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Discovering the causes of cancer and the means of prevention

Scientific Highlights March - June 2015

Posted on September 09, 2015

Cancer Topics

All Cancers

Immunosuppression and Stage at Diagnosis

The authors used data on 15 cancer types from U.S. cancer registries linked with HIV and transplant registries and observed that bladder cancer and melanoma were more likely to be diagnosed at a nonlocal stage in both HIV-infected individuals and transplant recipients, suggesting a role for immunosuppression in their progression. A shift for some common cancers toward later stage at diagnosis in HIV-infected individuals but earlier stage in transplant recipients suggests differential access to medical care or surveillance. (Shiels MS, Copeland G, Goodman MT, et al.Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients. Cancer 2015;121:2063-2071)

Organ Transplantation

Induction immunosuppression is a mainstay to prevent organ rejection after transplantation. Using a linkage of data on U.S. transplantation procedures and cancer incidence from registries, the authors found muromonab-CD3 was associated with increased risk for non-Hodgkin lymphoma (NHL) and alemtuzumab was associated with increased risk for NHL, colorectal cancer, and thyroid cancer. Polyclonal induction was associated with increased melanoma risk. The findings highlight the relative safety of the most common induction therapies with regard to cancer risk; the need for surveillance of patients treated with alemtuzumab; and the possible role for increased melanoma screening for patients treated with polyclonal anti-T-cell induction. (Hall EC, Engels EA, Pfeiffer RM, Segev DL. Association of antibody induction immunosuppression with cancer after kidney transplantation. Transplantation 2015;99:1051-1057)

Tobacco Attributable Risk

Based on data from the National Health Interview Study, the Cancer Prevention Study-II, and the Pooled Contemporary Cohort, the population attributable fraction (PAF) for active cigarette smoking was 28.7% when estimated conservatively, including only deaths from the 12 cancers currently established as caused by smoking by the U.S. Surgeon General. The PAF was 31.7% when estimated more comprehensively, including excess deaths from all cancers. (Jacobs EJ, Newton CC, Carter BD, et al. What proportion of cancer deaths in the contemporary United States is attributable to cigarette smoking? Ann Epidemiol 2015;25:179-182.e1)

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Bladder Cancer

Selenium and Smoking

Selenium has been linked to a reduced risk of bladder cancer in some studies. An evaluation in the New England Bladder Cancer Case-Control Study, based on careful analysis of a comprehensive smoking history and selenium levels measured in toenail samples, saw no evidence of an association between selenium levels and bladder cancer. (Beane Freeman LE, Karagas MR, Baris D, et al. Is the inverse association between selenium and bladder cancer due to confounding by smoking? Am J Epidemiol 2015;181:488-495)

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Bone Cancer

Genetic Susceptibility and Metastasis

A multi-stage genome-wide association study of 935 osteosarcoma patients identified a SNP, rs7034162, in NFIB significantly associated with metastasis at diagnosis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry. (Mirabello L, Koster R, Moriarity BS, et al. A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma. Cancer Discov 2015;Epub Jun 17)

TP53 Tumor Suppressor Gene

Investigators sequenced the tumor suppressor gene, TP53, among 765 osteosarcoma patients. A higher than expected prevalence of TP53 mutations, particularly those known to be associated with the Li-Fraumeni syndrome as well some other rare novel changes, were observed among young osteosarcoma patients, but not older patients. (Mirabello L, Yeager M, Mai PL, et al. Germline TP53 variants and susceptibility to osteosarcoma. J Natl Cancer Inst 2015; E-pub April 20). Read more about inherited TP53 variations and susceptibility to osteosarcoma.

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Brain Cancer

Genomic and Somatic Integrative Analyses

The authors confirmed strong association of rs78378222:A>C, a rare germline single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma and integrative analyses on data for glioblastoma multiforme from the Cancer Genome Atlas. Their findings suggest a rare risk allele (C) for rs78378222 disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma. (Wang Z, Rajaraman P, Melin BS, et al. Further confirmation of germline glioma risk variant rs78378222 in TP53 and its implication in tumor tissues via integrative analysis of TCGA data. Human Mutat 2015;36:684-688)

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Breast Cancer

Estrogen Metabolism

REVIEW: Ziegler RG, Fuhrman BJ, Moore SC, Matthews CE. Epidemiologic studies of estrogen metabolism and breast cancer. Steroids 2015;99(Pt A):67-75.

Genetic Susceptibility for In Situ Breast Cancer

This study, based on genotyping data from NCI’s Breast and Prostate Cancer Cohort Consortium (BPC3), showed that several of the known breast cancer susceptibility loci are risk factors for both in situ and invasive breast cancer, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific breast cancer in situ susceptibility locus. (Campa D, Barrdahl M, Gaudet MM, et al. Genetic risk variants associated with in situ breast cancer. Breast Cancer Res 2015;17:82)

Genetic Variation and Survival

A meta-analysis of 37,954 breast cancer patients, including 2,900 deaths from breast cancer, identified a new locus (rs2059614 at 11q24.2) associated with survival in women diagnosed with estrogen receptor (ER)-negative tumors. A second locus (rs148760487 at 2q24.2) was associated with survival among ER-positive and ER-negative case patients, but the finding was less robust than for rs2059614. (Guo Q, Schmidt MK, Kraft P, et al. Identification of novel genetic markers of breast cancer survival. J Natl Cancer Inst 2015;107:doi: 10.1093/jnci/djv081)

Hormones and Male Breast Cancer

Using prediagnostic serum from 101 male breast cancer cases and 217 controls, serum levels of androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association (highest quartile: odds ratio = 2.5, trend P = .06). (Brinton LA, Key TJ, Kolonel LN, et al. Prediagnostic sex steroid hormones in relation to male breast cancer risk. J Clin Oncol 2015;33:2041-2050)


This pilot study of 48 postmenopausal breast cancer cases (pretreatment) and 40 controls reported that postmenopausal women with breast cancer have altered composition and estrogen-independent low diversity of their gut microbiota. Whether these affect breast cancer risk and prognosis is unknown. (Goedert JJ, Jones G, Hua X, et al. Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: A population-based case-control pilot study. J Natl Cancer Inst 2015;107:Epub Jun 1)

Novel Genetic Susceptibility Loci

The investigators performed a meta-analysis of 11 genome-wide association studies, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). They generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and identified 15 new loci associated with breast cancer. Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, they identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1. (Michailidou K, Beesley J, Lindstrom S, et al. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet 2015;47:373-380)

Prognostic Signature for ER-Positive Cancer

A methylaion expression index (MEI) was developed through an integrated analysis of tumor expression markers, DNA methylation, and mRNA data. Low MEI was related to decreased survival among women with ER-positive breast cancer in a study conducted in Poland and in four independent datasets totaling over 2500 ER-positive breast cancers. (Figueroa J, Yang H, Garcia-Closas M, et al. Integrated analysis of DNA methylation, immunohistochemistry and mRNA expression, data identifies a methylation expression index (MEI) robustly associated with survival of ER-positive breast cancer patients. Breast Cancer Res Treat 2015;150:457-466)

Risk Prediction based on Genetic Variants

The authors constructed a 77 single nucleotide polymorphism (SNP) polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) in a study of 33,673 women with breast cancer and 33,381 controls, both of European origin. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile. The ORs for ER-positive and ER-negative disease were 3.7 and 2.8, respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. (Mavaddat N, Pharoah PD, Michailidou K, et al. Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst 2015;107: doi: 10.1093/jnci/djv036)

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Cervical Cancer

HPV Genotyping in Screening

To assess the possible value of HPV 16/18 typing in determining management of cervical screening outcomes, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with the cobas® HPV Test ("cobas", Roche Molecular Systems), which detects HPV 16 and HPV 18 individually, as well as a 12 other high-risk HPV types. The cobas results showed excellent agreement with an established method, the LINEAR ARRAY HPV Genotyping Test (LA, Roche Molecular Systems), and demonstrated that HPV 16 typing is useful in the management of HPV-positive/cytology-negative women in co-testing, all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US (atypical squamous cells of undetermined significance). (Schiffman M, Boyle S, Raine-Bennett T, et al. The role of human papillomavirus (HPV) genotyping in cervical cancer screening: A large-scale evaluation of the cobas HPV test. Cancer Epidemiol Biomarkers Prev 2015;Epub June 18)

HPV Vaccine

Data from the Costa Rica Vaccine Trial and the PATRICIA Trial show that four years after vaccination of women aged 15-25 years, one and two doses of the HPV 16/18 vaccine seem to protect against cervical HPV 16/18 infections similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection for other HPV types. (Kreimer AR, Struyf F, Del Rosario-Raymundo MR, et al. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: Combined analysis of data from the Costa Rica Vaccine and PATRICIA trials. Lancet Oncol 2015;16:775-786)

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Colorectal Cancer

Reproductive and Hormonal Factors

Although use of menopausal hormone therapy and some reproductive factors have been associated with colorectal cancer risk, the relationship between these factors and survival after colorectal cancer diagnosis are unclear. In this study of 2,053 women with colorectal cancer, reproductive and menstrual factors were not associated with mortality, while current, but not former, baseline menopausal hormone therapy use was associated with lower all-cause and colorectal cancer mortality risks. (Arem H, Park Y, Felix AS, et al. Reproductive and hormonal factors and mortality among women with colorectal cancer in the NIH-AARP Diet and Health Study. Br J Cancer 2015;113:562-568)

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Endometrial Cancer

Tubal Ligation

Tubal ligation in years prior to diagnosis is associated with lower stage and mortality among women with aggressive endometrial carcinomas, suggesting transtubal spread of cancer cells is clinically important. (Felix AS, Brinton LA, McMeekin DS, et al. Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/ Gynecologic Oncology Group 210 Trial. J Natl Cancer Inst 2015; Epub June 18)

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Esophageal Cancer


REVIEW: Abnet CC, Corley DA, Freedman ND, Kamangar F. Diet and upper gastrointestinal malignancies. Gastroenterology 2015;148:1234-1243.

Dietary Intake of Minerals

Higher dietary intake of calcium and zinc were associated with a lower risk of esophageal squamous cell carcinoma in a high-risk region of Iran. (Hashemian M, Poustchi H, Abnet CC, et al. Dietary intake of minerals and risk of esophageal squamous cell carcinoma: Results from the Golestan Cohort Study. Am J Clin Nutr 2015; 102:102-108)

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Carrier Frequency of RTEL1 among Ashkenazi Jews

Hoyeraal-Hreidarsson syndrome (HH) is a clinically severe variant of dyskeratosis congenita (DC), characterized by cerebellar hypoplasia, microcephaly, intrauterine growth retardation, and severe immunodeficiency, in addition to features of DC. Germline mutations in the RTEL1 gene have recently been identified as causative of HH. In this study, the carrier frequency for c.3791G>A (p.R1264H) was higher than expected, 1% in the Ashkenazi Orthodox and 0.45% in the general Ashkenazi Jewish population. Haplotype analyses suggested the presence of a common founder. The authors recommend that the c.3791G>A RTEL1 mutation be considered for inclusion in carrier screening panels in the Ashkenazi population. (Fedeick AM, Shi L, Jalas C. Carrier screening of RTEL1 mutations in the Ashkenazi Jewish population. Clin Genet 2015;88:177-181)

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Human Papillomavirus


REVIEW: Schiffman M, Wentzensen N. Issues in optimising and standardising the accuracy and utility of the colposcopic examination in the HPV era. Ecancermedicalscience 2015; Apr 29 doi: 10.3332/ecancer.2015.530. eCollection 2015.

Endpoints for Future Trials

REVIEW: Lowy DR, Herrero R, Hildesheim A, et al. Primary endpoints for future prophylactic human papillomavirus vaccine trials: Towards infection and immunobridging. Lancet Oncol 2015;16:e226-e233.

Gender and Anatomic Site of Infection

REVIEW: Giuliano AR, Nyitray AG, Kreimer AR, et al. EUROGIN 2014 roadmap: Differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection. Int J Cancer 2015:136:2752-2760.

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Inherited Bone Marrow Failure Syndromes

Endocrine Disorders in Fanconi Anemia

REVIEW: Petryk A, Kanakatti Shankar R, Giri N, et al. Endocrine disorders in Fanconi anemia: recommendations for screening and treatment. J Clin Endocrinol Metab 2015;100:803-811.

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Kidney Cancer


Data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial showed alcohol consumption is associated with reduced renal cell carcinoma risk in both men and women, regardless of the type of alcoholic beverage. The inverse association with consumption was apparent for ever smokers but not among never smokers. (Karami S, Daugherty SE, Purdue MP. A prospective study of alcohol consumption and renal cell carcinoma risk. Int J Cancer 2015;137:238-242)

Genetic Susceptibility

The authors conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). They used a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. They observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. One SNP, rs1063355, associated with HLA-DQB1 expression, was significant in the original populations and a validation GWAS dataset. (Shu X, Purdue MP, Ye Y, et al. Multilevel-analysis identify a cis-expression quantitative trait locus associated with risk of renal cell carcinoma. Oncotarget 2015;6:4097-4109)


The authors found an association between LINE1 methylation in blood DNA and renal cell carcinoma risk in male smokers. The analysis utilized pre-diagnostic blood DNA from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The association was not observed for women. (Karami S, Andreotti G, Liao LM, et al. LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk. Epigenetics 2015;10:282-292)

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Juvenile Myelomonocytic Leukemia

The authors report an incompletely penetrant Casitas B-lineage lymphoma proto-oncogene (CBL) Y371C mutation discovered by whole-exome sequencing in three individuals with juvenile myelomonocytic leukemia (JMML) in a large pedigree with 35 years of follow-up. Protein structural modeling revealed that the Y371C mutation abrogated the ability of the CBL protein to adopt a conformation that is required for ubiquitination. The penetrance of the CBL Y371C mutation was 30% for JMML and 40% for all leukemia. Of the eight mutation carriers in the family with available photographs, only one had significant dysmorphic features; the investigators found no evidence of a clinical phenotype consistent with a "CBL syndrome". (Pathak A, Pemov A, McMaster ML, et al. Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family. Hum Genet 2015;134:775-787)

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Liver and Biliary Cancer


In a pilot study conducted in Chile, gallbladder cancer cases were significantly more likely to have detectable aflatoxin B1-lysine adducts in plasma than controls with gallstones (odds ratio [OR], 9.4) or community controls (OR, 13.2). (Nogueira L, Foerster C, Groopman J, et al. Association of aflatoxin with gallbladder cancer in Chile. JAMA 2015;313:2075-2077)

Coffee Drinking

Data from the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, showed reduced risk of incident hepatocellular carcinoma associated with coffee drinking. The effect was stronger among women and for caffeinated coffee. There was no relationship between coffee consumption and intrahepatic cholangiocarcinoma. (Petrick JL, Freedman ND, Graubard BI, et al. Coffee consumption and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by sex: The Liver Cancer Pooling Project. Cancer Epidemiol Biomarkers Prev 2015; Epub Jun 30)

Global Patterns

REVIEW: McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: An emphasis on demographic and regional variability. Clin Liver Dis 2015;19:223-238.

Reproductive Factors and Exogenous Hormone Use

In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, the risk of hepatocellular carcinoma was associated with a history of bilateral oophorectomy, but not with use of oral contraceptives. (McGlynn KA, Sahasrabuddhe VV, Campbell PT, et al. Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project. Br J Cancer 2015;E-pub Mar 5)

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Lung Cancer

Biomass Fuel

REVIEW: Bruce N, Dherani M, Liu R, et al. Does household use of biomass fuel cause lung cancer? A systematic review and evaluation of the evidence for the GBD 2010 study. Thorax 2015;70:433-441.

Indoor Air Pollution

REVIEW: Josyula S, Lin J, Xue X, et al. Household air pollution and cancers other than lung: A meta-analysis. Environ Health 2015;14:24 doi:10.1186/s12940-015-0001-3.

Indoor Air Pollution and Genetic Susceptibility

In a study of lung cancer among never smoker women in Southeast Asia, the risk associated with household coal exposure varied with the respective alleles for two single nucleotide polymorphisms (SNPs): HLA Class II rs2395185 and TP63 rs4488809 (rs4600802). The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations. (Hosgood HD 3rd, Song M, Hsiung CA, et al. Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA). Hum Genet 2015;134:333-341)

Telomere Length

The authors examined a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Aggregations of the seven variants were highly associated with lung cancer risk with the direction of the associations indicating that longer telomere length, as predicted by higher telomere-length-associated genetic risk score, is a risk factor for lung cancer. Although the telomere-length-associated variants explained only a fraction of the variation in telomere length, the associations suggest genetic effects tagged by these variants are important for lung cancer risk. (Machiela MJ, Hsiung CA, Shu XO, et al. Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: A report from the female lung cancer consortium in Asia. Int J Cancer 2015;137:311-319)

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Autoimmune Conditions

In a pooled analysis of 8,692 non-Hodgkin lymphoma (NHL) cases and 9,260 controls from 14 studies, autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio [OR] = 3.1), and marginal zone lymphoma (OR = 5.8); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.1). There were also interactions with immunity-related single nucleotide polymorphisms for B-cell mediated autoimmune conditions across major B-cell NHL subtypes and follicular lymphoma. (Wang SS, Vajdic CM, Linet MS, et al. Associations of non-Hodgkin lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci. Am J Epidemiol 2015;181:406-421)

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Increasing the Power of Case-Control Studies

The authors developed a statistical procedure that improves the efficiency of the logistic regression model for a case-control study by utilizing auxiliary information on covariate-specific disease prevalence via a series of unbiased estimating equations. They adopted empirical likelihood for statistical inference, and demonstrated its advantages through simulation and an application. (Qin J, Zhang H, Li P, et al. Using covariate-specific disease prevalence information to increase the power of case-control studies. Biometrika 2015;102:169-180)

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Attributable Fraction

REVIEW: Purdue MP, Hutchings SJ, Rushton L, Silverman DT. The proportion of cancer attributable to occupational exposures. Ann Epidemiol 2015;25:188-192.

Diesel Exhaust Exposure

The International Agency for Research on Cancer recently classified diesel engine exhaust as a Group I carcinogen based largely on its association with lung cancer. The authors conducted a cross-sectional molecular epidemiology study in a diesel engine truck testing facility that showed an association of diesel exposure with higher levels of lymphocytes that play a key role in the inflammatory process, which is increasingly recognized as contributing to the etiology of lung cancer. (Lan Q, Vermeulen R, Dai Y, et al. Occupational exposure to diesel engine exhaust and alterations in lymphocyte subsets. Occup Environ Med 2015;72:354-359)

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Oropharyngeal Cancer

Sexual Behaviors and HPV

Data from the U.S. National Health and Nutritional Examination Surveys (NHANES) 2009-2012 suggest that the higher burden of oral oncogenic HPV infections and HPV-positive oropharyngeal cancers among men than women arises in part from higher number of lifetime sexual partners and stronger associations with sexual behaviors among men. (Chaturvedi AK, Graubard BI, Broutian T, et al. NHANES 2009-2012 Findings: Association of sexual behaviors with higher prevalence of oral oncogenic human papillomavirus infections in U.S. men. Cancer Res 2015;75:2468-2477)


EDITORIAL: Chaturvedi AK. Tonsillectomy and Risk of Oropharyngeal Cancer: Implications for Research and Prevention. Cancer Prev Res (Phila) 2015;8:577-579.

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Ovarian Cancer

Fallopian Tube

COMMENTARY: Greene MH, Mai PL. The fallopian tube: From back stage to center stage. Cancer Prev Res (Phila) 2015; E-pub Mar 23.

Genetic Susceptibility for Mucinous Ovarian Carcinoma

An analysis of 1,644 mucinous ovarian carcinomas cases and 21,693 controls with imputation identified three new significant risk associations: rs752590 at 2q13, rs711830 at 2q31.1, and rs688187 at 19q13.2. The authors identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian tumors and for PAX8 at 2q13 in colorectal tumors. Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. (Ovarian Cancer Association Consortium, Australian Cancer Study, Australian Ovarian Cancer Study Group. Genome-wide significant risk associations for mucinous ovarian carcinoma. Nat Genet 2015;47:888-897)

Nitrate and Nitrite Ingestion

In an analysis within the Iowa Women’s Health Study, high nitrate levels in public drinking water and private well use was associated with increased ovarian cancer risk among postmenopausal women. Dietary nitrate ingestion was not associated with increased risk. (Inoue-Choi M, Jones RR, Anderson KE, et al. Nitrate and nitrite ingestion and risk of ovarian cancer among postmenopausal women in Iowa. Int J Cancer 2015;137:173-182)

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Pancreatic Cancer

Genome-wide Association Study

A genome-wide association study of 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in nine studies from North America, Central Europe and Australia identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, 7p13 (SUGCT, rs17688601), and 3q29 (TP63, rs9854771). A significant association was also detected at 2p13.3 (ETAA1, rs1486134), a region with previous suggestive evidence in Han Chinese. (Childs EJ, Mocci E, Campa D, et al. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet 2015; Epub Jun 22)

Risk Prediction Models

COMMENTARY: Wentzensen N, Eldridge RC. Clinical utility of prediction models for rare outcomes-The example of pancreatic cancer. Am J Epidemiol 2015;182:35-38.


Through an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia, the authors identified independent significant associations with variants in TERT, rs2853677 and rs401681. (Campa D, Rizzato C, Stolzenberg-Solomon R, et al. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. Int J Cancer 2015; Epub May 4)

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Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort. Updated diazinon exposure and cancer incidence information in the AHS provides additional evidence of an association with lung cancer risk and identifies new links to kidney cancer and aggressive prostate cancer. (Jones RR, Barone-Adesi F, Koutros S, et al. Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis. Occup Environ Med 2015;72:496-503) (NOTE: This study contributed to the recent IARC classification of diazinon as a Group 2a [probable] carcinogen.)

Nonoccupational Exposure among Women

REVIEW: Deziel NC, Friesen MC, Hoppin JA, et al. A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas. Environ Health Perspect 2015;123:515-524.

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Physical Activity

Physical Activity and Measurement Error

COMMENTARY: Arem H, Keadle SK, Matthew CE. Invited commentary: Meta-physical activity and the search for the truth. Am J Epidemiol 2015;181:656-658.

Physical Activity and Mortality

Using data from the NCI Cohort Consortium, the authors quantified the dose-response association between leisure time physical activity and mortality and defined the upper limit of benefit or harm associated with increased levels of physical activity. Meeting the minimum of the 2008 Physical Activity Guidelines for Americans, by either moderate- or vigorous-intensity activities, was associated with nearly the maximum longevity benefit. The benefit threshold appeared to be at approximately 3 to 5 times the recommended leisure time physical activity minimum with no excess risk at 10 or more times the minimum. (Arem H, Moore SC, Patel A, et al. Leisure time physical activity and mortality: A detailed pooled analysis of the dose-response relationship. JAMA Intern Med 2015;175:959-967) Read more about physical activity and mortality.

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Prostate Cancer

Genetic Risk Variants and Aggressiveness

The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data from 25,674 prostate cancer cases for 36 single nucleotide polymorphisms (SNPs) which at the time had been validated to be associated with risk. The prostate cancer-risk SNP rs2735839 (G) near the KLK3 gene on chromosome 19q13 was associated with aggressive and high-grade disease. (Helfand BT, Roehl KA, Cooper PR, et al. Associations of prostate cancer risk variants with disease aggressiveness: Results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Hum Genet 2015;134:439-450)

Genetic Susceptibility for Aggressiveness

In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, the investigators identified two loci associated with Gleason score, a pathological measure of disease aggressiveness. Both loci (rs35148638 at 5q14.3 and rs78943174 at 3q26.31) are near genes involved in vascular disease, cell migration and metastasis. (Berndt SI, Wang Z, Yeager M, et al. Two susceptibility loci identified for prostate cancer aggressiveness. Nat Commun 2015;6:6889. doi: 10.1038/ncomms7889)

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CT Scanning

EDITORIAL: Berrington de Gonzalez A, Kleinerman RA. CT scanning: Is the contrast material enhancing the radiation dose and cancer risk as well as the image? Radiology 2015; 275:627-629.

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Stomach Cancer


REVIEW: Abnet CC, Corley DA, Freedman ND, Kamangar F. Diet and upper gastrointestinal malignancies. Gastroenterology 2015;148:1234-1243.

Drinking Water Source

Data on 306 cases and 605 controls from the Golestan Gastric Cancer Case-Control Study showed significantly increased risk associated with unpiped and unchlorinated drinking water sources, particularly wells and surface water. (Eichelberger L, Murphy G, Etemadi A, et al. Risk of gastric cancer by water source: Evidence from the Golestan case-control study. PLoS One 2015;10:e0128491)

Genetic Susceptibility

A genome-wide association study of Chinese gastric cancer observed one SNP, rs10074991 in PRKAA1 at 5p13.1, at genome-wide significance for both cardia and non-cardia gastric cancers, while rs2294693 at 6p21.1 showed genome-wide significance for non-cardia gastric cancer only. A novel association with variants in UNC5CL at 6p21.1 was also found. (Hu N, Wang Z, Song X, et al. Genome-wide association study of gastric adenocarcinoma in Asia: A comparison of associations between cardia and non-cardia tumours. Gut 2015; Epub Jun 30)

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