Cyclin D1 (CCND1) G870A polymorphism has been known to be a risk factor in multiple cancers. Cyclin D1 is a cell cycle regulator frequently mutated, amplified and overexpressed in a variety of tumors. Activation and over expression of CCND1 have been found in variety of tumors and alterations in CCND1 are thought to be involved in carcinogensis. CCND1 polymorphism A870G interferes with splicing and studies showed DNA damage in cells from subjects with ‘A’ allele to bypass G1/S check point of the cell cycle control mechanism more easily than damage in cells with G allele (wild type). A single base pair polymorphism (exon 4, G870A) in the CCND1 gene affects gene splicing. This identification and validation of contributing genetic factors such as single-nucleotide polymorphisms (SNPs) represents a critical step in the advance toward personalized medicine. Several gene expression correlation studies have been done but to our knowledge studies have not been reported on SNP’s of ERBB2 gene, ESR gene and CCND1 combined effect correlating with high risk. In this study, we examined the relationship between ERBB2 (codon 655), Estrogen receptor (ER Intron1 T<C) and cyclin D1 (Exon 4) polymorphic additive effect in cancers more specific to breast cancer. Genomic DNA was extracted from whole blood samples collected on study. The SNPs were tested by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. Our results show individuals carrying CCND1 ‘A allele in combination with variant ERBB2/BsmAI uncut allele are significantly high (P<0.004) in cancer patients (N=232) as compared to controls. (N=222). Similarly individuals carrying CCND1 Variant ‘A ‘ allele in combination with ESR ‘C’ Allele showed high frequency with p<0.009. Both these combinations showed a strong and significant association with cancer but individually, ERBB2 variant did not show any significant association, ESR gene showed a borderline association and CCND1 showed strong association independent of these two gene polymorphisms. Earlier few studies have shown no association of ERBB2 mutation in agreement with the previous reports. In conclusion our data suggests that in complex diseases a single gene may not contribute to show its effect but in combination may show a profound effect in evaluating the risk. Citation Format: Radhika Gade Andavolu, Olivia Rodriguez, Anastasia Al Rubakovic, Catherine Stafford, Murthy V. Andavolu. Combined effect of multiple gene polymorphisms on cancer risk stratification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3267. doi:10.1158/1538-7445.AM2017-3267

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The pathogenesis of cancer involves environmental factors in addition to hereditary factors. Recent studies have pointed to a potential role for inflammation in prostatic carcinogenesis and tumor progression. An important factor is the development of chronic inflammation in the prostate due to a number of potential causes including infections, dietary factors, hormonal changes and/or other unknown environmental exposures. In this study we investigated the possible association between single nucleotide polymorphisms in the interleukin IL‐1B (C>T), tumor necrosis factor (308G>A), RANTES‐403, GSTP1 exon 5 polymorphic site (Ile105àVal), PPARG (Pro12Ala) genes also two STR polymorphic marker GSTP1 (penta‐nucleotide repeat at promoter regions) and a pyrimidine‐rich penta‐nucleotide repeat length polymorphism, CD4‐1188 (TTTTC) and the risk for developing prostate cancer. Our study is comprised of 134 prostate cancer cases and age, gender and race matched 178 normal healthy controls. These genes are known to be important for inflammation of prostate and common allelic variants have been shown to have a biological effect. Hence, we searched for a possible association between SNP polymorphisms and STR polymorphic allele gene frequencies obtained in prostate cancer patients and compared with those of a normal control population, looking for allelic associations between any of these polymorphic loci and prostate cancer risk. Strong association between GSTP1, CD4, RANTES (p<0.001), a high variation in allelic frequency of mutant IL1B, TNF and PPARG (p=NS) and prostate cancer risk are observed. Genetic associations of disease and genetic variations in inflammatory genes are often relatively modest, it is likely that polymorphisms in multiple inflammatory genes cooperate in an additive or synergistic manner to impact disease risk Because genetic associations of disease and genetic variations in inflammatory genes are often relatively modest, it is likely that polymorphisms in multiple inflammatory genes cooperate in an additive or synergistic manner to impact disease risk. The possible role of inflammation and gene associations with prostate cancer risk will be discussed.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.