Authors: Sonam Tulsyan1, Pankaj Chaturvedi1, Gaurav Agarwal2, Punita Lal3, Sushma Agrawal3, Rama Devi Mittal4, Balraj Mittal1

Title: Pharmaco-genetic influence of GST polymorphisms on anthracyclines based chemotherapy response and toxicity in breast cancer patients: A multi-analytical approach

Running Title: GST polymorphisms and breast cancer treatment outcomes

1Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

2Department of Endocrine & Breast Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

3Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

4Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

Address of correspondence to:

Dr. Balraj Mittal,

Sanjay Gandhi Post Graduate Institute of Medical Sciences,

Raebareli road, Lucknow-226 014, India.

E-mail: .

Ph.+91-522-249-4322.

Fax. +91-522-2668973

Genotype / Anemia n(%)=95 (45.9) / No Anemia n(%)=112 (54.1) / #OR (95%CI) / P value
GSTM1
Present / 62(65.3) / 66(58.9.) / Reference / -
Null / 33(34.7) / 46(41.1) / 0.73(0.40-1.36) / 0.335
GSTT1
Present / 76(80.0) / 96(85.7) / Reference / -
Null / 19(20.0) / 16(14.3) / 1.51(0.67-3.36) / 0.311
GSTP1 Ile105Val (rs1695)
Ile/Ile / 34(35.8) / 54(48.2) / Reference / -
Ile/Val / 52(54.7) / 48(42.9) / 2.12(1.13-4.00) / 0.019
Val/Val / 9(9.5) / 10(8.9) / 1.38(0.47-4.03) / 0.552
Ile/Val + Val/Val / 61(64.2) / 58(51.8) / 1.97(1.08-3.62) / 0.027
Alleles
Ile / 120(63.2) / 156(69.6) / Reference / -
Val / 70(36.8) / 68(30.4) / 1.42(0.91-2.20) / 0.116
OR= Odds Ratio; CI= Confidence Interval
Significant P Values are in bold
# Adjusted OR for age, menstrual status, TNM stage, histology, tumour grade, hormone receptor and Her 2 neu status.

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Genotype / Leucopenia
n(%)=51 (24.6) / No leucopenia
n(%)=156 (75.4) / #OR (95%CI) / P value
GSTM1
Present / 33(64.7) / 95(60.9) / Reference / -
Null / 18(35.3) / 61(39.1) / 0.84(0.40-1.75) / 0.645
GSTT1
Present / 42(82.4) / 130(83.3) / Reference / -
Null / 9(17.6) / 26(16.7) / 1.01(0.39-2.59) / 0.975
GSTP1 Ile105Val (rs1695)
Ile/Ile / 19(37.3) / 69(44.2) / Reference / -
Ile/Val / 24(47.1) / 76(48.7) / 1.19(0.56-2.55) / 0.640
Val/Val / 8(15.7) / 11(7.1) / 2.67(0.85-8.40) / 0.092
Ile/Val + Val/Val / 32(62.7) / 87(55.8) / 1.39(0.67-2.85) / 0.369
Alleles
Ile / 62(60.8) / 214(68.6) / Reference / -
Val / 40(39.2) / 98(31.4) / 1.42(0.86-2.36) / 0.168
OR= Odds Ratio; CI= Confidence Interval
# Adjusted OR for age, menstrual status, TNM stage, histology, tumour grade, hormone receptor and Her 2 neu status.

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Suppl Table 3: Genotypic and allelic frequencies of GSTT1, GSTM1 and GSTP1Ile105Val (rs1695)polymorphisms among patients with febrile neutropenia who had dose delay/reduction

Genotype / Dose delay/reduction, n(%)=30 (14.5 / No Dose delay/reduction, n(%)=177 (85.5) / #OR(95%CI) / P value
GSTM1
Present / 19(63.3) / 109(61.6) / Reference / -
Null / 11(36.7) / 68(38.4) / 0.96(0.40-2.25) / 0.928
GSTT1
Present / 26(86.7) / 146(82.5) / Reference / -
Null / 4(13.3) / 31(17.5) / 0.63(0.19-2.08) / 0.451
GSTP1 Ile105Val (rs1695)
Ile/Ile / 11(36.7) / 77(43.5) / Reference / -
Ile/Val / 16(53.3) / 84(47.5) / 1.53(0.63-3.71) / 0.346
Val/Val / 3(10.0) / 16(9.0) / 0.85(0.16-4.41) / 0.849
Ile/Val + Val/Val / 19(63.3) / 100(56.5) / 1.40(0.59-3.34) / 0.440
Alleles
Ile / 38(63.3) / 238(67.2) / Reference / -
Val / 22(36.7) / 116(32.8) / 1.11(0.60-2.03) / 0.738
OR= Odds Ratio; CI= Confidence Interval
# Adjusted OR for age, menstrual status, TNM stage, histology, tumour grade, hormone receptor and Her 2 neu status.

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