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Discovering the causes of cancer and the means of prevention

Scientific Highlights

Recently Published DCEG Papers

July 2013 - Linkage Newsletter

Topics

All Cancers

Cancer and Amyotrophic Lateral Sclerosis

Investigators linked data from 16 population-based cancer registries of the NCI SEER (Surveillance, Epidemiology, and End Results) Program to death certificates and observed elevated mortality from amyotrophic lateral sclerosis among survivors of melanoma and tongue cancer, and reduced mortality among prostate cancer survivors. (Freedman DM, Curtis RE, Daugherty SE, et al. The association between cancer and amyotrophic lateral sclerosis. Cancer Causes Control 2013;24:55–60)

Diabetes, Obesity, and Cancer Incidence

Self-reported diabetes confers additional risk, beyond that of being overweight or obese, for cancer overall, excluding prostate, and for certain sites, including the bladder, colon, endometrium, kidney, liver, pancreas, rectum, and stomach. (Lai GY, Park Y, Hartge P, et al. The association between self-reported diabetes and cancer incidence in the NIH-AARP Diet and Health Study. J Clin Endocrinol Metab 2013;98:E497–E502)

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All-Cause Mortality

Trends in Smoking-related Mortality

Over the past 50 years, the risk of death from cigarette smoking has continued to increase among women, with increased risks now nearly identical for men and women, while risks for men have plateaued at the high levels seen in the 1980s, except for a continuing, unexplained increase in mortality from chronic obstructive pulmonary disease. (Thun MJ, Carter BD, Feskanich D, et al. 50-year trends in smoking-related mortality in the United States. N Engl J Med 2013;368:351–364)

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Bladder Cancer

Smoking, Genetic Factors, and Bladder Cancer

Testing for interactions between smoking and 12 bladder cancer susceptibility loci, individually and combined, demonstrated that the potential effect of eliminating smoking on the number of bladder cancer cases is greater for individuals at higher genetic risk. (Garcia-Closas M, Rothman N, Figueroa JD, et al. Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer. Cancer Res 2013;73:2211–2220)

Vitamin D and Bladder Cancer

Increased risk of bladder cancer was observed among persons with low plasma levels of 25-hydroxyvitamin D(3), particularly among persons with muscle-invasive tumors and low expression of FGFR3, markers of more aggressive bladder cancer. (Amaral AF, Méndez-Pertuz M, Muñoz A, et al. Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: A mechanism-based epidemiological study. J Natl Cancer Inst 2012;104:1897–1904)

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Breast Cancer

Circulating Carotenoids and Risk of Breast Cancer

In a pooled analysis of eight cohort studies with prospective data on plasma or serum carotenoids, women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids were at reduced risk of breast cancer. (Eliassen AH, Hendrickson SJ, Brinton LA, et al. Circulating carotenoids and risk of breast cancer: Pooled analysis of eight prospective studies. J Natl Cancer Inst 2012;104:1905–1916)

New Genetic Loci Associated with Breast Cancer Risk

Approximately 30,000 single nucleotide polymorphisms (SNPs) were genotyped in 45,000 breast cancer cases and 42,000 controls in the Breast Cancer Association Consortium, identifying SNPs at 41 new breast cancer susceptibility loci at genome-wide significance, adding to the 27 identified previously. (Michailidou K, Hall P, Gonzalez-Neira A, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 2013;45:353–361)

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Cervical Cancer

Cervical Cancer Screening Guidelines

Evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests and cancer precursors were developed based on literature review and data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan, resulting in recommendations for similar management of women with similar risks. (Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013;17:S1–S27) (For more information about the guidelines and eight associated reports, see the article “Cervical Cancer Screening and Clinical Management in the HPV Era” in this issue of Linkage.)

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Endometrial Cancer

Body Mass Index, Physical Activity, and Endometrial Cancer Survival

Higher prediagnosis body mass index increased the risk of 5- and 10-year overall and disease-specific mortality among women diagnosed with endometrial cancer, whereas physical activity lowered the risk in the NIH-AARP Diet and Health Study. (Arem H, Park Y, Pelser C, Ballard-Barbash R, et al. Prediagnosis body mass index, physical activity, and mortality in endometrial cancer patients. J Natl Cancer Inst 2013;105:342–349)

Etiology of Uterine Sarcomas

In the largest etiological study of uterine sarcomas to date, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for endometrioid endometrial carcinomas. (Felix AS, Cook LS, Gaudet MM, et al. The etiology of uterine sarcomas: A pooled analysis of the Epidemiology of Endometrial Cancer Consortium. Br J Cancer 2013;108:727–734)

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Menopausal Hormone Therapy and Endometrial Cancer
(See under Hormones)


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Genetics

Discovery of RTEL1 Mutations in Dyskeratosis Congenita

Using exome sequencing, the authors identified mutations in RTEL1, a helicase with critical telomeric functions, in two families with Hoyeraal Hreidarsson syndrome. This syndrome is a clinically severe variant of dyskeratosis congenita, an inherited bone marrow failure and cancer predisposition syndrome. (Ballew BJ, Yeager M, Jacobs K, et al. Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita. Hum Genet 2013;132:473–480)

9p21.3 Region and Risk of Cancer

Common genetic variants in cyclin-dependent kinase inhibitors 2A (CDKN2A), and possibly nearby genes, were associated with esophageal squamous cell carcinoma, endometrial cancer, colorectal cancer, colorectal adenoma, and osteosarcoma, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis. (Gu F, Pfeiffer RM, Bhattacharjee S, et al. Common genetic variants in the 9p21 region and their associations with multiple tumours. Br J Cancer 2013;108:1378–1386)

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Hormones

Diethylstilbestrol and Common Adult Medical Conditions

Prenatal exposure to diethylstilbestrol was found to be associated with several common medical conditions in adulthood, including diabetes, all cardiovascular disease, coronary artery disease, myocardial infarction, high cholesterol, hypertension, osteoporosis, and fractures. (Troisi R, Hyer M, Hatch EE, et al. Medical conditions among adult offspring prenatally exposed to diethylstilbestrol. Epidemiology 2013;24:430–438)

In Vitro Fertilization and Cancer Risk

In a record linkage study from a health maintenance organization in Israel, women evaluated and/or treated for infertility with in vitro fertilization had no significantly increased risks of breast, endometrial, or ovarian cancer. (Brinton LA, Trabert B, Shalev V, et al. In vitro fertilization and risk of breast and gynecologic cancers: A retrospective cohort study within the Israeli Maccabi Healthcare Services. Fertil Steril 2013;99:1189–1196)

Menopausal Hormone Therapy and Endometrial Cancer

Data from the NIH-AARP Diet and Health Study show that long duration of estrogen plus progestin use increased endometrial cancer risk, specifically long durations of sequential progestins, particularly among thin-to-normal weight women, whereas decreased endometrial cancer risk was observed for users of short-duration continuous progestins. (Trabert B, Wentzensen N, Yang HP, et al. Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk? Int J Cancer 2013;132:417–426)

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Liver Cancer

Glycation End Products and Liver Cancer

Prediagnostic serum concentrations of the soluble receptor for advanced glycation end products were found to be inversely associated with liver cancer among male smokers. (Moy KA, Jiao L, Freedman ND, et al. Soluble receptor for advanced glycation end products and risk of liver cancer. Hepatology 2013; Jan 16 [E-pub ahead of print])

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Lung Cancer

Sex Differences in Smoking-related Lung Cancer Risk

The EAGLE (Environment And Genetics in Lung cancer Etiology) study found the slope of odds ratios for pack-years was steeper among men than among women, which does not support a higher female susceptibility to tobacco-related lung cancer. (De Matteis S, Consonni D, Pesatori AC, et al. Are women who smoke at higher risk for lung cancer than men who smoke? Am J Epidemiol 2013;177:601–612)

Telomere Length, TERT, and Lung Cancer

A nested case-control study of lung cancer among mostly never-smoking women in China showed a dose-response relationship between lymphocyte telomere length and risk of lung cancer and the rs2736100 G allele in the TERT-CLPTM1L locus on chromosome 5p15.33. (Lan Q, Cawthon R, Gao Y, et al. Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China. PLoS One 2013;8:e59230. E-pub 2013 Mar 26)

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Lymphoma

Burkitt Lymphoma Among Transplant Recipients

Solid organ transplant recipients were found to have a 23-fold greater incidence of Burkitt lymphoma than the general population, with risk peaking 3–8 years after the time of transplantation and generally associated with Epstein-Barr virus-seropositivity. (Mbulaiteye SM, Clarke CA, Morton LM, et al. Burkitt lymphoma risk in U.S. solid organ transplant recipients. Am J Hematol 2013;88:245–250)

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Methods

Risk Prediction Based on Polygenic Models

The authors report a new method to estimate the predictive performance of polygenic models for risk prediction and assess predictive performance for 10 complex traits or common diseases. (Chatterjee N, Wheeler B, Sampson J, et al. Projecting the performance of risk prediction based on polygenic analyses of genome-wide association studies. Nat Genet 2013;45:400–405)

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Occupational Cancer

Formaldehyde and Decreased Lymphocytes

Formaldehyde-exposed workers, previously found to have decreased total lymphocyte counts, had decreased counts of natural killer cells, regulatory T cells, and CD8(+) effector memory T cells, which may shed light on the possible mechanism of action of this human carcinogen. (Hosgood HD 3rd, Zhang L, Tang X, et al. Occupational exposure to formaldehyde and alterations in lymphocyte subsets. Am J Ind Med 2013;56:252–257)

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Pancreatic Cancer

Fine-mapping Common Pancreatic Cancer Susceptibility Regions

The authors characterized germline variation in three genomic regions on chromosomes 1q32.1, 5p15.33, and 13q22.1 associated with pancreatic cancer risk in genome-wide association studies (GWAS) and showed that targeted resequencing leads to the discovery of novel variants and improves the completeness of germline sequence variants for fine-mapping GWAS susceptibility loci. (Parikh H, Jia J, Zhang X, et al. A resequence analysis of genomic loci on chromosomes 1q32.1, 5p15.33, and 13q22.1 associated with pancreatic cancer risk. Pancreas 2013;42:209–215)

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Prostate Cancer

Prostate Cancer and Pesticide Use

Using data from the Agricultural Health Study, the authors found that organophosphate insecticides fonofos, malathion, and terbufos and the organochlorine insecticide aldrin were significantly associated with risk of aggressive prostate cancer. (Koutros S, Beane Freeman LE, Lubin JH, et al. Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study. Am J Epidemiol 2013;177:59–74)

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Renal Cancer

Adipocyte-secreted Hormones and Renal Cell Carcinoma

Elevated levels of circulating adiponectin, an adipocyte-secreted peptide hormone, are associated with decreased subsequent risk of renal cell carcinoma, with low levels appearing to mediate the association between obesity and renal cell carcinoma. (Liao LM, Weinstein SJ, Pollak M, et al. Prediagnostic circulating adipokine concentrations and risk of renal cell carcinoma in male smokers. Carcinogenesis 2013;34:109–112)

Genetic Susceptibility and Renal Cancer

Through a new genome-wide association study (GWAS) and a meta-analysis with published GWAS, a novel susceptibility locus for renal cancer was mapped to 2q22.3 marked by rs12105918, with the signal localizing to intron 2 of the ZEB2 gene (zinc finger E box-binding homeobox 2). (Henrion M, Frampton M, Scelo G, et al. Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer. Hum Mol Genet 2013;22:825–831)

Racial Differences in the Role of Chronic Renal Failure in Renal Cell Carcinoma

Chronic renal failure was associated with a 4.7-fold increased risk of renal cell carcinoma overall, with greater risks observed among blacks (8.7-fold) than whites (2.0-fold) and among subjects without a history of diabetes (8.3-fold) than subjects with diabetes (1.9-fold). (Hofmann JN, Schwartz K, Chow WH, et al. The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans. Cancer Causes Control 2013;24:167–174)

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Thyroid Cancer

Risk of Thyroid Cancer Among Childhood Cancer Survivors

To assist with long-term clinical monitoring of childhood cancer survivors, the authors developed three absolute risk models for second primary thyroid cancer based on demographic data, radiation and chemotherapy treatment information, and other medical records data from the Childhood Cancer Survivor Study (CCSS), the Nordic CCSS, and the Late Effects Study Group. (Kovalchik SA, Ronckers CM, Veiga LH, et al. Absolute risk prediction of second primary thyroid cancer among 5-year survivors of childhood cancer. J Clin Oncol 2013;31:119–127)

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Back to the July 2013 issue of Linkage