Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive ...anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin‐fixed paraffin‐embedded samples, HPV DNA detection and genotyping was performed using SPF‐10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16INK4a expression, a cellular surrogate marker for HPV‐associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval CI: 85.1–91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2–99.4%). Among cancers, the highest prevalence was observed in warty–basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16INK4a overexpression was found in 95% of HPV DNA‐positive anal cancers. In view of the results of HPV DNA and high proportion of p16INK4a overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.
What's new?
Human papillomavirus (HPV) is linked to anal cancer through high HPV DNA‐detection rates. Here, in one of the largest international studies to date, HPV DNA was detected in more than 88% of anal cancers and more than 95% of anal intraepithelial neoplasias grades 2/3. HPV16 was the most frequently detected virus type, followed by HPV18. Overexpression of p16INK4a, a surrogate marker for HPV‐associated transformation, was found in 95% of HPV‐positive anal cancers. The data implicate HPV as a causative factor in anal cancer.
Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect ...to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy.
We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10
). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (P
= 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated.
The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.
Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We ...assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003‐2013). Among 55 697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5‐fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N = 48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95% confidence interval CI 1.0‐8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95% CI 0.9‐5.4; N = 89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients.
In this study of 55,697 kidney recipients in the United States, the authors demonstrate a 2.9‐fold elevation in the incidence of bladder cancer following reported treatment for BK polyomavirus nephropathy, suggesting that BK virus may contribute to bladder carcinogenesis.
Treatment trends in head and neck cancer Schlichting, Jennifer A.; Pagedar, Nitin A.; Chioreso, Catherine ...
CCC. Cancer causes & control/CCC, Cancer causes & control,
07/2019, Letnik:
30, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Purpose
Recent advances in head and neck cancer (HNC) treatment, such as increased use of organ-preserving advanced radiation treatments, the approval of cetuximab for HNC treatment, and the increase ...in human papillomavirus (HPV)-related HNC, have changed clinical approaches to HNC management. We sought to identify treatment trends in a population-based cohort of HNC patients.
Methods
The Surveillance, Epidemiology, and End Results Patterns of Care program collected additional treatment and HPV testing information on stratified random samples of HNC patients diagnosed in 1997 (
n
= 473), 2004 (
n
= 1,317), and 2009 (
n
= 1,128). Rao–Scott Chi-square tests were used to examine unadjusted associations between year of diagnosis and patient sociodemographic, tumor, and treatment characteristics. Cochran–Armitage tests for trend were used to examine the hypothesis that certain treatments were used increasingly (or decreasingly) over the time period, while logistic regression was used to examine factors associated with particular treatments.
Results
Use of radiation and chemotherapy without surgery significantly increased for all HNC sites between 1997 and 2009. Cetuximab and taxane use also showed a significantly increasing trend. Lack of insurance was associated with not receiving treatment in multivariate models. The majority (64%) of cases undergoing radiation in 2009 received an advanced treatment, with 55% receiving intensity modulated. The majority of oropharyngeal cases with known HPV status received chemotherapy and radiation only (62%) and nearly all were insured and had one or fewer comorbidities.
Conclusions
Treatment patterns have changed for HNC, leading to increased incorporation of systemic therapy and newer radiation techniques. HPV testing should be targeted for more widespread use, especially in traditionally underserved groups.
Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between ...several pesticides and lung cancer incidence.
We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina.
Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides.
Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (
= 0.049) and borderline for lifetime days (
= 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence.
These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.
Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and can lead to the development of genital warts, and cancers throughout the body. Despite the availability ...of HPV vaccines for over a decade, uptake in the United States among adolescents and young adults remains well below national targets. While most efforts to improve HPV vaccine uptake have rightly focused on adolescents, there is still a tremendous opportunity to improve vaccination among young adults who have not been vaccinated against HPV. To that end, we report an exploratory examination of associations between HPV vaccination status and intentions with psychological traits that may impact HPV vaccine uptake with a national, demographically diverse sample of young adults (N = 1358) who completed an online survey. These psychological traits conceptually mapped onto motivations to: 1) understand health-related information, 2) deliberate, 3) manage uncertainty, and 4) manage threats. We found notable gender differences for the association of these motivations and vaccination status. For women, higher interest in and ability to understand health-related information seemed to distinguish those who reported receiving the HPV vaccine from those who did not. For men, less need to deliberate and greater needs to manage threat and uncertainty seemed to be the distinguishing motives for those who reported receiving the HPV vaccine compared to those who did not. Results for vaccination intentions were less consistent, but there was some evidence to indicate that, regardless of gender, greater health-related information interest and understanding and need to manage uncertainty and threats were associated with increased intention to receive the HPV vaccine, while greater need to deliberate was associated with decreased vaccination intentions. These results suggest that there are psychological differences that are associated with HPV vaccination decisions and that these motivations should be considered in efforts to improve HPV vaccine uptake.
In January 2014, the US government temporarily designated 5F-PB-22, along with three other synthetic cannabinoids (AB-FUBINACA, ADB-PINACA and PB-22), into Schedule I. Over the course of a 4-month ...time period (July–October 2013), our laboratory quantitatively identified 5F-PB-22 in specimens obtained from four postmortem cases. We describe the four cases, to include pertinent autopsy findings and decedent histories, together with quantitative results for 5F-PB-22 determined in postmortem blood and antemortem serum. Samples were prepared via a liquid–liquid extraction at pH 10.2 into hexane : ethyl acetate. Instrumental analysis was achieved with liquid chromatography coupled with electrospray ionization tandem mass spectrometry operating in multiple reaction monitoring mode. Two ion transitions were monitored for the analyte of interest, and one ion transition was monitored for the internal standard. The observed concentration range of 5F-PB-22 is 1.1–1.5 ng/mL for three postmortem blood specimens and one antemortem serum specimen. Three of the decedents experienced abrupt, sudden death; however, one decedent expired after a rapidly deteriorating hospital course.
Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of ...contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population‐based case‐control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08–2.08; p‐trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.
What's new?
Do alcohol and smoking contribute to the risk of developing breast cancer … a second time? Both are risk factors for first breast cancer, and this study set out to identify their impact on contralateral breast cancer risk. The authors set up a case‐control study, where cases had developed cancer in both breasts at different times, and controls had developed cancer in only one breast. They found that alcohol use and smoking after first diagnosis did increase the risk of developing cancer in the second breast, and recommending lifestyle changes could reduce their risk.
Knowledge of mutation processes is central to understanding virtually all evolutionary phenomena and the underlying nature of genetic disorders and cancers. However, the limitations of standard ...molecular mutation detection methods have historically precluded a genome-wide understanding of mutation rates and spectra in the nuclear genomes of multicellular organisms. We applied two high-throughput DNA sequencing technologies to identify and characterize hundreds of spontaneously arising base-substitution mutations in 10 Caenorhabditis elegans mutation-accumulation (MA)-line nuclear genomes. C. elegans mutation rate estimates were similar to previous calculations based on smaller numbers of mutations. Mutations were distributed uniformly within and among chromosomes and were not associated with recombination rate variation in the MA lines, suggesting that intragenomic variation in genetic hitchhiking and/or background selection are primarily responsible for the chromosomal distribution patterns of polymorphic nucleotides in C. elegans natural populations. A strong mutational bias from G/C to A/T nucleotides was detected in the MA lines, implicating oxidative DNA damage as a major endogenous mutagenic force in C. elegans. The observed mutational bias also suggests that the C. elegans nuclear genome cannot be at equilibrium because of mutation alone. Transversions dominate the spectrum of spontaneous mutations observed here, whereas transitions dominate patterns of allegedly neutral polymorphism in natural populations of C. elegans and many other animal species; this observation challenges the assumption that natural patterns of molecular variation in noncoding regions of the nuclear genome accurately reflect underlying mutation processes.
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