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Discovering the causes of cancer and the means of prevention

Scientific Highlights March - June 2018

, by DCEG Staff

All-Cause Mortality

Physical Activity

Two reports based on the National Health and Nutrition Examination Survey 2003-2006 accelerometer records in adults and mortality data collected through 2011 evaluated benefits of types of physical activity in relation to all-cause mortality. The total volume of physical activity, rather than intensity, seems to be the key driver in reducing the risk for all‐cause mortality. The difference in mortality benefits associated with moderate‐to‐vigorous physical activity are only modest in comparison to light physical activity after accounting for the volume of physical activity. In addition, sporadic and bouted moderate‐to‐vigorous physical activity was similarly and strongly associated with mortality risk. Mortality risk reductions associated with moderate‐to‐vigorous physical activity are independent of how activity is accumulated. (Saint-Maurice PF, Troiano RP, Berrigan D, et al. Volume of light versus moderate-to-vigorous physical activity: Similar benefits for all-cause mortality? J Am Heart Assoc 2018; Epub Apr 2. Saint-Maurtice PF, Troiano RP, Matthews CE, Kraus WE. Moderate-to-vigorous physical activity and all-cause mortality: do bouts matter? J Am Heart Assoc 2018; Epub Mar 22.) Find more information in “Get 150 minutes/week of moderate physical activity: It doesn’t matter how” in Research News & Highlights.


Inflammatory Proteins

Investigators examined circulating inflammatory proteins and overall survival among gallbladder cancer (GBC) cases from population-based studies in Shanghai and Chile. Of 49 evaluable proteins, eight were significantly associated with overall survival among the Shanghai cases: seven were associated with a poorer survival, and the highest levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were associated with an increase in survival. No substantial difference in the magnitude of the association was observed between early- and late-stages of GBC. Of seven proteins, five were validated in the patients from Chile. Reducing inflammation and targeting pathways associated with increased survival might improve outcomes. The potential for using a TRAIL-related anticancer drug for gallbladder cancer treatment merits further investigation. (Liu Z, Kemp TJ, Gao YT, et al. Circulating levels of inflammatory proteins and survival in patients with gallbladder cancer. Sci Rep 2018)


Physical Activity

Using data from the NIH-AARP Diet and Health Study cohort, investigators examined physical activity patterns over the life course in relation to risk of hepatocellular carcinoma. Compared to persons with consistently low physical activity patterns, those who maintained activity levels over time had a 26-36% lower risk of liver cancer and those who increased physical activity over time had no associations with risk, while those who decreased activity over time had a non-significantly higher risk of liver cancer. The results suggest that sustained physical activity is associated with lower risk of hepatocellular carcinoma, while increasing physical activity later in life may not yield the same benefit. (Arem H, Loftfield E, Saint-Maurice PF, et al. Physical activity across the lifespan and liver cancer incidence in the NIH-AARP Diet and Health Study cohort. Cancer Med 2018; Epub Mar 13.)

Tobacco and Alcohol

While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Data from the Liver Cancer Pooling Project, a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410), showed that current smoking was associated with 47–86% increased HCC and ICC risks, while increasing years since smoking cessation was associated inversely with HCC risk only. Heavy alcohol consumption was associated with 68–87% increased HCC and ICC risks. Light or moderate alcohol consumption (i.e., <3 drinks per day) was associated with a decreased HCC, but not ICC, risk. A positive multiplicative interaction was observed between heavy alcohol consumption and diabetes with HCC risk. (Petrick JL, Campbell PT, Koshiol J, et al. Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project. Br J Cancer 2018; Epub Mar 9.)


Microbiome Stability

Identifying which alterations of microbial populations or functions contribute to disease, treatment response, or remission will hinge on comparisons of specimens that are collected prospectively. Researchers conducting prospective studies need to consider temporal variation in microbiome measurements. Analyses were performed on 16S rRNA profiles in paired specimens from various body sites separated by six months from three studies. Interclass correlation coefficients for temporal stability were generally 0.5 or below for the majority of the phylum-level relative abundances and alpha-diversity metrics across different types of specimens. This finding implies that even nominally significant associations with these unstable metrics should be interpreted with caution and that sample sizes need to be quite large for these types of analyses. In contrast, unweighted UniFrac, one measure of beta diversity, was relatively stable not only for stool specimens but also for oral, oropharynx, and vagina specimens. (Sinha R, Goedert JJ, Vogtmann F, et al. Quantification of human microbiome stability over six months: Implications for epidemiologic studies. Am J Epidemiol 2018; Epub Mar 28)

Whole-Genome Amplified DNA

The recommended genomic DNA input requirements for whole-genome single nucleotide polymorphism microarrays can limit the scope of molecular epidemiological studies. Investigators performed a large-scale evaluation of whole-genome amplified DNA as input into high-density, whole-genome Illumina® Infinium® SNP microarray. Overall, 6,622 DNA samples from 5,970 individuals were obtained from three distinct biospecimen sources and genotyped using gDNA and/or wgaDNA inputs. When genotypes from the same individual were compared with standard, native gDNA input amount, there was 99.94% mean concordance with wgaDNA input. The results demonstrate that carefully conducted studies with wgaDNA inputs can yield high-quality genotyping results. These findings should enable investigators to consider expansion of ongoing studies using high-density SNP microarrays, currently challenged by small amounts of available DNA. (Dagnall CL, Morton LM, Hicks BD, et al. Successful use of whole genome amplified DNA from multiple source types for high-density Illumina SNP microarrays. BMC Genomics 2018;19:182)


Serum Interleukin-16

To explore the role of inflammation in prostate cancer risk, the association between pre-diagnostic serum levels of interleukin-16 (IL-16), an important pleiotropic cytokine, and prostate cancer risk was evaluated in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Although no association between pre-diagnostic IL-16 and prostate cancer overall was observed among Caucasians, a significantly increased risk of high-grade prostate cancer, defined as Gleason ≥ 7, was observed with increasing levels of IL-16. Among Caucasian men with a history of gonorrhea, elevated IL-16 levels were associated with an increased risk of prostate cancer (OR 3rd vs. 1st tertile = 3.64) but no association was seen among those without a history of gonorrhea. No associations were observed among African-Americans. (Moore A, Huang WY, Danforth K, et al. Prospective evaluation of serum IL-16 and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Causes Control 2018 May; Epub Mar 28)


Childhood Height

Increased adult stature has been associated with risk of testicular germ cell tumors (TGCT) in a number of studies. Whether childhood stature is also associated with TGCT is unclear as no studies of measured childhood height and TGCT have been reported. Thus, associations between TGCT in adulthood and childhood height and growth between ages 7 and 13 years were examined in a cohort from the Copenhagen School Health Records Register. Analyses of this large prospective study showed that measured childhood height was positively associated with risk of TGCT. In a categorical analysis, the shortest boys were at the lowest risk of subsequently developing TGCT, whereas there was no significant association with risk among the tallest boys. Growth between ages 7 and 13 years was not associated with risk. Results were similar for seminomas and nonseminomas. These findings suggest that risk of TGCT in adulthood was already determined by age 7 years. (McGlynn KA, Petrick JL, Gamborg M, et al. Childhood height and risk of testicular germ cell tumors in adulthood. Int J Cancer 2018; Epub Mar 6)

Upper Gastrointestinal Tract

Vitamin Supplementation

A beneficial effect of supplementation with selenium, vitamin E, and beta-carotene was observed on total and cancer mortality in the Linxian Nutritional Intervention Trial, and it endured for 10 years post intervention. This report evaluated the durability of these findings after 25 years of follow-up. Through 2016, the interventions showed no effect on total mortality. The previously reported protective effect of Factor D (selenium/vitamin E/beta-carotene) against total mortality was lost 10 years post-intervention. The protective effect of Factor D for gastric cancer was attenuated, but a newly apparent protective effect against esophageal cancer was found for Factor B (riboflavin/niacin). Protective effects were found in people younger than age 55 years at baseline against non-upper gastrointestinal cancer death for Factor A (retinol/zinc) and against death from stroke for Factor C (vitamin C/molybdenum). In contrast, increased risk of esophageal cancer was found when the intervention began after age 55 years for Factors C and D. The authors concluded that multiyear nutrition intervention is unlikely to have a meaningful effect on mortality more than a decade after supplementation ends, even in a nutritionally deprived population. Whether sustained or repeat intervention would provide longer effects needs further investigation. (Wang SM, Taylor PR, Fan JH, et al. Effects of nutrition intervention on total and cancer mortality: 25-year post-trial follow-up of the 5.25-year Linxian Nutrition Intervention Trial. J Natl Cancer Inst 2018; Epub Apr 3)

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