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WISP1 polymorphisms contribute to platinum-based chemotherapy toxicity in lung cancer patients.

Chen J, Yin J, Li X, Wang Y, Zheng Y, Qian C, Xiao L, Zou T, Wang Z, Liu J, Zhang W, Zhou H, Liu Z - Int J Mol Sci (2014)

Bottom Line: We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses.Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity.Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. cj1028@csu.edu.cn.

ABSTRACT
Platinum-based chemotherapy toxicity is always one of the serious problems from which lung cancer patients suffer. The genetic polymorphism of WISP1 was revealed to be associated with susceptibility and platinum-based chemotherapy response in our previous studies. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with platinum-based chemotherapy toxicity in lung cancer patients. A total of 412 lung cancer patients were enrolled in this study, and 28 polymorphisms of the WISP1 gene were genotyped by SequenomMassARRAY. We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses. Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity. Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer. Genotypes of WISP1 may be novel and useful biomarkers for predicting platinum-based chemotherapy toxicity in lung cancer patients.

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Stratification analyses of the associations of WISP1 rs2929965, rs2929969, rs2929970, rs2929973 and rs754958 polymorphisms with the overall chemotherapy toxicity of lung cancer. Each box and horizontal line represents the values of OR and 95% CI. NSCLC, non-small cell lung carcinoma; SCLC, small cell lung carcinoma. * p < 0.05.
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ijms-15-21011-f001: Stratification analyses of the associations of WISP1 rs2929965, rs2929969, rs2929970, rs2929973 and rs754958 polymorphisms with the overall chemotherapy toxicity of lung cancer. Each box and horizontal line represents the values of OR and 95% CI. NSCLC, non-small cell lung carcinoma; SCLC, small cell lung carcinoma. * p < 0.05.

Mentions: The 28 polymorphisms of WISP1 were not statistically significantly related to increased risk of overall severe toxicity in all three models (Table S1). However, there were five SNPs related to the toxicity in subgroup analyses. As shown in Figure 1, WISP1 rs2929965 polymorphism was related to the overall toxicity of NSCLC patients in the additive model; WISP1 rs2929969 and rs2929973 were related to the overall toxicity of SCLC in additive and dominant models and related to the toxicity of NSCLC in the dominant model. Additionally, they were also related to overall toxicity in lung cancer patients ≤55 years old in the recessive model. WISP1 rs2929970 was related to overall toxicity in patients >55 years old and in NSCLC and SCLC patients in the dominant model, as well as in patients ≤55 years old in the recessive model. WISP1 rs754958 was related to the overall toxicity of SCLC patients in additive and dominant models and related to the overall toxicity of NSCLC in the dominant model. In conclusion, lung cancer patients ≤55 years old carrying the A allele of (rs2929969, rs2929970) or the G allele of rs2929973; patients >55 years old carrying the G allele of rs2929970; NSCLC patients carrying the T allele of (rs2929965, rs2929973, rs754958) or the G allele of (rs2929969, rs2729970); SCLC patients carrying the A allele of (rs2929965, rs2929970), or the G allele of rs2929973, or the C allele of rs754958 suffered more risk of Grade 3 or 4 toxicity overall for platinum-based chemotherapy.


WISP1 polymorphisms contribute to platinum-based chemotherapy toxicity in lung cancer patients.

Chen J, Yin J, Li X, Wang Y, Zheng Y, Qian C, Xiao L, Zou T, Wang Z, Liu J, Zhang W, Zhou H, Liu Z - Int J Mol Sci (2014)

Stratification analyses of the associations of WISP1 rs2929965, rs2929969, rs2929970, rs2929973 and rs754958 polymorphisms with the overall chemotherapy toxicity of lung cancer. Each box and horizontal line represents the values of OR and 95% CI. NSCLC, non-small cell lung carcinoma; SCLC, small cell lung carcinoma. * p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264209&req=5

ijms-15-21011-f001: Stratification analyses of the associations of WISP1 rs2929965, rs2929969, rs2929970, rs2929973 and rs754958 polymorphisms with the overall chemotherapy toxicity of lung cancer. Each box and horizontal line represents the values of OR and 95% CI. NSCLC, non-small cell lung carcinoma; SCLC, small cell lung carcinoma. * p < 0.05.
Mentions: The 28 polymorphisms of WISP1 were not statistically significantly related to increased risk of overall severe toxicity in all three models (Table S1). However, there were five SNPs related to the toxicity in subgroup analyses. As shown in Figure 1, WISP1 rs2929965 polymorphism was related to the overall toxicity of NSCLC patients in the additive model; WISP1 rs2929969 and rs2929973 were related to the overall toxicity of SCLC in additive and dominant models and related to the toxicity of NSCLC in the dominant model. Additionally, they were also related to overall toxicity in lung cancer patients ≤55 years old in the recessive model. WISP1 rs2929970 was related to overall toxicity in patients >55 years old and in NSCLC and SCLC patients in the dominant model, as well as in patients ≤55 years old in the recessive model. WISP1 rs754958 was related to the overall toxicity of SCLC patients in additive and dominant models and related to the overall toxicity of NSCLC in the dominant model. In conclusion, lung cancer patients ≤55 years old carrying the A allele of (rs2929969, rs2929970) or the G allele of rs2929973; patients >55 years old carrying the G allele of rs2929970; NSCLC patients carrying the T allele of (rs2929965, rs2929973, rs754958) or the G allele of (rs2929969, rs2729970); SCLC patients carrying the A allele of (rs2929965, rs2929970), or the G allele of rs2929973, or the C allele of rs754958 suffered more risk of Grade 3 or 4 toxicity overall for platinum-based chemotherapy.

Bottom Line: We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses.Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity.Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. cj1028@csu.edu.cn.

ABSTRACT
Platinum-based chemotherapy toxicity is always one of the serious problems from which lung cancer patients suffer. The genetic polymorphism of WISP1 was revealed to be associated with susceptibility and platinum-based chemotherapy response in our previous studies. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with platinum-based chemotherapy toxicity in lung cancer patients. A total of 412 lung cancer patients were enrolled in this study, and 28 polymorphisms of the WISP1 gene were genotyped by SequenomMassARRAY. We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses. Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity. Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer. Genotypes of WISP1 may be novel and useful biomarkers for predicting platinum-based chemotherapy toxicity in lung cancer patients.

Show MeSH
Related in: MedlinePlus