Single-Nucleotide Polymorphisms and Markers of Oxidative Stress in Healthy Women

Purpose There is accumulating evidence that oxidative stress is an important contributor to carcinogenesis. We hypothesized that genetic variation in genes involved in maintaining antioxidant/ oxidant balance would be associated with overall oxidative stress. Methods We examined associations between single nucleotide polymorphisms (SNPs) in MnSOD, GSTP1, GSTM1, GPX1, GPX3, and CAT genes and thiobarbituric acid-reactive substances (TBARS), a blood biomarker of oxidative damage, in healthy white women randomly selected from Western New York (n = 1402). We used general linear models to calculate age-adjusted geometric means of TBARS across the variants. We also examined the associations within strata of menopausal status. Results For MnSOD, being heterozygous was associated with lower geometric means of TBARS (less oxidative stress), 1.28 mg/dL, compared to homozygous T-allele or homozygous Callele, 1.35 mg/dL, and 1.31 mg/dL correspondingly (p for trend = 0.01). This difference remained among postmenopausal women, 1.40 mg/dL for TT, 1.32 mg/dL for TC, and 1.34mg/dL for CC (p for trend 0.015); it was attenuated among premenopausal women. SNPs in the other genes examined (GSTP1, GSTM1, GPX1, GPX3, and CAT) were not associated with TBARS. Conclusions Our findings suggest that genetic variation in MnSOD gene may be associated with oxidative status, particularly among postmenopausal women

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

Abstract 870: Physical activity, diet and ovarian cancer risk

Abstract Physical activity and diet are modifiable risk factors for most cancers. Previous studies of the association between physical activity, diet and ovarian cancer risk have yielded mixed results. We evaluated the association between physical activity, diet and ovarian cancer risk among 578 ovarian cancer cases and 7188 non-cancer controls in the Global Epidemiology Study (GES). The GES is linked to the Global Repository that houses biomaterial. For ovarian cancer, newly diagnosed subjects provided informed consent and were asked about physical activity and diet during in-person interviews. The multivariate-adjusted odds ratio (OR) was 0.6 (95% confidence interval (95% CI): 0.5-0.8) for women who reported physical activity greater than 160 minutes per week after adjusting for age, race, BMI and pack-years of smoking compared to women who reported less than 30 minutes of physical activity. Women who were in the highest tertile of vegetables consumers were at 20% reduced risk for ovarian cancer compared to the lowest tertile [OR:0.8, 95% CI: 0.6-0.9]. Individuals who were in the highest tertile of dairy consumers were at 40% reduced risk for ovarian cancer compared to the lowest tertile [OR: 0.6, 95% CI: 0.5-0.8]. For meat consumption, individuals who were in the highest tertile were at 60% increased risk for ovarian cancer compared to the lowest tertile [OR: 1.6, 95% CI: 1.3-2.0]. Results from our study suggest that physical activity and diet are modifiable risk factors for ovarian cancer. Citation Format: Teresa A. Lehman, Ramakrishna V. Modali, Luke Ratnasinghe. Physical activity, diet and ovarian cancer risk. [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 870. doi:10.1158/1538-7445.AM2015-870</jats:p

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 860: Effects of breastfeeding and oral contraception use on the risk of breast cancer recurrence: A multinational study

Abstract Introduction: Breastfeeding (BF) decreases and oral contraceptive (OCP) increases the incidence of breast cancer (BC). However, their role in the recurrence of breast cancer (rBC) has not been established. The aim of our study was to examine the association of maternal factors in the rBC. Methods: Data were obtained from the Global Epidemiological Study (GES), an IRB approved multinational biorepository and database to assess disease risk factors. Pts provided their personal history, age, BMI, age of first pregnancy, BF, number of children breastfed, radiation exposure (RE), years of OCP use, benign breast disease (BD), hysterectomy, hormone replacement therapy (HRT) and rBC. The t-test and chi-square test were used for continuous and categorical variables, respectively. The association [adjusted odds ratio (aOR)] between rBC and each risk factor was obtained using logistic regression after adjusting for all the variables including stage of cancer. Results: A total of 2546 patients were surveyed, of which 218 patients had rBC later in life. The average age of pts with recurrence was 54 yrs and those without rBC was 56 yrs. Of the total, 73.5% had BF, 25% had used OCP, 17.3% used HRT, 5.6% had RE, 16.6% had a hysterectomy, and 16% had BD. In multivariate analysis, age, BF, OCP and RE each had significant impacts on the rBC. Pts who did not BF had a 3-fold increased risk of recurrence compared to those who breastfed at least 3 children [aOR of 2.9 (1.7-4.9)]. Pts who did not use OCPs were 53% less likely to have rBC compared to those who used OCPs [aOR of 0.47 (0.32-0.69)]. A statistically significant dose-effect for number of children breastfed and rBC, and years of OCPs usage and rBC was found. BMI, HRT, hysterectomy, BD, and age at first pregnancy did not have an effect on rBC. Conclusion: Our study suggests that breastfeeding decreases the risk of recurrence of breast cancer, while OCP usage increases the risk of recurrence of breast cancer. Further studies are needed to validate our results. Predictors of recurrence of breast cancer (rBC)Variablesβ EstimateAdjusted OR (CI)p-valueAge0.0221.02 (1.008-1.03)0.002Breastfed (BF, none vs. &amp;gt;3 children)1.062.9 (1.7-4.9)&amp;lt;0.0001Breastfed (BF, &amp;lt; 3 vs. &amp;gt; 3 children)0.742.09 (1.2-3.5)0.006Oral Contraceptive use (OCP, no vs. yes)-0.7430.47 (0.32-0.69)0.0001Radiation exposure (RE, no vs. yes)-1.310.26 (0.16- 0.13)&amp;lt;0.0001HRT (no vs. yes)0.41.49 (0.96-2.3)0.07 Citation Format: Teresa A. Lehman, Mohammed Shaik, Ramakrishna V. Modali, Borys Hrinczenko. Effects of breastfeeding and oral contraception use on the risk of breast cancer recurrence: 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 860. doi:10.1158/1538-7445.AM2015-860</jats:p

Supplementary Table 6 from Identification of a Functional SNP in the 3′UTR of CXCR2 That Is Associated with Reduced Risk of Lung Cancer

&lt;p&gt;Relationship between rs1126579 and lung cancer survival.&lt;/p&gt;</jats:p

Supplementary Figure 1 from Identification of a Functional SNP in the 3′UTR of CXCR2 That Is Associated with Reduced Risk of Lung Cancer

&lt;p&gt;Predicted modulation of miR-138-1* binding to CXCR2 mRNA by rs1126579.&lt;/p&gt;</jats:p

Supplementary Figure 3 from Identification of a Functional SNP in the 3′UTR of CXCR2 That Is Associated with Reduced Risk of Lung Cancer

&lt;p&gt;CXCR2 isoform expression in human lung adenocarcinoma and squamous cell carcinoma tissue.&lt;/p&gt;</jats:p