) binding enzymes that catalyze RNA editing of cellular and viral dsRNAs by deamination, which converts adenosines into inosines (6,22,54). Inosine is recognized as a guanosine, and thereby deamination alters the sequence-or structure-specific recognition of RNAs, their translation, and, consequently, the amino acid sequences of several proteins. This process also affects noncoding RNA, and the modification of microRNA (miRNA) sequences is very important in the RNA interference (RNAi) pathway that regulates posttranscriptional gene expression (35,53,54). In vertebrate cells, there are three genes that code for the ADAR1, ADAR2, and ADAR3 proteins. The mammalian Adar1 gene encodes two forms of the ADAR1 protein: the interferon (IFN)-inducible ϳ150-kDa form (p150) found in both the cytoplasm and the nucleus and the constitutively expressed ϳ110-kDa form (p110) found only in the nucleus (40, 90). These two forms are generated through alternative promoters (one of which is IFN inducible) and alternative splicing of exon