Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy

Hong Tae Kim, Jong Eun Lee, Eun Soon Shin, Yeon Kyeong Yoo, Jae Hwa Cho, Min Hye Yun, Yeul Hong Kim, Se Kyu Kim, Hyun Jung Kim, Tae Won Jang, Seung Min Kwak, Chul Soo Kim, Jeong Seon Ryu

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Abstract

Purpose: To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. Patients and Methods: We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16%), IIIB (31%), and IV (53%). Results: The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3%) of the patients had squamous cell carcinomas and 137 (45.7%) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95% CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 × 10-5), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). Conclusion: These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.

Original languageEnglish
Pages (from-to)5972-5979
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number36
DOIs
Publication statusPublished - 2008 Dec 20

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Platinum
Non-Small Cell Lung Carcinoma
Haplotypes
Drug Therapy
Survival
Squamous Cell Carcinoma
Combination Drug Therapy
Adenocarcinoma
BRCA1 Gene
Germ Cells
Weight Loss
Radiotherapy
Body Weight

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy. / Kim, Hong Tae; Lee, Jong Eun; Shin, Eun Soon; Yoo, Yeon Kyeong; Cho, Jae Hwa; Yun, Min Hye; Kim, Yeul Hong; Kim, Se Kyu; Kim, Hyun Jung; Jang, Tae Won; Kwak, Seung Min; Kim, Chul Soo; Ryu, Jeong Seon.

In: Journal of Clinical Oncology, Vol. 26, No. 36, 20.12.2008, p. 5972-5979.

Research output: Contribution to journalArticle

Kim, HT, Lee, JE, Shin, ES, Yoo, YK, Cho, JH, Yun, MH, Kim, YH, Kim, SK, Kim, HJ, Jang, TW, Kwak, SM, Kim, CS & Ryu, JS 2008, 'Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy', Journal of Clinical Oncology, vol. 26, no. 36, pp. 5972-5979. https://doi.org/10.1200/JCO.2008.16.6496
Kim, Hong Tae ; Lee, Jong Eun ; Shin, Eun Soon ; Yoo, Yeon Kyeong ; Cho, Jae Hwa ; Yun, Min Hye ; Kim, Yeul Hong ; Kim, Se Kyu ; Kim, Hyun Jung ; Jang, Tae Won ; Kwak, Seung Min ; Kim, Chul Soo ; Ryu, Jeong Seon. / Effect of BRCA1 haplotype on survival of non-small-cell lung cancer patients treated with platinum-based chemotherapy. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 36. pp. 5972-5979.
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abstract = "Purpose: To determine whether germ-line variations in BRCA1 affect outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum combination chemotherapy. Patients and Methods: We evaluated the associations of four tagging BRCA1 polymorphisms and their haplotypes with treatment outcome in 300 NSCLC patients at stages IIIA (16{\%}), IIIB (31{\%}), and IV (53{\%}). Results: The median age was 63 years (range, 28 to 89 years). Histologically, 139 (46.3{\%}) of the patients had squamous cell carcinomas and 137 (45.7{\%}) had adenocarcinomas. Patient median survival time (MST) was 13.0 months. We observed no significant association between any of the tagging polymorphisms [S1613G, IVS13-1893 (A>C), IVS12-1207 (C>T), and IVS12+112 (C>A)] and overall survival. Of the five haplotypes evaluated (AACC, AACA, GCTC, GATC, and AATC), the survival of patients with two copies of the AACC (wild-type) haplotype was significantly shorter than that of patients with zero to one copies (MST, 8.47 v 14.57 months; log-rank P = .0066), even after adjustment for body weight loss, performance status, stage, second-line treatment, and radiation therapy (hazard ratio = 2.097; 95{\%} CI, 1.339 to 3.284). The survival of patients with squamous cell carcinoma and two copies was significantly shorter than that of other patients with squamous cell carcinoma (MST, 6.8 v 15.3 months; log-rank P = 3.6 × 10-5), whereas differences in survival between the two adenocarcinoma groups was not significant (log-rank P = .677). Conclusion: These findings suggest that the AACC haplotype of the BRCA1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.",
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AU - Lee, Jong Eun

AU - Shin, Eun Soon

AU - Yoo, Yeon Kyeong

AU - Cho, Jae Hwa

AU - Yun, Min Hye

AU - Kim, Yeul Hong

AU - Kim, Se Kyu

AU - Kim, Hyun Jung

AU - Jang, Tae Won

AU - Kwak, Seung Min

AU - Kim, Chul Soo

AU - Ryu, Jeong Seon

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