Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, ...often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor.
Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2) enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9.
Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.
Data ...from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.
For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).
Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.
Thyroid cancer incidence has continuously increased for decades and the causes of this increase are still controversial. The objective of this study was to examine if the increased trend is different ...among the different National Cancer Institute (NCI) Race/Ethnicity Groups (REGs) within the NCI surveillance epidemiology and end results database for the United States.
Using recent 13-year surveillance epidemiology and end results data, we described the specific incidence trend of thyroid cancer for the REGs by tumor size, tested the statistical significance of the trend of incidence, and estimated the annual percentage change (APC) and 95% confidence interval. In addition, we compared the difference of 5-year survival rate among the REGs.
Papillary thyroid cancer incidence significantly increased over 13 years from 1992 to 2004 among the five major REGs. The estimated APC was 5.6% (95% confidence interval = 5.1%-6.1%, p < 0.01) for the non-Hispanic whites group, 4.3% (3.0-5.5, p < 0.01) for the Blacks group, 2.8% (1.5-4.2, p < 0.01) for the Hispanic whites group, 1.5% (0.5-2.5, p < 0.01) for the Asians group, and 1.1% (-2.2-4.6, p = 0.477) for the American Indians/Alaska Natives group, respectively. The APCs among the REGs were significantly different (Z = 7.89, p < 0.001). The upward incidence trend could be seen in all small or large tumors as well as in women or in men. The proportion of local staged thyroid cancer increased by 24% in the Blacks group, 14.4% in the Hispanic whites group, 14.3% in the non-Hispanic whites group, and only 4.0% in the Asians group between two periods of 1992-1996 and 2000-2004. Five-year survival rates of patients with papillary tumor were about 95%, but that of anaplastic tumor ranged from 5.6% to 11.4% among REGs.
The time trend of incidence of thyroid cancer is different among the different NCI REGs. Differences in diagnostic scrutiny may explain the differences in the REG-related trend, but this cannot easily explain the relatively small degree of increase in the trend in the Asian and the Indians/Alaska Natives groups nor can it explain the increase in the trend of large tumors that are likely to be discovered by self-palpation by patients.
Over 200 million people worldwide are affected by thyroid proliferative diseases, including cancer, adenoma, and goiter, annually. The incidences of thyroid malignancies are three to four times ...higher in women, suggesting the possible involvement of estrogen. Based on this observed sex bias, we hypothesize that estrogen modulates the growth and metastatic propensity of thyroid cancer cells.
In this study, two thyroid cell lines (Nthy-ori 3-1 and BCPAP) were evaluated for the presence of estrogen receptor (ER) by Western blot analysis and estrogen responsiveness by using a cell proliferation assay. In addition, the effect of estradiol (E(2)) on modulation of metastatic phenotype was determined by using in vitro adhesion, migration, and invasion assays.
Thyroid cells expressed a functionally active ER-alpha and ER-beta as evidenced by 50-150% enhancement of proliferation in the presence of E(2). E(2) also enhanced adhesion, migration, and invasion of thyroid cells in an in vitro experimental model system that, based on our results, is modulated by beta-catenin.
Our data provide evidence that the higher incidence of thyroid cancer in women is potentially attributed to the presence of a functional ER that participates in cellular processes contributing to enhanced mitogenic, migratory, and invasive properties of thyroid cells. These findings will enable and foster the possible development of antiestrogenic therapy targeting invasion and migration, thus affecting metastatic propensity.
Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 ...US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.
Objectives/Hypothesis:
To examine demographic, histologic, and survival trends of oral cavity and oropharyngeal (OC/OP) squamous cell carcinoma (SCCA) patients over the past 3 decades. To test the ...hypothesis that decreased histologic differentiation and increased disease‐specific survival is related to a decline in smoking rates and an increased percentage of human papillomavirus (HPV)‐related tumors.
Study Design:
Retrospective cohort analysis was done using the Surveillance, Epidemiology, and End‐Results (SEER) database of the national cancer institute.
Methods:
SEER data were used to design seven cohorts: 1975–1979, 1980–1984, 1985–1989, 1990–1994, 1995–1999, 2000–2004, and 2005–2006. Incidence rates, histologic tumor grade. and 5‐year survival rates were analyzed over time. Further subgroup analysis was performed according to subsite, age, gender, and stage.
Results:
In both OC and OP, well‐differentiated (grade I) tumors decreased significantly over time, from 33% to 16% between 1975 and 2006 (P < .001). In contrast, poorly differentiated tumors (grade III) significantly increased from 23% to 34% (P < .001). Over time, 5‐year survival rates of less differentiated tumors improved 57%, whereas survival of well‐differentiated tumors improved only 15.5%. Tonsil, posterior oropharynx and tongue subsites showed the greatest improvement in survival over time.
Conclusions:
Comprehensive population‐based analysis of oral cavity and oropharyngeal carcinoma from 1975 to 2006 demonstrated significant trends toward decreased tumor differentiation and increased survival over time. These findings support the influence of HPV in OC/OP carcinoma and may have implications for treatment, prognosis, and possibly prevention. Laryngoscope, 2010
There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, ...with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual‐level data from ten case–control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43–4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4–20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34‐3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41‐20.8%). Our project of a large pool of case–control studies supports a protective effect of total folate intake on OPC risk.
What's new?
Folate is essential to DNA synthesis and repair, suggesting that folate deficiency, in disrupting normal DNA processes, may facilitate the development of certain cancers, including oral and pharyngeal cancer (OPC). The relationship between folate intake and risk of OPC, however, is unclear. In this analysis of data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, high levels of folate intake were found to be inversely associated with overall OPC risk. The association was strongest for cancer of the oral cavity. Risk of OPC was highest among heavy alcohol drinkers with low folate levels.
The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual‐level pooled data from ten case‐control studies (5959 cases and 12,248 controls) ...participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non‐alcohol energy‐adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40–0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54–0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large‐scale pooled analysis suggest that, although in the presence of between‐study heterogeneity, a greater intake of fiber may lower HNC risk.
What's new?
Higher intake of fruit and vegetables is thought to lower the risk of HNCs. These foods are rich in phytochemicals and vitamins, but could dietary fiber also play a role in this protective effect? In this analysis, the authors pooled data from 10 separate studies to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Their results suggest that a greater intake of fiber may indeed lower HNC risk.
Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective ...mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual‐level pooled data from ten case‐control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study‐specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non‐alcohol energy‐adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45–0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR = 0.52, 95% CI: 0.40–0.68, p for trend = 0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations.
What's new?
A diet rich in fruits and vegetables is thought to offer protection against head and neck cancers (HNC). However, it has not been clear which specific nutrients might play a role in this effect. In this re‐analysis of several previous studies, the authors found that a higher intake of vitamin C from natural sources was associated with a significantly lower risk of anatomical subsites of HNC.
High dietary glycaemic index (GI) and glycaemic load (GL) may increase cancer risk. However, limited information was available on GI and/or GL and head and neck cancer (HNC) risk. We conducted a ...pooled analysis on 8 case-control studies (4081 HNC cases; 7407 controls) from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of HNC, and its subsites, from fixed- or mixed-effects logistic models including centre-specific quartiles of GI or GL. GI, but not GL, had a weak positive association with HNC (OR
= 1.16; 95% CI = 1.02-1.31). In subsites, we found a positive association between GI and laryngeal cancer (OR
= 1.60; 95% CI = 1.30-1.96) and an inverse association between GL and oropharyngeal cancer (OR
= 0.78; 95% CI = 0.63-0.97). This pooled analysis indicates a modest positive association between GI and HNC, mainly driven by laryngeal cancer.
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