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Discovering the causes of cancer and the means of prevention

Scientific Highlights November 2017 - February 2018

Posted on February 02, 2018

Updated April 5, 2018

Cancer Topics

All Cancers

Oral Contraceptives

Data on women in the prospective NIH-AARP Diet and Health Study were used in two studies to evaluate the association between oral contraceptive (OC) use and cancer incidence. Any OC use conferred a statistically significant 3% reduction in the risk for any cancer. Expected risk reductions that strengthened with duration of use were identified for ovarian and endometrial cancers and were suggested for kidney cancer. Long-term OC use was consistently associated with reduced ovarian cancer risk across lifestyle factors, while the greatest risk reductions for endometrial cancer were observed among women at risk for chronic diseases (i.e., smokers, obese BMI). Risk was reduced for non-Hodgkin lymphoma (hazard ratio = 0.79) with 10+ years of use. In addition, there was a 37% reduced risk for bladder cancer and 46% increased risk for pancreatic cancer among long-term users who were ≤60 years of age at baseline. (Michels KA, Brinton LA, Pfeiffer RM, Trabert B. Oral contraceptive use and risks of cancer in the NIH-AARP Diet and Health Study. Am J Epidemiol 2018; Epub Jan 31. Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol 2018; Epub Jan 18)

Pregnancy, Perinatal Factors, and Hormones

REVIEW – Troisi R, Bjørge T, Gissler M, et al. The role of pregnancy, perinatal factors, and hormones in maternal cancer risk: A review of the evidence. J Intern Med 2018; Epub Feb 24.

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All-Cause Mortality

Metabolomics

A serum metabolomic analysis of 620 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study revealed the strongest associations with overall mortality for N-acetylvaline), and dimethylglycine, 7-methylguanine, C-glycosyltryptophan, taurocholate, and N-acetyltryptophan. C-Glycosyltryptophan, 7-methylguanine, and 4-androsten-3beta,17beta-diol disulfate were statistically significantly associated with CVD mortality. No metabolite was associated with cancer mortality at false discovery rate <0.1. (Huang J, Weinstein SJ, Moore SC, et al. Serum metabolomic profiling of all-cause mortality: A prospective analysis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study Cohort. Am J Epidemiol 2018; Epub Jan 30).

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Breast

Insulin-Like Growth Factor

Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. In a cross-sectional analysis of healthy women who donated normal breast tissue to the Komen Tissue Bank for research, investigators found evidence of associations of serum levels of IGF-I and IGFBP-3 with histologic measures of TDLU involution. Higher circulating levels of postmenopausal IGFBP-3 were associated with greater degrees of TDLU involution, indicated by lower TDLU count, among both Caucasian and African American women. Among Caucasian women, there were also positive associations of premenopausal IGF-I:IGFBP-3 molar ratio with both TDLU count and the product of TDLU count and acini count/TDLU. (Oh H, Pfeiffer RM, Falk RT, et al. Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 in relation to terminal duct lobular unit involution of the normal breast in Caucasian and African American women: The Susan G. Komen Tissue Bank. Int J Cancer 2018; Epub Feb 22).

Metabolomics and Breast Cancer Risk

A metabolomic study of prediagnostic serum from postmenopausal women was conducted to identify body mass index (BMI)-associated metabolites that were also associated with breast cancer risk. A total of 67 of 617 identified metabolites were associated with BMI and two of these metabolites—16a-hydroxy DHEA 3-sulfate and 3-methylglutarylycarnitine—were strongly associated with breast cancer risk. These metabolites and allo-isoleucine and 2-methylbutyrylcarnitine were also associated with estrogen receptor (ER)+ breast cancer. The addition of these metabolites to models caused the BMI–breast cancer association to attenuate. Taken together, the findings point toward metabolic pathways that may contribute to breast carcinogenesis and that may underlie the association of BMI with increased risk of postmenopausal breast cancer. (Moore SC, Playdon MC, Sampson JN, et al. A metabolomics analysis of body mass index and postmenopausal breast cancer risk. J Natl Cancer Inst 2018; Epub Jan 9)

Microbiome

The diversity and composition of the gut microbiota may affect breast cancer risk by modulating systemic levels of estrogens and inflammation. This hypothesis was tested among 48 postmenopausal breast cancer cases and 40 controls by identifying breast cancer associations with an inflammation marker, estrogen levels, and fecal microbes that were or were not coated with mucosal immunoglobulin A (IgA). Breast cancer was found to be associated with significant, but differing, associations with both the immune-recognized (IgA-positive) and -unrecognized (IgA-negative) gut microbiota. In their IgA-positive microbiota, cases had increased abundance of Immune System Diseases metabolic pathways but low alpha diversity. The cases’ IgA-negative microbiota also had low alpha diversity; however, their IgA-negative microbiota alpha diversity was not correlated with their estrogen levels. These findings suggest that breast cancer risk may be influenced through enterohepatic cycling of estrogens by the IgA-negative microbiota and also through immune-mediated pathways by the IgA-positive microbiota. (Goedert JJ, Hua X, Bielecka A, et al. Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota. Br J Cancer 2018; Epub Jan 23)

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Endometrium

Alcohol and Estrogen Metabolites

Understanding hormonal mechanisms influenced by lifestyle exposures, such as alcohol consumption, may provide targets for cancer prevention in high-risk populations. In this population of 1864 postmenopausal women within the Women’s Health Initiative-Observational Study, there was a positive association between alcohol consumption and estrone, estradiol and 2-hydroxylation estrogen metabolite concentrations among menopausal hormone therapy (MHT) users. There was also an association between liquor consumption and parent estrogens among non-MHT users, who consumed larger doses of liquor than MHT users. The study strengthens the evidence that alcohol consumption increases circulating estrogen among postmenopausal women. (Playdon MC, Coburn SB, Moore SC, et al. Alcohol and oestrogen metabolites in postmenopausal women in the Women's Health Initiative Observational Study. Br J Cancer 2017; Epub Dec 12)

Recurrence by Race and Ethnicity

Non-Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence, compared to non-Hispanic white (NHW) women. Data from the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study extend the literature on racial disparities in EC by demonstrating higher recurrence risk among NHB women diagnosed with low-grade endometrioid, carcinosarcoma or stage I tumors, compared to their NHW counterparts, while Hispanic women with stage III disease experienced higher recurrence risk. No racial differences in recurrence risk for women were observed in subgroups characterized by other tumor characteristics, suggesting some specificity in the association. (Felix AS, Brasky TM, Cohn DE, et al. Endometrial carcinoma recurrence according to race and ethnicity: An NRG Oncology/Gynecologic Oncology Group 210 Study. Int J Cancer 2018; Epub 2017 Nov 26)

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Esophagus

Hot Tea Consumption

EDITORIAL- Kamangar F, Freedman ND. Hot tea and esophageal cancer. Ann Intern Med 2018; Epub Feb 6.

Polycyclic Aromatic Hydrocarbons

Consumption of maté, an infusion of the herb Ilex paraguariensis (yerba maté), is associated with increased risk of esophageal squamous cell carcinoma (ESCC), but the carcinogenic mechanism is unclear. Commercial brands of yerba maté contain high levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are acquired during the traditional drying process. This study characterized exposure to PAHs in the urine of 244 maté drinkers over a wide range of maté consumption. The urinary concentrations of PAH metabolites were significantly associated with self-reported amount of recent maté intake, with concentrations of some PAH metabolites as much as results from smoking cigarettes. The PAH content of maté may contribute to the increased risk of ESCC in maté drinkers. (Lopes AB, Metzdorf M, Metzdorf L, et al. Urinary concentrations of polycyclic aromatic hydrocarbon metabolites in maté drinkers in Rio Grande do Sul, Brazil. Cancer Epidemiol Biomarkers Prev 2017; Epub Dec 20)

Selenium and Other Minerals

Studies conducted in China linked selenium deficiency to higher risk of esophageal squamous cell carcinoma (ESCC), but this has not been widely tested outside that selenium-deficient region. A study of ESCC cases and controls from the Golestan Cohort Study, conducted in Iran, a high-risk area for ESCC, showed relatively high selenium status among the population generally and no evidence of association between selenium or chromium concentrations in toenails and the risk of ESCC. (Hashemian M, Murphy G, Etemadi A, et al. Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study. Cancer Med 2017; Epub Nov 10)

Sex Steroid Hormones

Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. In the first population-based study to evaluate whether sex steroid hormones underlie this sex disparity, higher androgen:estrogen ratio metrics were associated with increased odds of EA. All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. The study provides tentative evidence that androgen:estrogen balance may be a factor related to EA. (Petrick JL, Falk RT, Hyland PL, et al. Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study. PLoS One 2018 Jan 17;)

COMMENTARY – Van Loon K, Mwachiro MM, Abnet CC, et al. The African Esophageal Cancer Consortium: A Call to Action. J Glob Oncol 2018 Jan 25.

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Hematologic Cancers

Magnesium and Epstein-Barr Virus

Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (eBL). EBV control was improved by magnesium (Mg2+) supplementation in XMEN, an X-linked genetic disease associated with Mg2+ deficiency, high circulating EBV levels (viral loads), and EBV-related lymphomas. This study reports the results of an investigation of the relationship between Mg2+ levels and EBV levels and eBL in Uganda. There were strong, consistent, and independent inverse associations between plasma Mg2+ levels and peripheral blood EBV viral load in women, and with eBL risk in children, consistent with the hypothesis. Overall, there was evidence of mild Mg2+ deficiency in about 14% of healthy children, about 35% of women with low EBV viral load, and about 43% of children with eBL. These results suggest that mild Mg2+ deficiency is relatively frequent and may be relevant for EBV control in Uganda. (Juan R, Otim I, Nabalende H, et al. Plasma magnesium is inversely associated with Epstein-Barr virus load in peripheral blood and Burkitt lymphoma in Uganda. Cancer Epidemiol 2018; Epub 2017 Dec 14)

Physical Activity

An investigation of the relationships of physical activity and TV viewing time before and after diagnosis of a hematologic cancer with mortality was conducted among the NIH-AARP Diet and Health. Increased moderate- to vigorous-intensity physical activity (MVPA) both before and after diagnosis was associated with reduced risk of all-cause mortality among adult survivors of non-Hodgkin lymphoma, myeloma, and leukemia. Pre-diagnosis MVPA was also related to decreased risk of hematologic cancer-specific mortality. By comparison, the association between post-diagnosis MVPA and hematologic cancer-specific mortality was not statistically significant. The results for TV viewing and mortality risk did not show a clear pattern. (Schmid D, Behrens G, Arem H, et al. Pre- and post-diagnosis physical activity, television viewing, and mortality among hematologic cancer survivors. PLoS One 2018 Jan 31)

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Human Papillomavirus

Oral HPV Infection

Data from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate the population-level effect of prophylactic human papillomavirus (HPV) vaccination on the burden of oral HPV infections in young U.S. women and men. HPV vaccination was associated with an estimated 88% reduction in prevalence of vaccine-type oral HPV 16/18/6/11 infections among vaccinated young adults in the United States. However, because of a vaccination rate of only 18.3% (29.2% in women and 6.9% in men) between 2011 and 2014 among individuals 18 to 33 years of age, the population-level effect on oral HPV16/18/6/11 infections was a modest 17% overall, and particularly low in men, 6.9%. (Chaturvedi AK, Graubard BI, Broutian T, et al. Effect of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the United States. J Clin Oncol 2018; Epub 2017 Nov 28)

T-cell Receptor Repertoires

It is unknown why a minority of women fail to control human papillomavirus (HPV) cervical infection and go on to develop precancer/cancer. Differences in T-cell receptor (TCR) repertoires may identify HPV 16-infected women at highest risk for progression. In an exploratory case-control study nested within the Guanacaste HPV Natural History Study, using a novel deep-sequencing approach to interrogate the CDR3 β-chain region of the TCR, differences in the TCR repertoires of women who controlled or failed to control their HPV 16 infection were detected. Women who developed HPV 16-associated CIN 3+ (cases) had a more diverse T-cell repertoire (i.e. more unique TCR sequences [TCR richness]) at the time of lesion diagnosis compared to women with an incidentally detected cervical HPV 16 infection that was undetectable within 12 months (controls). Further, the relative abundance of a specific V gene (TRBV6-7) was on average twice as abundant among controls compared to cases. The combination of both TCR richness and V gene usage was strongly predictive of case-control status. (Lang Kuhs KA, Lin SW, Hua X, et al. T-cell receptor repertoire among women who cleared and failed to clear cervical human papillomavirus infection: An exploratory proof-of-principle study. PLoS One 2018 Jan 31)

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Liver

IFNL4 and Hepatitis C Virologic Relapse

Analysis of data from POLARIS-2, a phase III clinical trial of sofosbuvir, velpatasvir, and voxilaprevir for the treatment of chronic infection with hepatitis C virus (HCV), extends previous observations that IFNL4 genotype is associated with virologic relapse. Higher rates of failure with sofosbuvir-based treatment among black patients compared with whites reported in some studies likely reflect a lower frequency of favorable IFNL4 genotypes in that population. In contrast, given that Asians have the highest frequency of favorable IFNL4 genotypes, relapse may be least frequent in Asian populations. Consideration of these relationships might improve global strategies to treat and control HCV infection. (O'Brien TR, Kottilil S, Pfeiffer RM. IFNL4 genotype is associated with virologic relapse after 8-week treatment with sofosbuvir, velpatasvir, and voxilaprevir. Gastroenterology 2017; Epub Nov 3)

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Methods

Detecting Mediators

The authors introduced a new method for testing multiple biomarkers that may mediate exposure/disease relationships. This computationally efficient method can maintain specified family-wise error rates (FWER) and false discovery rates (FDR), and should be very useful in modern studies evaluating high dimensional biomarkers. They applied this new method to a study evaluating the mechanistic relationship between increased BMI and an increased risk of breast cancer. An R package MultiMed is available on https://github.com/SiminaB/MultiMed-devel. (Sampson JN, Boca SM, Moore SC, et al. FWER and FDR control when testing multiple mediators. Bioinformatics 2018; Epub Feb 6)

Integrating Clinical and Omics Data

Investigators used a multi-omic kernel machine learning method to systematically quantify the prognostic values of high-throughput genomic, epigenomic, and transcriptomic profiles individually, integratively, and in combination with clinical factors for 3,382 samples across 14 cancer types. The prognostic performance varied substantially across cancer types. mRNA and miRNA expression profile frequently performed the best, followed by DNA methylation profile. Germline susceptibility variants displayed low prognostic performance consistently across cancer types. The integration of omic profiles with clinical variables can lead to substantially improved prognostic performance over the use of clinical variables alone in half of cancer types examined. Moreover, the kernel machine learning method consistently outperformed existing prognostic signatures, suggesting that including a large number of omic biomarkers may provide substantial improvement in prognostic assessment in the era of precision oncology. (Zhu B, Song N, Shen R, et al. Integrating clinical and multiple omics data for prognostic assessment across human cancers. Sci Rep 2017 Dec 5)

Using Imputed Genotype Data

Genome-wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score-test for genetic association. In this article, through systematic derivation of score-tests, the authors show how imputed data should be handled in a distinct manner in the prospective vs. retrospective likelihoods. Moreover, through an innovative use of one-step maximum-likelihood estimation, they derive a score-test and a corresponding plug-in method for handling imputed genotype in the context of the EB method that cannot be associated with an underlying likelihood. Proposed methods allow valid analysis of imputed SNPs in case-control studies of gene–environment interaction using alternative strategies that have been earlier available only for genotyped SNPs. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package. (Song M, Wheeler W, Caporaso NE, et al. Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies. Genet Epidemiol 2018; Epub 2017 Nov 26)

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Mortality

Drug Overdose

Recent dramatic increases in drug overdose deaths have largely been attributed to opioid-related deaths in non-Hispanic white (NHW) persons, but less attention has been paid to increased rates among other racial and ethnic groups, or the role of drugs other than opioids. Investigators analyzed U.S. overdose deaths among non-Hispanic black (NHB) and Hispanic persons and NHW persons between 2000 and 2015 by drug type. They showed that cocaine-related overdose deaths among NHB persons are on par with heroin- and prescription opioid–related deaths among NHW women and men and that cocaine is a consistent and important contributor to deaths among Hispanic and NHW persons. These deaths are an important, long-term public health problem that is often overlooked. (Shiels MS, Freedman ND, Thomas D, de Gonzalez AB. Trends in U.S. drug overdose deaths in non-Hispanic black, Hispanic, and non-Hispanic white persons, 2000-2015. Ann Intern Med 2017; Epub Dec 5) For more information, read Cocaine contributes to overdose deaths among some minorities in Research News & Highlights.

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Osteosarcoma

Susceptibility Locus Associated with Survival

The investigators conducted a genome-wide association study (GWAS) for overall survival in osteosarcoma using data from a multistage, international collaborative effort. One locus, GLDC/IL33 at 9p24.1, was associated with overall survival, which suggests that germline genetics can influence osteosarcoma outcomes, independent of metastatic disease. The moderate to large effect sizes for a single-nucleotide polymorphism associated with overall survival was similar to the magnitude of effects observed in an earlier GWAS of metastatic disease at osteosarcoma diagnosis. It was also comparable to GWAS of other pediatric and young adulthood cancers, and higher than those observed in adult GWAS of common cancer susceptibility. (Koster R, Panagiotou OA, Wheeler WA, et al. Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients. Int J Cancer 2018; Epub 2017 Dec 23)

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Ovary and Fallopian Tube

Alcohol and Estrogen Metabolites

Understanding hormonal mechanisms influenced by lifestyle exposures, such as alcohol consumption, may provide targets for cancer prevention intervention in high-risk populations. In this population of 1864 postmenopausal women within the Women’s Health Initiative-Observational Study, there was a positive association between alcohol consumption and estrone, estradiol and 2-hydroxylation estrogen metabolite concentrations among menopausal hormone therapy (MHT) users. There was also an association between liquor consumption and parent estrogens among non-MHT users, who consumed larger doses of liquor than MHT users. The study strengthens the evidence that alcohol consumption increases circulating estrogen among postmenopausal women. (Playdon MC, Coburn SB, Moore SC, et al. Alcohol and oestrogen metabolites in postmenopausal women in the Women's Health Initiative Observational Study. Br J Cancer 2017; Epub Dec 12)

Incidence and Survival

Using data from the North American Association of Central Cancer Registries, investigators analyzed population-based incidence and survival data for fallopian tube carcinoma in situ (CIS; a surrogate of serous tubal intraepithelial carcinoma, which may represent the first manifestation of many high-grade cancers that were once considered ovarian primary tumors), tubal carcinomas, and, for comparison, ovarian carcinomas. Reporting of tubal CIS and tubal carcinoma was found to have increased in recent years, likely reflecting changes in pathology processing of specimens and diagnosis. Developing standardized reporting for tubal neoplasms is needed to enable analysis of outcomes for these comparatively uncommon but increasingly recognized tumors. (Trabert B, Coburn SB, Mariani A, et al. Reported incidence and survival of fallopian tube carcinomas: A population-based analysis from the North American Association of Central Cancer Registries. J Natl Cancer Inst 2017; Epub Dec 21)

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Pancreas

Genetic Susceptibility

The largest pancreatic cancer genome-wide association study to date, including 9,040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), identified a novel association at rs78417682 (7p12/TNS3). Replication of 10 promising signals in up to 2,737 patients and 4,752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L), rs2941471 at 8q21.11 (HNF4G), rs4795218 at 17q12 (HNF1B), and rs1517037 at 18q21.32 (GRP). rs78417682 was not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene. (Klein AP, Wolpin BM, Risch HA, et al. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat Commun 2018)

Opium Use

Data from a large-scale prospective cohort of the general population in the Northeast of Iran demonstrated an association of opium consumption with an increased risk of pancreatic cancer in a dose-dependent manner. A significantly higher proportion of patients with pancreatic cancer reported ever use of opium and those who used higher cumulative doses of opium (≥5th quintile) demonstrated a four-times higher risk, which persisted after adjustments for multiple potentially confounding factors, including age, sex, cigarette smoking, alcohol consumption, body mass index, and diabetes mellitus. Opium is now suggested to be an emerging cancer risk factor for pancreatic cancer. (Moossavi S, Mohamadnejad M, Pourshams A, et al. Opium use and risk of pancreatic cancer: A prospective cohort study. Cancer Epidemiol Biomarkers Prev 2017; Epub Dec 20)

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Prostate

Trends in Metastatic Disease

Metastatic prostate cancer remains a highly lethal malignancy in the U.S. As prostate-specific antigen testing declines nationally, investigators used data from the Surveillance, Epidemiology, and End Results registries to perform a detailed assessment of current age- and race-specific incidence trends with quantitative forecasting. The incidence of metastatic prostate cancer was found to have increased more rapidly since 2012, when the United States Preventive Services Task Force recommendations against prostate-specific antigen testing for prostate cancer were issued, resulting in a rise in both future incidence and the number of new cases by 2025. Future incidence rates and the number of new cases were reduced in alternative forecasts based on data prior to 2012 recommendations. The incidence of metastatic disease in black men is still expected to occur at considerably higher rates compared with that in white men. (Kelly SP, Anderson WF, Rosenberg PS, Cook MB. Past, current, and future incidence rates and burden of metastatic prostate cancer in the United States. Eur Urol Focus 2017; Epub Nov 18)

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Skin

Myotonic Dystrophy

Myotonic dystrophy type 1 (DM1) is an inherited multisystem neuromuscular disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene. Recent evidence documents that DM1 patients have an increased risk of certain cancers, but whether skin cancer risks are elevated is unclear. Using the UK Clinical Practice Research Datalink, investigators observed that DM1 patients had a significantly increased risk of skin cancer overall (hazard ratio = 5.44), with the highest risk seen for basal cell carcinoma. (Wang Y, Pfeiffer RM, Alsaggaf R, et al. Risk of skin cancer among patients with myotonic dystrophy type 1 based on primary care physician data from the U.K. Clinical Practice Research Datalink. Int J Cancer 2018; Epub 2017 Nov 20)

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Stomach

Changing Incidence Patterns

The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity. In recent decades, the prevalence rates of these two major causes declined and increased, respectively, with changes in Western lifestyles. Data from 45 North American Association of Central Cancer Tumor Registries indicates that the epidemiology of gastric cancer is changing among non-Hispanic whites, extending prior observations for different population groups. The key finding is an age interaction over time, with rising noncardia incidence among younger persons and falling rates among older persons. These trends are consistent with a birth cohort effect, with rising incidence rates from older to younger generations. Increases were more pronounced among women than men and preferentially involved the corpus of the stomach. If current patterns continue, forecasting models predict two notable reversals by 2030: overall incidence will no longer be decreasing, and female incidence will exceed male incidence rates. (Anderson WF, Rabkin CS, Turner N, et al. The changing face of noncardia gastric cancer incidence among U.S. non-Hispanic Whites. J Natl Cancer Inst 2018; Epub Jan 19). For more information, read “Detailed study of stomach cancer incidence predicts changes in “typical” patient” in Research News & Highlights.

Serum Pepsinogen 1 and anti-Helicobacter pylori

Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori (H. pylori) serology have been used for gastric risk stratification in Asia. This study assessed the utility of these markers in a Western population, male Finnish smokers enrolled in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Pre-diagnostic low SPG1 was associated with increased gastric cancer risk. Even a single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk. (Song M, Camargo MC, Weinstein SJ, et al. Serum pepsinogen 1 and anti-Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males. Aliment Pharmacol Ther 2017; Epub Dec 15)

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Thyroid

Radiation, Gene Mutations, and Fusions

Exposure to ionizing radiation during childhood is a well-established risk factor for thyroid cancer. However, the genetic mechanisms of radiation-associated carcinogenesis remain not fully understood. In this study, targeted next-generation sequencing and RNA-Seq was used to study 65 papillary thyroid cancers (PTCs) from persons exposed to iodine-131 (131I) thyroid as a result of the Chernobyl accident. Driver mutations were identified in 96.9% of these thyroid cancers, including point mutations in 26.2% and gene fusions in 70.8% of cases. Novel driver fusions such as POR-BRAF, as well as STRN-ALK fusions that have not been implicated in radiation-associated cancer before, were found. Relative to tumors with point mutations, the proportion of tumors with gene fusions increased with radiation dose. (Efanov AA, Brenner AV, Bogdanova TI, et al. Investigation of the relationship between radiation dose and gene mutations and fusions in post-Chernobyl thyroid cancer. J Natl Cancer Inst 2017; Epub Nov 18)

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