Skip to Content
Discovering the causes of cancer and the means of prevention

Scientific Highlights November 2014 - February 2015

Recently Published DCEG Papers

Posted on February 24, 2015

Cancer Topics

Breast Cancer

Gene-Environment Interaction

COMMENTARY: Garcia-Closas M, Gunsoy NB, Chatterjee N. Combined associations of genetic and environmental risk factors: implications for prevention of breast cancer. J Natl Cancer Inst 2014;106 pii: dju305. doi:10.1093/jnci/dju305

Tamoxifen Effects on Mammographic Density

A study using data from Kaiser Permanente Northwest (1990-2008) showed that younger and older ER-positive breast cancer patients who experience large reductions in mammographic density following tamoxifen therapy initiation have an improved prognosis. (Nyante SJ, Sherman ME, Pfeiffer RM, et al. Prognostic significance of mammographic density change after initiation of tamoxifen for ER-positive breast cancer. J Natl Cancer Inst 2015; 107:E-pub Feb 6)

Terminal Duct Lobular Units

Terminal duct lobular units (TDLU) are the predominant origin of breast cancers. In an investigation using samples from the Susan G. Komen Tissue Bank, the authors found that select circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution, which offers new insights into breast carcinogenesis. (Khodr ZG, Sherman ME, Pfeiffer RM, et al. Circulating sex hormones and terminal duct lobular unit involution of the normal breast. Cancer Epidemiol Biomarkers Prev 2014;23:2765-2773).

Back to Cancer Topics

Cervical Cancer

Cervical Cancer Screening Clinical Guidance

CLINICAL COMMENTARY: Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol 2015 Feb;136:178-182. Published simultaneously in Gynecologic Oncology, Journal of Lower Genital Tract Disease, and Obstetrics & Gynecology.

HPV 16 Methyl-haplotypes and Cervical Precancer

The investigators developed and evaluated a next-generation bisulfite sequencing assay that assesses the degree of HPV 16 methylation to distinguish HPV 16 cervical precancer from HPV 16-positive transient infections, which can serve to identify women at high risk for cervical cancer. (Mirabello L, Frimer M, Harari A, et al. HPV 16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer. Int J Cancer 2015;136:E146-E153)

Multiple Biopsies at Colposcopy

The Biopsy Study is an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. Collection of additional lesion-directed biopsies during colposcopy increased detection of cervical cancer precursors, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy. (Wentzensen N, Walker JL, Gold MA, et al. Multiple biopsies and detection of cervical cancer precursors at colposcopy. J Clin Oncol 2014; E-pub Nov 24). Read more about multiple biopsies at colposcopy.

Single Dose HPV Vaccine Trial

COMMENTARY: Kreimer AR, Sherman ME, Sahasrabuddhe VV, Safaeian M. The Case for Conducting a Randomized Clinical Trial to Assess the Efficacy of a Single Dose of Prophylactic HPV Vaccines Among Adolescents. J Natl Cancer Inst 2015: Feb 2;107(3). pii: dju436. doi: 10.1093/jnci/dju436.

Back to Cancer Topics

Endometrial Cancer

Early Detection by DNA Hypermethylation

DNA hypermethylation in endometrial cancer tissues was also seen in vaginal pool DNA collected via intravaginal tampon, demonstrating the potential of this minimally-invasive specimen collection technique as an early detection tool for EC. (Bakkum-Gamez JN, Wentzensen N, Maurer MJ, et al. Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons. Gynecol Oncol 2015;E-pub Feb 10)

Infertility

A pooled analysis of 8153 endometrial cancer cases and 11 713 controls showed that nulliparity and infertility appear to independently contribute to endometrial cancer risk. (Yang HP, Cook LS, Weiderpass E, et al. Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2). Br J Cancer 2015;112:925-933)

Metabolic Syndrome

A case-control study within the SEER-Medicare linked database showed that, among women age 65 and older in the United States, metabolic syndrome and its component factors increased endometrial cancer risk similarly across endometrial cancer subtypes, and independent of overweight/obesity. (Trabert B, Wentzensen N, Felix AS, et al. Metabolic syndrome and risk of endometrial cancer in the united states: a study in the SEER-Medicare linked database. Cancer Epidemiol Biomarkers Prev 2014;24:261-267)

Back to Cancer Topics

Esophageal Cancer

Childhood Body Mass Index

A study linking data from the Copenhagen School Health Records Register and the Danish Cancer Registry showed that individuals with higher childhood body mass index were at elevated risk of esophageal adenocarcinoma, even though these cancers occurred many decades later in life. (Cook MB, Freedman ND, Gamborg M, et al. Childhood body mass index in relation to future risk of oesophageal adenocarcinoma. Br J Cancer 2015; 112:601-607)

Cytological Testing Using a Capsule Sponge Method

In a comparison with endoscopic examination, a capsule sponge method of collecting esophageal cytological specimens was a feasible, safe, and highly sensitive and specific method for diagnosing precancerous lesions of the esophagus in this population, with promising initial accuracy data for the detection of high-grade esophageal squamous dysplasia. (Roshandel G, Merat S, Sotoudeh M, et al. Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran. Br J Cancer 2014;111:2235-2241)

Vascular Epithelial Growth Factor A

A study that assessed the role of genetic markers in selected inflammation-related genes involved in wound healing found evidence for a potential role for vascular endothelial growth factor (VEGF)A, a gene in the development and progression of early precancerous lesions of esophagus. (Golozar A, Beaty TH, Gravitt PE, et al. Oesophageal squamous cell carcinoma in high-risk Chinese populations: Possible role for vascular epithelial growth factor A. Eur J Cancer 2014;50:2855-2865)

Back to Cancer Topics

Genetics

DNA Methylation of 8q24

Investigators found correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk. (Barry KH, Moore LE, Sampson J, et al. DNA methylation levels at chromosome 8q24 in peripheral blood are associated with 8q24 cancer susceptibility loci.Cancer Prev Res 2014;72:1282-1292)

9p21 and Multiple Cancers

In a study of single nucleotide polymorphisms (SNPs) in the 9p21 region, investigators identified several genetic variants associated with the risk of multiple cancers, suggesting that this region may contribute to a shared susceptibility across different cancer types. The study included data deposited in dbGaP from eight genome-wide association studies (GWAS), including studies of gastric, pancreatic, lung, breast, bladder, and prostate cancer and renal cell carcinoma and esophageal squamous cell carcinoma. (Li WQ, Pfeiffer RM, Hyland PL, et al. Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers. Carcinogenesis 2014;35:2698-2705)

Back to Cancer Topics

Head and Neck Cancers

HPV-Positive Head and Neck Cancers

COMMENTARY: Chaturvedi AK. Global burden of human papillomavirus-positive head and neck cancers. Lancet Oncol 2014;15:1282-1283

Back to Cancer Topics

Hormones

Breast, Ovarian, and Endometrial Cancer

COMMENTARY: Wentzensen N, Trabert B. Hormone therapy: short-term relief, long-term consequences. Lancet 2015; E-pub Feb 12

Back to Cancer Topics

Human Immunodeficiency Virus (HIV)

HIV-related Cancer in the U.S.

An estimated 7,760 new cancers were diagnosed in 2010 among the nearly 900,000 Americans known to be living with HIV infection, with  approximately half of these cancers (3,920) being in excess of what would be expected if HIV-infected people had the same cancer risk as the general population. The most common excess malignancies were non-Hodgkin lymphoma, Kaposi sarcoma, anal cancer, and lung cancer. (Robbins HA, Pfeiffer RM, Shiels MS, et al. Excess cancers among HIV-infected people in the United States. J Natl Cancer Inst 2015 Feb 7. 10.1093/jnci/dju503 [E-pub ahead of print]). Read more about HIV-related cancer in the U.S.

Back to Cancer Topics

Human Papillomavirus (HPV)

Cervical Cancer Screening Clinical Guidance

CLINICAL COMMENTARY: Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol 2015 Feb;136:178-182. Published simultaneously in Gynecologic Oncology, Journal of Lower Genital Tract Disease, and Obstetrics & Gynecology.

HPV-Positive Head and Neck Cancers

COMMENTARY: Chaturvedi AK. Global burden of human papillomavirus-positive head and neck cancers. Lancet Oncol 2014;15:1282-1283

HPV Type Replacement after Vaccination

COMMENTARY: Safaeian M, Rodriguez AC. Multiple human papillomavirus infections and type replacement-anticipating the future after human papillomavirus vaccination. Am J Epidemiol 2014;180:1076-1081

HPV 16 Methyl-haplotypes and Cervical Precancer

The investigators developed and evaluated a next-generation bisulfite sequencing assay that assesses the degree of HPV 16 methylation to distinguish HPV 16 cervical precancer from HPV 16-positive transient infections, which can serve to identify women at high risk for cervical cancer. (Mirabello L, Frimer M, Harari A, et al.  HPV 16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer. Int J Cancer 2015;136:E146-E153)

Interobserver Agreement of Cervical Specimen Immunohistochemistry

REVIEW: Reuschenbach M, Wentzensen N, Dijkstra MG, et al.p16INK4a immunohistochemistry in cervical biopsy specimens: A systematic review and meta-analysis of the interobserver agreement. Am J Clin Pathol 2014;142:767-772

Protection from Vulvar HPV Infection

An intention-to-treat analysis from the Costa Rica Vaccine Trial demonstrated comparable vaccine efficacy against vulvar and cervical HPV 16/18 four years following vaccination. (Lang Kuhs KA, Struijk L, Chen S, et al. Reduced prevalence of vulvar HPV 16/18 infection among women who received the HPV 16/18 bivalent vaccine: A nested analysis within the Costa Rica Vaccine Trial. J Infect Dis 2014;210:1890-1899)

Back to Cancer Topics

Leukemia

Myeloid Neoplasms after Solid Organ Transplantation

A study linking the U.S. Scientific Registry of Transplant Recipients with 15 population-based cancer registries found increased risk for myeloid neoplasms among 207,859 solid organ transplant recipients, supporting a role for immune dysfunction the etiology of these cancers. Overall survival following acute myeloid leukemia and myelodysplastic syndrome in this population was inferior to that of similar patients reported to U.S. cancer registries. (Morton LM, Gibson TM, Clarke CA, et al. Risk of myeloid neoplasms after solid organ transplantation. Leukemia 2014;28:2317-2323)

Back to Cancer Topics

Liver Cancer

C-Reactive Protein

Using data from the Linxian Nutrition Intervention Trials cohort, investigators showed that higher baseline serum concentrations of C-reactive protein, a marker of systemic inflammation, were associated with subsequent incidence of liver cancer and death from chronic liver disease. (Chen W, Wang JB, Abnet CC,  et al. Association between C-reactive protein, incident liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: A Nested Case-Control Study. Cancer Epidemiol Biomarkers Prev 2015;24:386-392).

Statin Use

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely prescribed to reduce cholesterol levels and have been associated with reduced risk of liver cancer, based on data from regions of the world with high liver cancer incidence rates. The current study, which examined the statins-liver cancer relationship in a low-rate region, found that statin use was associated with a reduced risk of liver cancer overall, and particularly among persons with liver disease and persons with diabetes. (McGlynn KA, Hagberg K, Chen J, et al. Statin use and risk of primary liver cancer in the Clinical Practice Research Datalink. J Natl Cancer Inst 2015;E-pub Feb 26)

Back to Cancer Topics

Lung Cancer

Indoor Air Pollution

The authors report the association of indoor air pollution from poor kitchen ventilation of coal combustion with the risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. (Kim C, Gao YT, Xiang YB, et al. Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China. Int J Cancer 2015;136:632-638)

Back to Cancer Topics

Lymphoma

Genetic Variation in Human Leukocyte Antigen Complex

A two-stage GWAS of 1,281 marginal zone lymphoma (MZL) cases and 7,127 controls of European ancestry identified two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk, providing the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility. (Vijai J, Wang Z, Berndt SI, et al. A genome-wide association study of marginal zone lymphoma shows association to the HLA regionNat Commun 2015;Jan 8;6:5751. doi: 10.1038/ncomms6751.

Back to Cancer Topics

Methods

COMMENTARY: Panagiotou OA, Wacholder S. How big is that interaction (in my community)—and in which direction? Am J Epidemiol 2014;180:1150-1158

Back to Cancer Topics

Ovarian Cancer

Novel Susceptibility Loci

The authors carried out a meta-analysis of 11 million genetic variants with risk of epithelial ovarian cancer from 15,437 cases unselected for family history, 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and 30,845 controls. This new study design yielded increased statistical power, leading to the discovery of six new susceptibility loci. (Kuchenbaecker KB, Ramus SJ, Tyrer J, et al. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nat Genet 2015;47:164-171)

Back to Cancer Topics

Pancreatic Cancer

Advanced Glycation End Products

Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in raw foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes. In an analysis based on a published food database and data from the prospective NIH-AARP Diet and Health Study, consumption of dietary N(ϵ)-(carboxymethyl)lysine AGE, one of the major biologically and chemically well-characterized AGE markers, was associated with modestly increased risk of pancreatic cancer in men; it may partially explain the positive association between red meat and pancreatic cancer. (Jiao L, Stolzenberg-Solomon R, Zimmerman TP, et al. Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study. Am J Clin Nutr 2015;101:126-134)

Tumor Suppressor Function for HNF1A

The authors used a genome-wide approach to profile gene expression changes between pancreatic ductal adenocarcinoma tissue and normal derived pancreatic samples. An examination of these data in the context of gene expression sub-networks implicated a novel, central role for the transcription factor HNF1A in key gene regulatory programs of the exocrine pancreas, and functional experiments suggest HNF1A down-regulation benefits proliferation and survival of pancreatic tumor cells. (Hoskins JW, Jia J, Flandez M, et al. Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A. Carcinogenesis 2014;35:2670-2678)

Back to Cancer Topics

Physical Activity

Sedentary Behavior and Body Mass Index

A report from the prospective NIH-AARP Diet and Health Study showed that more sitting and more television viewing at baseline were associated with additional increases in body mass index (BMI) over time, and the association was stronger at the upper BMI percentiles. (Mitchell JA, Bottai M, Park Y, et al. A prospective study of sedentary behavior and changes in the body mass index distribution. Med Sci Sports Exerc 2014;46:2244-2252)

Sleep Duration and Mortality

In the NIH-AARP Diet and Health Study, investigators found that short sleep duration predicted higher mortality, particularly CVD mortality, among overweight and obese people. (Xiao Q, Keadle SK, Hollenbeck AR, et al. Sleep duration and total and cause-specific mortality in a large US cohort: interrelationships with physical activity, sedentary behavior, and body mass index. Am J Epidemiol 2014;180:997-1006)

Back to Cancer Topics

Prostate Cancer

Toll-like receptor 4

REVIEW: Weng PH, Huang YL, Page JH, et al. Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: A systematic review and meta-analysis. PLoS One 2014;9:e110569

Back to Cancer Topics

Second Cancers

Obesity-associated Cancers after Colorectal Cancer

Using data from five prospective cohorts, investigators found that colorectal cancer survivors who were overweight or obese before diagnosis had increased risk of second obesity-associated cancers compared with survivors with normal weight. The risks were similar in magnitude to those observed for first cancers in this population, suggesting increased prevalence of overweight or obesity, rather than increased susceptibility, may contribute to elevated second cancer risks in colorectal cancer survivors compared with the general population. (Gibson TM, Park Y, Robien K, et al. Body mass index and risk of second obesity-associated cancers after colorectal cancer: A pooled analysis of prospective cohort studies. J Clin Oncol 2014;32:4004-4011)

Smoking-Associated Cancers among Cancer Survivors

This report shows that smoking before a first cancer diagnosis of lung (stage I), bladder, kidney, or head/neck cancers increased the risk of second primary smoking-associated cancers. (Shiels MS, Gibson T, Sampson J, et al. Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers. J Clin Oncol 2014;32:3989-3995)

Back to Cancer Topics

Telomere Biology

Telomere length and Survival after Transplant

Longer donor leukocyte telomere length was associated with increased five-year survival in patients who received hematopoietic cell transplant for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival (Gadalla SM, Wang T, Haagenson M, et al. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia. JAMA 2015;313:594-602). Read more about telomere length and survival after transplant.

Back to Cancer Topics