Cancer Risk In Asian Population Research Articles

Abstract P3-01-26: Mammographic density in relation to breast cancer risk factors among Chinese women

Abstract Higher mammographic density (MD) is a known risk factor for breast cancer (BC), however, studies examining determinants of density in Chinese populations are limited. Asian women tend to have higher MD compared to European women, and yet they have a lower overall BC incidence rate. The goal of this study was to investigate the influence of established BC risk factors on quantitatively measured MD among Chinese women. The study population included 7,351 Chinese women, who had mammograms at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, between 2016 and 2017 for different indications, including but not limited to screening exam, breast pain, and suspected breast tumors. Only subjects with BI-RADS (Breast Imaging-Reporting and Data System) diagnostic classification of 1 (negative, n= 2,293), 2 (benign, n= 3,519), and 3 (probably benign, n= 1,539) were included in this analysis. VolparaDensity software was used to obtain quantitative MD measures including absolute dense breast volume and percent breast density. We conducted multivariable linear regression modeling on each density measurement to test for its associations with well-established breast cancer risk factors. The mean age of this study population was 50.1 years old (range= (25, 82)), the average body mass index (BMI) was 24.0 kg/m2 (range= (14.2, 48.9)), and about 46% of women were postmenopausal. The mean absolute dense and percent dense volumes were 58.4 (SD= 32.1) and 14.8 (SD= 7.1, equivalent to Volpara Density Grade= 3), respectively. Associations between quantitative MD measures and BC risk factors did not vary significantly across the three BI-RADS diagnostic classes and we therefore combined these patients in subsequent analyses. Most risk factors we examined showed similar associations with dense volume and percent density. For example, both dense volume and percent density were inversely associated with age, parity, longer duration (> 1 year) of breastfeeding, and postmenopausal status, while they were positively associated with age at menopause. In contrast, the associations with age at menarche and BMI showed opposite directions for dense volume and percent density. While increasing BMI was positively associated with dense volume, it was inversely associated with percent density. Age at menarche, however, was inversely correlated with dense volume, but positively associated with percent density. When stratifying by menopausal status, the associations for age, BMI, and parity were similar among pre- and post-menopausal women, while the associations for age at first birth and breastfeeding were stronger among postmenopausal women. In general, observed breast cancer risk factor associations with quantitative breast density metrics in this Chinese population are similar to those previously reported in Western women. We did not observe striking differences in associations of breast density with reproductive factors and BMI among Asian women in this large analysis based on quantitative density measurements. Other risk factors such as genetic susceptibility loci associated with MD should be examined in large Asian studies to further our understanding on how MD influences breast cancer risk in Asian populations. Citation Format: Hela Koka, Yuan Tian, Deng Lu, Kai Yu, Er-Ni Li, Changyuan Guo, Bin Zhu, Jennifer L Guida, Ariane Chan, Nan Hu, Ning Lu, Gretchen Gierach, Jing Li, Xiaohong R Yang. Mammographic density in relation to breast cancer risk factors among Chinese women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-01-26.

Polygenic risk scores for prediction of breast cancer risk in Asian populations

PurposeNon-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. MethodsThe development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). ResultsThe best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. ConclusionPRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

Quality Diet Index and Risk of Pancreatic Cancer: Findings from the Singapore Chinese Health Study.

Limited research has been conducted on the effect of quality diet index (QDI), which represents a comprehensive assessment of healthy diet quality and quantity, on pancreatic cancer risk in Asian populations. Using data from the Singapore Chinese Health Study, a prospective cohort of 63,257 middle-aged or older Chinese men and women, four QDI scores: the Alternative Health Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the Heathy Diet Indicator (HDI), at baseline were calculated. After 25 years of follow-up, 311 cohort participants developed pancreatic cancer. Cox proportional hazard regression method was used to estimate HR and 95% confidence interval (CI) for pancreatic cancer associated with higher QDI scores. Higher scores of AHEI-2010, aMED, and DASH were significantly associated with lower pancreatic cancer risk (all P trend < 0.05). Compared with the lowest quartile, HRs (95% CIs) of pancreatic cancer for the highest quartiles of AHEI-2010, aMED, and DASH scores were 0.65 (0.46-0.90), 0.57 (0.38-0.85), and 0.66 (0.46-0.95), respectively. These associations were more apparent among men. Overall, there was no statistically significant difference in the QDI-pancreatic cancer risk association between subgroups stratified by levels of body mass index, history of diabetes, and smoking status. Higher QDI scores were significantly associated with reduced risk of pancreatic cancer. The consistent results across multiple QDIs shows that adherence to a healthy diet may lower pancreatic cancer risk, suggesting that dietary modification may be a promising approach for primary prevention of pancreatic cancer.

Abstract 854: Dietary quality indexes and risk of pancreatic cancer: Findings from a prospective cohort study

Abstract Background. Dietary quality index represents a long-term dietary intake of nutritive and non-nutritive compounds. Therefore, it would be more informative for evaluating the association between dietary intake and health outcomes, including pancreatic cancer, in different populations with distinct dietary habits and patterns. Limited research has been conducted on the effect of dietary quality index (DQI) on pancreatic cancer risk in Asian populations. Methods. Using data from Singapore Chinese Health Study, a prospective cohort study of 63,257 Chinese men and women aged 45-74 at enrollment during 1993-1998, we created four diet-quality index scores: the Alternative Health Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI) based on the baseline information collected using validated semi-quantitative food frequency questionnaire. After a mean 17 years of follow-up, 316 participants developed pancreatic cancer. The Cox proportional hazard regression method was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for pancreatic cancer in relation to different levels of these DQI scores. Results. High scores of AHEI-2010, aMED and DASH were associated with lower risk of pancreatic cancer (all Ptrend&amp;lt;0.05). Compared with the lowest quartile, HRs (95% CIs) of pancreatic cancer for the highest quartiles of AHEI-2010, aMED and DASH were 0.65 (0.46-0.90), 0.60 (0.41-0.89), and 0.69 (0.48-0.98), respectively, after adjustment for age, sex, body mass index, alcohol intake, tobacco smoking, and history of diabetes. We did not find a discernable heterogeneity in these dietary quality indexes-pancreatic cancer risk associations by body mass index levels or status of diabetes or smoking. Conclusion. High quality diet is significantly associated with reduced risk of pancreatic cancer. The consistent results across different DQIs support the notion that adherence to a healthy diet may lower the risk of pancreatic cancer, suggesting that dietary modification may be a cost-effective approach for primary prevention of pancreatic cancer. Funding: The Singapore Chinese Health Study was supported by the National Institutes of Health (NIH) of the United States (grants # R01 CA144034 and UM1 CA182876). HN Luu is partially supported by the University of Pittsburgh Medical Center Hillman Cancer Center start-up grant. P Paragomi was supported by the NIH T32CA186873 training grant in cancer epidemiology and prevention; W-P Koh was partially supported by the National Medical Research Council, Singapore (NMRC/CSA/0055/2013). Citation Format: Hung N. Luu, Pedram Paragomi, Aizhen Jin, Renwei Wang, Nithya Neelakantan, Rob M. van Dam, Randall E. Brand, Woon-Puay Koh, Jian-Min Yuan. Dietary quality indexes and risk of pancreatic cancer: Findings from a prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 854.

PARP1 rs1136410 Val762Ala contributes to an increased risk of overall cancer in the East Asian population: a meta-analysis.

ObjectivesTo investigate the association between poly(ADP-ribose) polymerase 1 (PARP1) rs1136410 Val762Ala and cancer risk in Asian populations, as published findings remain controversial.MethodsThe PubMed and EMBASE databases were searched, and references of identified studies and reviews were screened, to find relevant studies. Meta-analyses were performed to evaluate the association between PARP1 rs1136410 Val762Ala and cancer risk, reported as odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 24 studies with 8 926 cases and 15 295 controls were included. Overall, a significant association was found between PARP1 rs1136410 Val762Ala and cancer risk in East Asians (homozygous: OR 1.19, 95% CI 1.06, 1.35; heterozygous: OR 1.10, 95% CI 1.04, 1.17; recessive: OR 1.13, 95% CI 1.02, 1.25; dominant: OR 1.13, 95% CI 1.06, 1.19; and allele comparison: OR 1.09, 95% CI 1.03, 1.15). Stratification analyses by race and cancer type revealed similar results for gastric cancer among the Chinese population.ConclusionThe findings suggest that PARP1 rs1136410 Val762Ala may be significantly associated with an increased cancer risk in Asians, particularly the Chinese population.

Polygenic risk score for genetic evaluation of prostate cancer risk in Asian populations: A narrative review.

Decreasing costs of genetic testing and interest in disease inheritance has changed the landscape of cancer prediction in prostate cancer (PCa), and guidelines now include genetic testing for high-risk groups. Familial and hereditary PCa comprises approximately 20% and 5% of all PCa, respectively. Multifaceted disorders like PCa are caused by a combinatory effect of rare genes of high penetrance and smaller genetic variants of relatively lower effect size. Polygenic risk score (PRS) is a novel tool utilizing PCa-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association study (GWAS) to generate an additive estimate of an individual's lifetime genetic risk for cancer. However, most PRS are developed based on GWAS collected from mainly European populations and do not address ethnic differences in PCa genetics. This review highlights the attempts to generate a PRS tailored to Asian males including data from Korea, China, and Japan, and discuss the clinical implications for prediction of early onset and aggressive PCa.

Methylenetetrahydrofolate reductase gene polymorphisms in the risk of polycystic ovary syndrome and ovarian cancer.

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) in hormone metabolism pathways might cause metabolic disturbances and contribute to the development of polycystic ovary syndrome (PCOS) and ovarian cancer, but the published studies were inconsistent. The aim of the present study was to evaluate the MTHFR C677T (rs1801133) and A1298C (rs1801131) gene polymorphisms in the risk of PCOS and ovarian cancer by meta-analysis. A comprehensive electronic search was conducted in databases for studies published from 1995 to 2020. The pooled ORs were calculated by Revman 5.2 software. Twenty-nine articles including 45 case–control studies were included. We found that MTHFR C677T polymorphisms were correlated with elevated PCOS risk (TT vs. CT+CC: OR = 1.41, 95%CI = 1.20–1.67; TT+CT vs. CC: OR = 1.54, 95%CI = 1.07–2.22; CT vs. CC+TT: OR = 1.18, 95%CI 1.04–1.33; TT vs. CC: OR = 1.47, 95%CI = 1.03–2.11; T vs. C: OR = 1.25, 95%CI = 1.06–1.47), which were more obvious in Middle Eastern subgroup. MTHFR A1298C polymorphisms were also associated with overall PCOS susceptibility (CC vs. AC+AA: OR = 2.55, 95% CI = 1.61–4.03; CC+AC vs. AA: OR = 1.84, 95%CI = 1.04–3.28; CC vs. AA: OR = 2.66, 95%CI = 1.68–4.22; C vs. A: OR = 1.67, 95%CI = 1.03–2.71), which were mainly reflected in Asian subjects. For ovarian cancer, MTHFR C677T polymorphisms were only related with elevated ovarian cancer risk in Asian population, while no significant association was found for A1298C polymorphisms. This meta-analysis suggested that MTHFR C677T and MTHFR A1298C polymorphisms were correlated with elevated PCOS risk. MTHFR C667T only posed a higher risk for ovarian cancer in Asians instead of other populations, while MTHFR A1298C polymorphisms were not related to ovarian cancer risk. Further studies are needed to validate the conclusion.

The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis.

Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.

Association study between CYP24A1 gene polymorphisms and cancer risk

CYP24A1, an essential gene in regulation of vitamin D, has been reported to play an important role in enhancing immune activity and inhibiting tumorigenesis. Previous studies proposed that rs2585428, rs4809960, rs6022999 and rs6068816 in CYP24A1 gene might be greatly associated with cancer risk. To validate the findings, we here investigated the associations of these four polymorphisms and colorectal cancer (CRC) risk in a central Chinese population (426 colon cancer patients, 361 rectal cancer patients and 800 healthy controls). The genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results revealed that the rs4809960 and rs6022999 were strongly associated with the CRC risk, especially with the colon cancer risk. Moreover, the analysis of haplotypes consisting of rs2585428(G > A), rs4809960(T > C), rs6022999(A > G) and rs6068816(C > T) indicated that haplotype ATGC significantly decreased the CRC risk, especially the colon cancer risk. Haplotype GCAT significantly increased the CRC risk, especially the rectal cancer risk. However, haplotype ACAC was only found to be associated with increased risk of CRC. To improve the statistical strength, an updated meta-analysis was further performed. The results showed that rs2585428 was associated with cancer risk in Caucasian population, rs4809960 was associated with breast cancer risk in Caucasian population, and rs6022999 was associated with cancer risk in Asian population. Collectively, the rs4809960 and rs6022999 may be the genetic biomarkers for prediction of colon cancer risk in Chinese population, the rs2585428 and rs6022999 may link to cancer susceptibility in Caucasian population and in Asian population respectly.

Association between the insulin-like growth factor 1 gene rs2195239 and rs2162679 polymorphisms and cancer risk: a meta-analysis

BackgroundMany epidemiological studies have suggested that insulin-like growth factor1 (IGF1) gene single-nucleotide polymorphisms (SNPs) may be associated with cancer risk. Among several commonly studied polymorphisms in IGF1 gene, rs2195239 and rs2162679 attracted many attentions. So we perform a meta-analysis to determine potential associations between IGF1 rs2195239 and rs2162679 polymorphisms and cancer risk.MethodsWe retrieved relevant articles from the PubMed, Embase, and Web of Science databases up to April 30, 2018. Ultimately, thirteen studies were included in the present meta-analysis, which involved 12,515 cases and 19,651 controls. The odd ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the strength of the associations.Resultsrs2195239 reduces the overall cancer risk in homozygote model, as well as reducing cancer risk in Asian populations in allele, homozygote, and recessive models. No significant relationship was found between rs2195239 and breast or pancreatic cancer risk. rs2162679 reduces the overall cancer risk in allele, homozygote, dominant, and recessive models, as well as reducing cancer risk in Asian populations in allele, homozygote, and recessive models.ConclusionsIGF1 rs2195239 and rs2162679 were associated with overall cancer risk based on present studies.

Fine Mapping in Chromosome 3q28 Identified Two Variants Associated with Lung Cancer Risk in Asian Population.

Genome-wide association studies (GWASs) have consistently identified chromosome 3q28 as a lung cancer susceptibility region. To further characterize the potential genetic mechanism of the variants in this region, we conducted a fine-mapping study on chromosome 3q28 region. We performed a target resequencing in 200 lung cancer cases and 300 controls in the screening and followed by validation in multi-ethnic lung cancer GWASs with 12,843 cases and 12,639 controls. For our identified novel variants, we conducted expression quantitative trait loci (eQTL) analysis to reveal the potential target genes. Two susceptibility variants were identified (rs4396880: G>A, OR = 0.35, 95%CI: 0.20-0.62, P = 3.01×10-4; and rs3856776: C>T, OR = 2.05, 95%CI: 1.32-3.18, P = 1.49×10-3) and further supported in Asian population (rs4396880: OR = 0.88, P = 7.43×10-6; and rs3856776: OR =1.17, P = 1.64×10-4). The eQTL analysis showed the A allele of rs4396880 was significantly associated with higher mRNA expression of TP63 (P = 1.70×10-4) in lung tissues, while rs3856776 showed significant association with the expression of LEPREL1-AS1 (P = 6.90×10-3), which was the antisense RNA of LEPREL1 and could suppress the translation of LEPREL1. Notably, LEPREL1 was aberrantly downregulated (P = 2.54×10-18) in lung tumor tissues based on TCGA database. In conclusion, this is the first fine-mapping analysis of 3q28 region in Han Chinese, and we found two variants associated with lung cancer susceptibility in Asian population. What's more, rs3856776 was newly identified and might modulate lung cancer susceptibility by suppressing the function of LEPREL1.

The association between rs16917496 T/C polymorphism of SET8 gene and cancer risk in Asian populations: a meta-analysis.

Epidemiological studies have demonstrated close associations between SET8 rs16917496 T/C polymorphism and cancer risk, but the results of published studies were not consistent. We therefore performed this meta-analysis to explore the associations between rs16917496 T/C polymorphism and cancer risk. Five online databases were searched. Odds ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between rs16917496 T/C polymorphism and cancer risk. In addition, heterogeneity, accumulative, sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 13 publications involving 5878 subjects were identified according to included criteria. No significant cancer risk was observed in genetic model of SET8 rs16917496 T/C polymorphism in Asian populations (C vs. T: OR = 1.04, 95%CI = 0.88–1.23, P = 0.63%; TC vs. TT: OR = 1.17, 95%CI = 0.96–1.24, P = 0.11%; CC vs. TT: OR = 0.90, 95%CI = 0.60–1.37, P = 0.63; TC+CC vs. TT: OR = 1.11, 95%CI = 0.90–1.38, P = 0.33; CC vs. TT+TC: OR = 0.92, 95%CI = 0.65–1.30, P = 0.63). Furthermore, similar associations were found in the subgroup analysis of race diversity, control design, genotyping methods, and different cancer types. In summary, our meta-analysis indicated that the SET8 rs16917496 T/C polymorphism may not play a critical role in cancer development in Asian populations.

Higher serum zinc levels may reduce the risk of cervical cancer in Asian women: A meta-analysis.

ObjectiveThis meta-analysis was conducted to examine the possible association between serum zinc concentration and cervical cancer risk.MethodsPubMed, WanFang, China National Knowledge Infrastructure, and SinoMed databases were searched for relevant articles published between January 1980 and September 2017. Results were combined using a random-effects model, and pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare serum zinc levels in patients with cervical cancer versus controls. Publication bias was evaluated using Begg’s funnel plot and Egger’s regression asymmetry test.ResultsTwelve articles regarding serum zinc levels and cervical cancer were included in this meta-analysis. Combined results showed that serum zinc levels in cervical cancer cases were significantly lower than in controls without cervical cancer (summary SMD –1.379, 95% CI –1.527, –1.231), with high heterogeneity (I2 = 98.8%). Analysis of data stratified by geographic location showed a significant association between serum zinc levels and cervical cancer risk in Asian populations (summary SMD –1.391, 95% CI –1.543, –1.239).ConclusionsHigher serum zinc levels may be a protective factor for cervical cancer in Asian women.

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

BackgroundThe relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations.MethodsThe association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI.ResultsWe confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P=0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P=0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P=0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P=0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P<0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P=0.009).ConclusionTP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

Thyroid disorders and breast cancer risk in Asian population: a nationwide population-based case–control study in Taiwan

ObjectiveTo evaluate whether hyperthyroidism or hypothyroidism increases the risk of subsequent breast cancer in an Asian population.DesignNationwide population-based case–control study.SettingAll healthcare facilities in Taiwan.ParticipantsA total of 103 466 women (mean...

The Interaction of Smoking with Gene Polymorphisms on Four Digestive Cancers: A Systematic Review and Meta-Analysis.

The main purpose of this study was to perform a meta-analysis to assess the interaction between smoking and nine genes (GSTM1, GSTT1, GSTP1, CYP1A1, NAT2, SULT1A1, hOGG1, XRCC1 and p53) on colorectal cancer, gastric cancer, liver cancer and oesophageal cancer. Published articles from the PubMed, ISI and EMBASE databases were retrieved. A total of 67 case-control studies or nested case-control studies were identified for the analysis. The pooled jodds ratio (OR) with 95% confidence interval (CI) was calculated using the random effect model. The overall study showed that the GSTM1 polymorphism was associated with the risk of the four digestive cancers among Asian population (OR 1.284, 95% CI: 1.122-1.470, p: 0). Subgroup analyses by cancer site showed that GSTM1 null genotype increased the gastric cancer risk in total population (OR 1.335, 95% CI: 1.145-1.556, p: 0). However, the association of GSTM1 null genotype with the oesophageal cancer risk was found in smokers (OR 1.382, 95% CI: 1.009-1.894, p:0.044), but not in non-smokers (OR 1.250, 95% CI: 0.826-1.891, p:0.290). Moreover, smokers with the CYP1A1 IIe462Val polymorphism were at an increased cancer risk in Asian population (OR=1.585, 95% CI 1.029-2.442, p: 0.037). None of the other gene-smoking interactions was observed in the above cancers. This meta-analysis reveals two potential gene-smoking interactions, one is between smoking and GSTM1 on oesophageal cancer, and the other is between smoking and CYP1A1 IIe462Val on the four cancers in Asian population. Future studies need to be conducted to verify the conclusions.

Physical activity, sedentary time, and risk of colorectal cancer: the Singapore Chinese Health Study.

Singapore has experienced a marked increase in colorectal cancer incidence over the past 40 years. Evidence from prospective studies in Western Europe and the USA suggests that low physical activity and high amounts of sedentary time are associated with increased colorectal cancer risk. The aim of this study is to evaluate these relationships in an Asian population. The Singapore Chinese Health Study enrolled 63 257 adults between 1993 and 1998. At enrollment, participants reported past year physical activity and time spent sitting. Incident colorectal cancers (n=1994) were identified through 31 December 2014. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. Any strenuous-vigorous or moderate physical activity was reported by 13.7 and 22.1% of the cohort, respectively. Strenuous-vigorous physical activity was associated with statistically significant reduced colorectal cancer risk (HR=0.85; 95% CI: 0.74-0.99 for ≥0.5 h/week vs. none), but moderate was not. In analysis stratified by time spent watching television, an inverse relationship between moderate physical activity and colorectal cancer risk (HR=0.86; 95% CI: 0.72-1.01 for ≥0.5 h/week vs. none) was observed for those who reported at least 3 h/day sitting watching television (Pinteraction=0.042). Participation in strenuous-vigorous physical activity, such as jogging, swimming, or heavy manual labor, was associated with reduced colorectal cancer risk among Singapore Chinese. Further research on physical activity and sedentary behaviors, independently and in combination, and colorectal cancer risk in Asian populations is needed.

ID2020 Rs3803662 significant associated with breast cancer risk in Vietnamese population

Breast cancer is one of the most common malignancies among women worldwide. GWASs have found several potential breast cancer associated SNPs in some populations. Among them, rs13281615, rs889312, rs10941679 and rs3803662 have been found to have strong relationship with breast cancer risk in different populations. Rs3803662 were statisti¬cally significantly associated with breast cancer risk in Asian population, while three others SNPs were showed to have stronger association with breast cancer in American, European and Australian than Asian. In this study, focusing on Vietnamese people only, four these SNPs were investigated to understand more about the association between these variations with breast cancer disease. An optimized genotyping method was used to genotype 600 samples including 300 controls and 300 cases. The result showed that rs13281615, rs889312, and rs10941679 were not associated with Vietnamese breast cancer patients (P&gt;0.05). However, rs3803662 has strong association with breast cancer risk in Vietnamese population (P = 0.00122, OR = 1.454, 95%CI = 1.159-1.826). Allele A plays the role of increasing the risk of breast cancer and the genotype AA shows strongly affecting to increase breast cancer risk. Rs3803662 may involve in the list of markers using for diagnosis breast cancer in Vietnamese people in the future. A further study on larger sample size is certainly required to increase the reliability of the study. We also suggest doing more association studies for other SNPs and analyzing the haplotype to identify multiple breast cancer risk prediction markers for Vietnamese population

Note of clarification of data in the paper entitled "Interferon gamma +874 T/A polymorphism increases the risk of cervical cancer: evidence from a meta-analysis".

We read with great interest the paper entitled "Interferon gamma +874 T/A polymorphism increases the risk of cervical cancer: evidence from a meta-analysis" published online by Sun et al. Their results suggest that interferon gamma ( IFNG) gene +874 T/A polymorphism might contribute to women's susceptibility to cervical cancer. They also found that IFNG +874 T/A polymorphism is associated with increased cervical cancer risk in Asian female population. The result is encouraging. Nevertheless, several key issues are worth noticing. We re-evaluate the association between IFNG +874 T/A polymorphism and cervical cancer risk by performing an updated meta-analysis based on 2777 cases and 2542 controls of 11 studies. We found that IFNG +874 T/A polymorphism was not significantly associated with cervical cancer risk in overall population. We also observed that the polymorphism was associated with enhanced cervical cancer risk in Asian population and was relevant to increased squamous cell cervical cancer risk.

Associations of common IL-4 gene polymorphisms with cancer risk: A meta-analysis.

Cancer incidence is dramatically increasing worldwide, therefore improved prediction and therapeutic methods are needed. Single nucleotide polymorphisms in cytokine genes may contribute to carcinogenesis. Interleukin (IL)-4 gene polymorphisms have been intensively studied with regard to their associations with cancer. However, the results of these previous studies remain inconclusive. The present study, therefore, aimed to conduct a meta-analysis of previously published studies in order to clarify the association of IL-4 with cancer risk. Eligible published articles were searched in Medline, PubMed, Embase and China National Knowledge Infrastructure databases up to March 2016. Odds ratios and 95% confidence intervals were used to identify potential associations between IL-4 genetic polymorphisms and the risk of cancer. A meta-analysis was then performed on 10,873 patients and 14,328 controls for IL-4 rs2243250 polymorphism, 3,970 patients and 5,686 controls for IL-4 rs2070874 polymorphism, and 1,896 patients and 2,526 controls for IL-4 rs79071878 polymorphism. A significant association with cancer risk was observed for rs2243250 and rs79071878 polymorphisms. In the subgroup analysis by cancer type, rs2243250 polymorphism was demonstrated to be associated with an increased risk of gastric cancer and breast cancer, rs2070874 polymorphism was correlated with leukemia and oral carcinoma, and rs79071878 polymorphism was relevant to bladder carcinoma risk. In the subgroup analysis by ethnicity, IL-4 rs2243250 polymorphism was demonstrated to be associated with cancer risk in both Caucasian and Asian populations, rs2070874 was associated with cancer risk in Asian populations, while rs79071878 polymorphism was associated with cancer risk in Caucasian populations. In conclusion, the present results suggested that the IL-4 rs2243250 and rs79071878 polymorphisms were associated with cancer susceptibility. Further subgroup analyses revealed that the effects of IL-4 gene polymorphisms on cancer risk may vary by cancer type and by ethnicity.