Type of article: Full paper 12 Running head: Clostridioides difficile antibodies and colorectal cancer 13 Abstract 28 29Dysbiosis, defined as an imbalance in the gut microbiota caused by too few beneficial 30 bacteria and an overgrowth of bad bacteria, yeast, and/or parasites, is now being associated with 31 several diseases, including the development of colorectal carcinoma (CRC). In this study, the 32 potential association of Clostridioides difficile (formerly Clostridium difficile) with CRC was 33 investigated. Plasma samples obtained from preoperative histologically confirmed CRC patients 34 (n=39) and their age-and sex-matched clinically healthy controls (n=39) were analyzed for 35 antibodies to toxin B of C. difficile (anti-tcdB) by enzyme-linked immunosorbent assay (ELISA). 36A significantly greater number (p=0.012) of CRC cases (n=26/39, 66.7%) had anti-tcdB IgG 37 levels above the cutoff value compared with controls (n=12/39, 30.8%). Eight cases (8/39, 38 20.5%) and none of the controls registered anti-tcdB IgA levels above the cutoff value 39 (p=0.0039). Anti-tcdB IgG and IgA levels were not shown to be significantly associated with 40 tumor grade or tumor stage. Anti-tcdB IgG showed 66.7% sensitivity and 69.2% specificity. For 41 anti-tcdB IgA, sensitivity and specificity were 20.5% and 100%, respectively. The positive 42 predictive values for anti-tcdB IgA and IgG were 100% and 68.4%, respectively. The anti-tcdB 43 IgA and IgG negative predictive values were 55.7% and 67.5%, respectively. The results suggest 44 the potential association of C. difficile with CRC and anti-tcdB levels, particularly the IgA level. 45Hence, anti-tcdB antibodies can be candidate serologic markers for CRC. 46 47 48 51Colorectal cancer (CRC) is one of the most prevalent cancers in the world [1]. Diet, 52 particularly the consumption of poultry and animal products, has been linked to increased cases 53 of CRC [2]. Imbalance in chromosome number, genomic amplifications in the subchromosomal 54 region, and high frequency of heterozygous loss also lead to mutation and malignant transition of 55 cells in the colon [3, 4]. 56In addition, the potential role of gut microbes in CRC development has been a hot topic 57 lately. Several hypotheses have emerged on how these bacteria promote carcinogenesis. 58 Dysbiosis and alterations in the normal microbial community remodel the whole microbiome, 59 initiating inflammation and cell differentiation which could eventually lead to cancer [5]. The 60 "driver-passenger" model proposes that some bacteria classified as "bacterial drivers" initiate the 61 development of colonic tumors through gene damage, stimulating the colonization of passenger 62 bacteria in the tumoral microenvironment [5, 6]. Some "keystone pathogens" that emerge during 63 dysbiosis and are likely to be part of carcinogenesis include Bacteroides, Enterococcus, 64 Fusobacterium, Streptococcus, Escherichia coli, and Clostridium [5, 7]. 65 Clostridioides difficile (formerly Clostridium difficile) is a gram-positive, ana...

A relationship between increased ALT incidence in premarketing clinical trials and postmarketing published case reports exists.

Background:The association of genetic polymorphisms with cancer development has been shown to be race- and tumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genes are associated with breast cancer among selected Filipinos. Methods:A total of 136 histologically confirmed breast cancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from blood samples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results:The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantly different (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that risk for breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1 positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1 null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion:This study suggests that variants of GSTM1 and GSTT1 may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when these genotypes were combined with lifestyle or environmental factors.

Background:The identification of cancer-associated single nucleotide polymorphisms (SNP) and mutation genes is a promising approach in recognizing individuals who are at risk of developing cancer. Hence, this study was conducted to determine the association between XRCC4 c.1394G>T SNP and breast cancer development among Filipinos. Methods: Genotyping for XRCC4 c.1394G>T SNP was performed on breast cancer patients (n=103) and their age-and sex-matched clinically healthy controls (n=103) by polymerase chain reaction -restriction fragment length polymorphism. Results: Significant difference in genotype (p=0.007) and allele (p=0.003) frequencies in XRCC4 c.1394G>T was observed between the breast cancer cases and controls. Carriers of the XRCC4 c.1394 G>T genotype were observed to have significantly higher risk of developing breast cancer compared to individuals with T/T genotype (OR=2.67, 95% CI: 1. 36 -5.25). XRCC4 c.1394G>T combined with passive smoking may also significantly increase risk of breast cancer (OR=14.73; 95% CI= 9.88-18.86). Conclusion: XRCC4 c. 1394G>T may be associated with breast cancer development among Filipinos.