Decision Forest Analysis of 61 Single Nucleotide Polymorphisms in a Case-Control Study of Esophageal Cancer; a novel method

BACKGROUND: Systematic evaluation and study of single nucleotide polymorphisms (SNPs) made possible by high throughput genotyping technologies and bioinformatics promises to provide breakthroughs in the understanding of complex diseases. Understanding how the millions of SNPs in the human genome are involved in conferring susceptibility or resistance to disease, or in rendering a drug efficacious or toxic in the individual is a major goal of the relatively new fields of pharmacogenomics. Esophageal squamous cell carcinoma is a high-mortality cancer with complex etiology and progression involving both genetic and environmental factors. We examined the association between esophageal cancer risk and patterns of 61 SNPs in a case-control study for a population from Shanxi Province in North Central China that has among the highest rates of esophageal squamous cell carcinoma in the world. METHODS: High-throughput Masscode mass spectrometry genotyping was done on genomic DNA from 574 individuals (394 cases and 180 age-frequency matched controls). SNPs were chosen from among genes involving DNA repair enzymes, and Phase I and Phase II enzymes. We developed a novel adaptation of the Decision Forest pattern recognition method named Decision Forest for SNPs (DF-SNPs). The method was designated to analyze the SNP data. RESULTS: The classifier in separating the cases from the controls developed with DF-SNPs gave concordance, sensitivity and specificity, of 94.7%, 99.0% and 85.1%, respectively; suggesting its usefulness for hypothesizing what SNPs or combinations of SNPs could be involved in susceptibility to esophageal cancer. Importantly, the DF-SNPs algorithm incorporated a randomization test for assessing the relevance (or importance) of individual SNPs, SNP types (Homozygous common, heterozygous and homozygous variant) and patterns of SNP types (SNP patterns) that differentiate cases from controls. For example, we found that the different genotypes of SNP GADD45B E1122 are all associated with cancer risk. CONCLUSION: The DF-SNPs method can be used to differentiate esophageal squamous cell carcinoma cases from controls based on individual SNPs, SNP types and SNP patterns. The method could be useful to identify potential biomarkers from the SNP data and complement existing methods for genotype analyses

Abstract 3426: Recurrent breast cancer risk and physical activity

Abstract Introduction: Physical activity reduces the risk of breast cancer. However, the potential role of physical activity in recurrence of breast cancer is not well established. The aim of our study is to examine the association between physical activity and risk of recurrent breast cancer. Methods: Data was obtained from the Global Epidemiological Study (GES). The GES is an IRB approved multinational biorepository and database to assess cancer and other disease risk factors and biomarkers. In-person interviews of all subjects provided demographics, family-history and other disease related information including age, BMI, diet and physical activity. For statistical analyses, t-tests were used for continuous variables and chi-square tests for categorical variables. The association between recurrent breast cancer and physical activity was assessed using logistic regression in univariate and multivariate analyses. Results: From a total of 2435 breast cancer subjects 215 had recurrent breast cancer. The average age of subjects without recurrence was 55.62 years and those with breast cancer recurrence was 58.35 years. In univariate analysis, subjects in the highest tertile of physical activity were 39% less likely to have recurrent breast cancer compared to those who reported no physical activity [Odds Ratio: 0.61, 95% Confidence Interval: 0.40-0.93]. In multivariate analysis, subjects in the highest tertile of physical activity were 45% less likely to have recurrent breast cancer compared to those who reported no physical activity [Odds Ratio: 0.55, 95% Confidence Interval: 0.34-0.89] after adjusting for age, BMI and cancer-stage. A statistically significant dose-response for physical-activity and reduced risk of recurrent breast cancer was observed with a P-value for trend of 0.05. Conclusion: Our study suggests that physical activity reduces the risk of recurrence of breast cancer. Further studies with larger sample size are needed to confirm our findings. Citation Format: Teresa A. Lehman, Ramakrishna V. Modali, Luke D. Ratnasinghe. Recurrent breast cancer risk and physical activity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3426.</jats:p

Abstract 2765: Evaluation of family history of cancer in first-degree relatives and increased cancer risk: A multinational study

Abstract Family history of cancer is a known risk factor for several of the more prevalent cancer types. However, familial aggregation of cancer may not follow the genetic linkage pattern seen with most inherited cancer syndromes. In these instances, clustering may be due to unknown hereditary genetic mutations or to an aggregation of environmental risk factors and such clustering may still confer a significant risk. We assessed the association between family history of cancer in first-degree relatives and cancer risk among 9,122 cancer cases and 76,537 controls in a multinational study. Analyses also included evaluation of breast, colon and prostate cancer risk associated with family history of these respective cancer types. Cases were verified by physician diagnosis and all study participants were administered an in-depth survey to ascertain various demographic and lifestyle factors as well as a complete family history of cancer among first-degree relatives. Multivariable logistic regression was used to assess the association between family history of cancer and cancer risk. Among all subjects, the odds ratio (OR) for individuals with a family history of cancer was 1.79 [95% confidence interval = 1.7-1.9] after adjusting for age, gender, BMI, smoking pack years and ethnicity. Additionally, a greater cancer risk was associated with increasing number of first-degree relatives with a history of cancer. Ethnic groups studied included Caucasian-Americans, African-Americans, Hispanic/Latinas and Caucasian-Polish. All ethnic groups showed a significant association between family history of cancer and cancer risk with the highest adjusted OR of 2.65 [95% confidence interval = 2.0-3.6] among the Hispanic/Latina group. Further analyses indicated that family history of colon, breast and prostate cancer was significantly associated with an increased risk of these respective cancer types across studied ethnic groups. In particular, the adjusted ORs for breast, colon and prostate cancer risk in the Caucasian-Polish group were at least double the overall adjusted ORs for each cancer type. Our study shows that family history of cancer is a significant predictor of cancer risk especially among certain ethnic groups. In addition, family history of cancer can represent both a genetic predisposition and/or environmental exposure and risk associated with familial clustering of cancer. Citation Format: Laxmi Modali, Teresa A. Lehman, Ramakrishna Modali, Luke D. Ratnasinghe. Evaluation of family history of cancer in first-degree relatives and increased cancer risk: A multinational study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2765. doi:10.1158/1538-7445.AM2015-2765</jats:p

Serum Carotenoids and α-Tocopherol and Risk of Nonmelanoma Skin Cancer

Abstract Background: Carotenoids and tocopherols have been hypothesized to protect against cancer. Methods: We prospectively evaluated associations of several carotenoids and α-tocopherol with risk of nonmelanoma skin cancer using serum collected at baseline from 302 subjects in the Isotretinoin-Basal Cell Carcinoma Prevention Trial. All subjects had at least two BCCs in the 5 years prior to randomization. During 5 years of follow-up, 70 subjects did not develop a nonmelanoma skin cancer, 221 developed a BCC, and 85 developed a squamous cell carcinoma (SCC). Cox proportional hazards models were used to estimate risk ratios. Models were stratified by clinical center and gender and adjusted for age, solar damage, skin type, number of prior BCCs and/or SCCs, treatment group, body mass index, and serum low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. Results: Risk of developing a subsequent BCC was not related to serum levels of any of the carotenoids measured or to α-tocopherol. Serum levels of α-carotene, β-carotene, lycopene, and α-tocopherol also were not independently related to risk of a subsequent SCC. However, serum lutein, zeaxanthin, and β-cryptoxanthin were positively related to SCC risk; risk ratios for subjects in the highest versus lowest tertiles of these micronutrients were 1.63 [95% confidence interval (95% CI) 0.88-3.01; P for trend = 0.01], 2.40 (95% CI 1.30-4.42; P for trend = 0.01), and 2.15 (95% CI 1.21-3.83; P for trend = 0.09), respectively. Conclusion: Additional research is needed on the relationship of carotenoids to SCC risk in the general population and in subsets of the population who are at increased risk.</jats:p