A comprehensive study of CD44 rs 187115 variant and cancer risk in a central Chinese population

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction-restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta-analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population.     

Irisin immunohistochemistry in gastrointestinal system cancers

Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.     

Sedentary work and the risks of colon and rectal cancer by anatomical sub-site in the Canadian census health and environment cohort (CanCHEC)

BackgroundSedentary behaviour is a potential risk factor for colorectal cancer. We examined the association between sedentary work, based on body position, and colorectal cancer risk in Canadians.MethodsA working body position category (a. sitting; b. standing and walking; c. sitting, standing, and walking; d. other) was assigned to occupations reported by 1991 Canadian Census respondents based on national occupational counselling guidelines. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for cancers of the colon (overall, proximal, and distal) and rectum in men and women newly diagnosed from 1992 to 2010.ResultsCompared to “sitting” jobs, men in occupations with “other” (non-sitting, −standing, or −walking) body positions had a weakly significant reduced colon cancer risk (HR = 0.93, 95% CI: 0.89, 0.98) primarily attributed to protection at the distal site (HR = 0.90, 95% CI: 0.84, 0.97). Men in “standing and walking” and “sitting, standing, and walking” jobs did not have significantly reduced colon cancer risks. No effects were observed for rectal cancer in men or colon and rectal cancer in women.ConclusionThe two significant findings of this analysis should be followed-up in further investigations with additional information on potential confounders. Null findings for rectal cancer were consistent with other studies.     

Plasma netrin-1 is a diagnostic biomarker of human cancers

Context:?The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues.

Objectives:?To determine whether plasma netrin-1 can be used as a diagnostic biomarker of human cancer.

Materials and Methods:?A total of 300 cancer plasma samples from breast, renal, prostate, liver, meningioma, pituitary adenoma, glioblastoma, lung, pancreatic and colon cancer patients were compared against 138 control plasma samples. Netrin-1 levels were quantified by ELISA and immunohistochemistry.

Results:?Plasma netrin-1 levels were significantly increased in breast, renal, prostate, liver, meningioma, pituitary adenoma, and glioblastoma cancers as compared to control samples.

Discussion and Conclusion:?Our results suggest that plasma netrin-1 can be used as a diagnostic biomarker for many human cancers.     

Multiple primary cancers in Connecticut, 1935-82

Recently, the National Cancer Institute published a comprehensive monograph on multiple primary cancers in Connecticut and Denmark. This paper summarizes some of the observations made on the Connecticut population. Data compiled by the Connecticut Tumor Registry have extended our knowledge about the patterns of multiple primary cancers, especially among long-term survivors of cancer and among patients with relatively rare tumors about which little information currently exists. When compared with the general Connecticut population, cancer patients had a 31 percent (RR = 1.31) increased risk of developing a second cancer and a 23 percent (RR = 1.23) elevated risk of second cancer at a different site from the first. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to develop new cancers in the same or contiguous tissue throughout their lifetimes. Cancers of the colon, uterine corpus, breast, and ovary frequently occurred together, suggesting underlying hormonal or dietary influences. Only patients with prostate cancer were at significantly low risk for second cancer development; this might be an artifact of case finding, since advanced age at initial diagnosis was generally associated with an underascertainment of second cancers. Radiotherapy may have caused rectal and other cancer among patients with cancers of the female genital tract, and leukemia among patients with uterine corpus cancer. Chemotherapy with alkylating agents probably contributed to the excess of acute nonlymphocytic leukemia following multiple myeloma or cancers of the breast and ovary. Genetic susceptibility seemed to explain some tumor complexes, such as the multiple occurrences of cutaneous melanoma and the excess of bone cancer following retinoblastoma. Research into multiple cancer syndromes should enhance our understanding of carcinogenic factors and mechanisms and the development of strategies for cancer prevention and control.     

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

Background

Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC.

Methods and Findings

In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses'' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years).

Conclusion

This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women. Please see later in the article for the Editors'' Summary     

Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori

Background and Aims: The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers. Methods: The subjects were 18 early‐stage gastric cancer specimens resected from 17 patients who had received successful eradication of H. pylori from February 1995 to March 2009. The control group consisted of 36 specimens from noneradicated patients with persistent H. pylori infection who were matched with the subjects in age, sex, and depth of invasion. Clinicopathological features and mucin phenotypes of gastric cancer were clinically and immunohistologically evaluated. Results: The average diameter of gastric cancer was smaller and Ki‐67 index was lower in the eradication group. The morphological distribution of depression types was significantly lower in the control group. Immunohistochemical phenotyping revealed that 72.2% of the lesions in the eradicated group were complete gastric type or gastric predominant mixed type, whereas the percentages of gastric type and intestinal type in the control group were similar. Conclusion: Our findings indicate that the clinicopathological characteristics of gastric cancers detected after H. pylori eradication are different from those of gastric cancers in patients with persistent H. pylori infection. H. pylori eradication may suppress intestinalization during the development of gastric cancer.     

Reduced incidence of skin cancer in patients with alopecia areata: A retrospective cohort study

The risk of skin cancer in patients with alopecia areata (AA) is unknown. While the risk of skin cancer in chronic inflammatory alopecias may be elevated, AA shares many characteristics with vitiligo, an autoimmune illness associated with decreased risk of melanoma and non-melanoma skin cancers. In this retrospective cohort study, we determined the risk of developing skin cancer among patients with AA in a validated cohort relative to matched controls at two tertiary care hospitals in Massachusetts. There was a significantly decreased risk of NMSC in AA patients than controls (OR = 0.63, 95% CI = 0.48–0.81). There was a trend towards a protective effect of AA associated with melanoma (OR = 0.65, 95% CI = 0.39–1.09). There was no difference in anatomic distribution of skin cancer between patients with AA and controls. Our study demonstrates a decreased risk of nonmelanoma skin cancer and a trend towards reduced risk of melanoma in patients with AA.     

Nitrates in drinking water and cancers of the colon and rectum: a meta-analysis of epidemiological studies

Backgroundsome recent studies have suggested that the risks of colon and rectal cancer increase with exposure to higher concentrations of nitrates in drinking water. This study is a meta-analysis of relevant studies.Methodsliterature published up to June 2021 was accessed and final results abstracted. Two cohort studies and seven case-control studies were analysed, and one case-control study not used because of limited data. Mixed effects meta-regression analysis was used to assess trends in colon cancer, rectal cancer, and colon cancer considered together, with nitrate concentrations in drinking water.ResultsThe usually accepted exposure upper limit for nitrates is 11.3 mg/l NO₃-N. However most studies assess a lower range, with only one study providing data over 8 mg/l. Colorectal cancer risk increased by 2.4% (95% limits 0.4–4.5%) per unit increase in nitrate concentration, over a range from very low values to mid-range values. Extrapolation to higher dosages has insufficient data. The trend for rectal cancer is less than that for colon cancer.ConclusionThe increase in colorectal cancer risk with increasing nitrate concentration is lower than in some recent studies, and applies only over a small range. Extrapolation of these results to higher nitrate levels is not warranted. The studies vary greatly in their design, the nitrate concentrations assessed, and in their results. This association is weak and inconsistent, and may be influenced by bias and confounding factors. Any association of drinking water nitrates with colorectal cancer risk is small, and is uncertain.     

Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies

ObjectiveThe purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV) derived from population-based cohort studies by means of meta-analysis.MethodsRelevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers.ResultsSix studies (n = 2,578) were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC), four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37–2.21), with moderate heterogeneity among these studies (I² = 65.8%, P = 0.012). In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47–7.73), 4.89 (95%CI = 2.93–8.16) and 3.84 (95%CI = 2.72–5.42) respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66–6.85), prostate cancer (SIR = 1.45, 95%CI = 0.87–2.42), colon cancer (SIR = 1.26, 95%CI = 0.70–2.27), and breast cancer (SIR = 0.95, 95%CI = 0.50–1.79). Among these site-specific cancers, only NMSC showed moderate heterogeneity (I² = 55.8%, P = 0.06). No publication bias was found by using the Begg’s test and Egger''s test.ConclusionsThis meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC) are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant association between AASV and kidney cancer, prostate cancer, colon cancer and breast cancer. These findings emphasize monitoring and preventative management in AASV patients after cessation of CYC therapy is momentous.     

Site-specific risk factors for colorectal cancer in a Korean population

We investigated the association of colorectal cancer risk factors with different colorectal cancer subsites to assess etiological differences for cancers of the proximal colon, distal colon, and rectum. Included in this study were 869,725 men and 395,501 women who participated in a health examination provided by the Korean National Health System between 1996 and 1997. During up to 7 years of follow-up, 4,144 incident colorectal cancer cases were detected (3,051 men and 1,093 women). Greater height was associated with elevated risk for distal colon cancer and rectal cancer in both men and women. Family history of cancer was associated with higher risk for cancers of the proximal colon in men and distal colon in both men and women. Frequent alcohol consumption and consuming high amounts of alcohol were associated with elevated risk for distal colon cancer in men and higher risk for rectal cancer in women. Frequent meat consumption was associated with risk for proximal colon cancer in men and for rectal cancer in women. Our findings suggest that risk factors for colorectal cancer are different by subsites of colon and rectum, as well as by sex.     

Analysis of a two-stage case-control study with cluster sampling of controls: application to nonmelanoma skin cancer

We present a pseudolikelihood approach for analyzing a two-stage population-based case-control study with cluster sampling of controls. These methods were developed to analyze data from a study of nonmelanoma skin cancer (NMSC). This study was designed to evaluate the role of ultraviolet radiation (UVB) on NMSC risk while adjusting for age group, which is known for all subjects, and for other individual-level factors, such as susceptibility to sunburn, which are known only for participants in the case-control study. The methods presented yield estimates of relative and absolute risk, with standard errors, while accounting naturally for the two-stage sampling of the cohort and cluster sampling of controls.     

Colorectal cancer metastatic disease progression in Australia: A population-based analysis

BackgroundNo previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.MethodsAll localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000–2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.ResultsAfter a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79 years vs <60 years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.ConclusionsAn understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients.     

Association between alcohol consumption and cancers in the Chinese population--a systematic review and meta-analysis

Background

Alcohol consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population.

Methods

Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P<.01 was considered statistically significant.

Results

Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47–2.17) EC, 1.40 (99% CI, 1.19–1.64) gastric cancer, 1.56 (99% CI, 1.16–2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00–1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20–2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60–0.97) and 0.70 (99% CI, 0.49–1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma. Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not significantly associated with lung cancer.

Conclusions

Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the interaction between alcohol consumption and other risk factors for cancers in Chinese and other populations.