{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T01:00:28Z","timestamp":1760317228689,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T00:00:00Z","timestamp":1350950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Toxicity from neoadjuvant chemoradiation therapy (NT) increases morbidity and limits therapeutic efficacy in patients with rectal cancer. The objective of this study was to determine whether specific polymorphisms in genes associated with rectal cancer response to NT were correlated with NT\u2010related toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>One hundred thirty\u2010two patients with locally advanced rectal cancer received NT followed by surgery. All patients received 5\u2010fluorouracil (5\u2010FU) and radiation (RT), and 80 patients also received modified infusional 5\u2010FU, folinic acid, and oxaliplatin chemotherapy (mFOLFOX\u20106). Grade \u22653 adverse events (AEs) that occurred during 5\u2010FU\/RT and during combined 5\u2010FU\/RT + mFOLFOX\u20106 were recorded. Pretreatment biopsy specimens and normal rectal tissues were collected from all patients. DNA was extracted and screened for 22 polymorphisms in 17 genes that have been associated with response to NT. Polymorphisms were correlated with treatment\u2010related grade \u22653 AEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Overall, 27 of 132 patients (20%) had grade \u22653 AEs; 18 patients had a complication associated only with 5\u2010FU\/RT, 3 patients experienced toxicity only during mFOLFOX\u20106, and 6 patients had grade \u22653 AEs associated with both treatments before surgery. Polymorphisms in the genes x\u2010ray repair complementing defective repair in Chinese hamster cells 1 (<jats:italic>XRCC1<\/jats:italic>), xeroderma pigmentosum group D (<jats:italic>XPD<\/jats:italic>), and tumor protein 53 (<jats:italic>TP53<\/jats:italic>) were associated with grade \u22653 AEs during NT (<jats:italic>P<\/jats:italic> &lt; .05). Specifically, 2 polymorphisms\u2014an arginine\u2010to\u2010glutamine substitution at codon 399 (Q399R) in <jats:italic>XRCC1<\/jats:italic> and a lysine\u2010to\u2010glutamine substitution at codon 751 (K751Q) in <jats:italic>XPD<\/jats:italic>\u2014were associated with increased toxicity to 5\u2010FU\/RT (<jats:italic>P<\/jats:italic> &lt; .05), and an arginine\u2010to\u2010proline substitution at codon 72 (R72P) in <jats:italic>TP53<\/jats:italic> was associated with increased toxicity to mFOLFOX\u20106 (<jats:italic>P<\/jats:italic> = .008).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Specific polymorphisms in <jats:italic>XRCC1<\/jats:italic>, <jats:italic>XPD<\/jats:italic>, and <jats:italic>TP53<\/jats:italic> were associated with increased toxicity to NT in patients with rectal cancer. The current results indicated that polymorphism screening may help tailor treatment for patients by selecting therapies with the lowest risk of toxicity, thus increasing patient compliance. Cancer 2013. \u00a9 2012 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.27862","type":"journal-article","created":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T12:39:08Z","timestamp":1350995948000},"page":"1106-1112","source":"Crossref","is-referenced-by-count":12,"title":["Gene polymorphisms predict toxicity to neoadjuvant therapy in patients with rectal cancer"],"prefix":"10.1002","volume":"119","author":[{"given":"Marjun P.","family":"Duldulao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca 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