Wong-Ho Chow

Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms

BACKGROUND & AIMS Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1 beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. METHODS We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. RESULTS Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o) IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were not associated with any of the cancers studied. CONCLUSIONS A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

Global increases in kidney cancer incidence, 1973-1992

Reports of increasing rates for kidney cancers in several count prompted this analysis of global incidence trends for total kidney cancers and by subsite. International incidence data for 5-year periods 1973–1977, 1978–1982, 1983–1987 and 1988–1992 were obtained from volumes IV to VII of Cancer Incidence in Five Continents published by the International Agency for Research on Cancer. The USA data for the same 5-year periods were obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Percentage changes in incidence rates were computed using the relative difference between the time periods 1973–1977 and 1988–1992, and annual percentage changes in incidence rates were computed using log linear regression. In 1988–1992, kidney cancer incidence rates (age-adjusted to the world-standard population) were highest in France (16.1/100 000 man-years and 7.3/100 000 woman-years) and lowest in India (2.0 and 0.9, respectively). Between 1973–1977 and 1988–1992, incidence rates rose among men and women in all regions and ethnic groups, with a few exceptions, mostly in Scandinavian countries. The largest percentage increase for men was in Japan (171%) and for women in Italy (107%). Rates for renal pelvis cancer were less than 1/100 000 person-years in almost all regions in both sexes, and the temporal trends were inconsistent. Incidence trends for renal parenchyma cancer tracked those for total kidney cancers, and appeared to result from increases in the prevalence of risk factors and in use of diagnostic imaging procedures.

Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977–2005

Background:In the United States, the rates and temporal trends of oesophageal cancer overall and for the two predominant histologic types – adenocarcinoma (ADC) and squamous cell carcinoma (SCC) – differ between Blacks and Whites, but little is known with regard to the patterns among Asians/Pacific Islanders or Hispanics.Methods:Using the Surveillance, Epidemiology, and End Results programme data, we analysed oesophageal cancer incidence patterns by race, sex, and histologic type for the period 1977–2005.Results:Total oesophageal cancer incidence has been increasing among Whites only; the rates among all other race groups have declined. Moreover, rates among White men surpassed those among Blacks in 2004. Oesophageal SCC rates have been decreasing among virtually all racial/ethnic groups; rates among Hispanic and Asian/Pacific Islander men have been intermediate to those of Blacks and Whites, with rates among women being lower than those among Blacks or Whites. The ADC rates among Hispanic men may be rising, akin to the historical trends among Whites and Blacks. The sex ratios for these cancers also varied markedly.Conclusions:These observations may provide clues for aetiological research.

The role of diabetes mellitus in the aetiology of renal cell cancer

Summary To investigate the relation between diabetes mellitus and the risk of renal cell cancer we carried out a population-based retrospective cohort study. Patients identified in the Swedish Inpatient Register who were discharged from hospitals with a diagnosis of diabetes mellitus between 1965 and 1983 formed a cohort of 153 852 patients (80 005 women and 73 847 men). The cohort members were followed up to 1989 by record linkage to three nation-wide registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were computed using age-specific sex-specific and period-specific incidence and mortality rates derived from the entire Swedish population. After exclusion of the first year of observation, a total of 267 incidences of renal cell cancer (ICD-7 : 180.0) occurred in diabetic patients compared with the 182.4 that had been expected. Increased risks were observed in both women (SIR = 1.7, 95 % confidence interval, CI = 1.4–2.0) and men (SIR = 1.3; 95 % CI = 1.1–1.6) throughout the duration of follow-up (1–25 years). A higher risk was seen for kidney cancer (ICD-7 : 180) mortality (SMR = 1.9; 95 % CI = 1.7–2.2, women; SMR 1.7, 95 % CI = 1.4–1.9, men). In comparison with the general population, patients with diabetes mellitus have an increased risk of renal cell cancer. [Diabetologia (1999) 42: 107–112]

The role of interleukin-1 polymorphisms in the pathogenesis of gastric cancer.

This corrects the article DOI: 35006081

The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China

The divergent incidence patterns of gastric cardia and distal stomach cancer may suggest different etiologies. This study examined the role of cigarette smoking, alcohol drinking, and green tea consumption as risk factors for carcinoma by anatomic subsite of stomach.

Identification of New Genetic Risk Variants for Type 2 Diabetes

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r2<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49×10−9 (1.15, 1.10–1.20), 1.45×10−8 (1.13, 1.08–1.18), and 7.14×10−7 (1.13, 1.08–1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.

Dietary habits and stomach cancer in Shanghai, China

Stomach cancer remains the second leading cancer in incidence in Shanghai, China, despite its decline over the past 2 decades. To clarify risk factors for this common malignancy, we conducted a population‐based case‐control study in Shanghai, China. Included in the study were 1,124 stomach cancer patients (age 20–69) newly diagnosed in 1988–1989 and 1,451 controls randomly selected among Shanghai residents. Usual adult dietary intake was assessed using a comprehensive food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Risks of stomach cancer were inversely associated with high consumption of several food groups, including fresh vegetables and fruits, poultry, eggs, plant oil, and some nutrients, such as protein, fat, fiber and antioxidant vitamins. By contrast, risks increased with increasing consumption of dietary carbohydrates, with odds ratios (ORs) of 1.5 (95% confidence interval [CI] 1.1–2.1) and 1.9 (95% CI 1.3–2.9) in the highest quartile of intake among men (p for trend = 0.02) and women (p = 0.0007), respectively. Similar increases in risk were associated with frequent intake of noodles and bread in both men (p = 0.07) and women (p = 0.05) after further adjustment for fiber consumption. In addition, elevated risks were associated with frequent consumption of preserved, salty or fried foods, and hot soup/porridge, and with irregular meals, speed eating and binge eating. No major differences in risk were seen according to subsite (cardia vs. non‐cardia). Our findings add to the evidence that diet plays a major role in stomach cancer risk and suggest the need for further evaluation of risks associated with carbohydrates and starchy foods as well as the mechanisms involved. Int. J. Cancer 76:659–664, 1998. Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

Occupational physical activity and the incidence of cancer of the breast, corpus uteri, and ovary in shanghai

Background. A sedentary life style has been consistently associated with an increased risk of colon cancer, but the evidence for its association with breast and other gynecologic cancers is limited.

The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.