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Table 3 Mediation effect of HOMA-IR on the relationship between glucose metabolism–relevant SNPs and breast cancer risk, stratified by obesity status and obesity-related factors

From: Effect of genetic variants and traits related to glucose metabolism and their interaction with obesity on breast and colorectal cancer risk among postmenopausal women

SNP

Nearest gene

Effect allele/Other allele

Favorable Energy Balance Group

Unfavorable Energy Balance Group

Direct effect

Indirect effect

Total effect

Direct effect

Indirect effect

Total effect

Breast cancer risk in relation to SNP through pathways other than HOMA-IR

Breast cancer risk in relation to SNP through HOMA-IR

Breast cancer risk in relation to SNP

Breast cancer risk in relation to SNP through pathways other than HOMA-IR

Breast cancer risk in relation to SNP through HOMA-IR

Breast cancer risk in relation to SNP

HRa

95% CI

Effect sizea

95% CI

HRa

95% CI

HRa

95% CI

Effect sizea

95% CI

HRa

95% CI

BMIb

 rs560887

G6PC2

T/C

1.17

(0.93–1.46)

<0.001

(−0.003–0.003)

1.12

(0.90–1.39)

1.35

(1.04–1.76)

<0.001

(−0.02–0.02)

1.35

(1.05–1.74)

Waistc

 rs560887

G6PC2

T/C

1.11

(0.86–1.42)

−0.003

(−0.01–0.01)

1.10

(0.86–1.40)

1.39

(1.10–1.77)

−0.002

(−0.01–0.01)

1.33

(1.06–1.66)

Waist/hip Ratiod

 rs560887

G6PC2

T/C

1.11

(0.72–1.12)

0.001

(−0.01–0.004)

1.10

(0.89–1.36)

1.50

(1.14–1.97)

−0.001

(−0.01–0.01)

1.42

(1.10–1.85)

 rs35767

IGF1

A/G

0.92

(0.69–1.24)

0.001

(−0.01–0.003)

0.93

(0.70–1.23)

1.42

(1.02–1.98)

−0.002

(−0.01–0.01)

1.48

(1.08–2.03)

Dietary fat intakee

 rs560887

G6PC2

T/C

1.16

(0.96–1.41)

0.01

(−0.01–0.003)

1.14

(0.95–1.37)

1.59

(1.08–2.34)

0.003

(−0.02–0.02)

1.59

(1.10–2.31)

  1. BMI body mass index, CI confidence interval, HOMA-IR homeostatic model assessment–insulin resistance, HR hazard ratio, SNP single–nucleotide polymorphism, w/h ratio waist-to-hip ratio
  2. Note: Proportions explained by HOMA-IR for SNP–breast cancer risk association for rs560887 (41.7%,10%, 10%, and 14.3% among non-obese group [BMI < 30, waist ≤88 cm, w/h ≤ 0.85, and <40% calories from fat, respectively]; 0%, 18.1%, 19.1%, and 0% among obese-group [BMI ≥ 30, waist >88 cm, w/h > 0.85, and ≥40% calories from fat, respectively]), and for rs35767 (0.4% in w/h ≤ 0.85; 11.9% in w/h > 0.85). Only SNPs having statistically significant results are included. Numbers in bold face are statistically significant
  3. aMultivariate regression was adjusted by covariates (age, education, family history of diabetes mellitus, family history of breast cancer, cardiovascular disease ever, hypertension ever, high cholesterol requiring pills ever, total Healthy Eating Index-2005 score, dietary alcohol and total sugars per day, smoking status, lifetime partner, depressive symptom, oral contraceptive use, history of hysterectomy or oophorectomy, age at menarche, age at menopause, pregnancy history, breastfeeding at least 1 month, and hormone therapy); effect-modifier variables (physical activity, BMI, and w/h ratio), when not evaluated as effect modifier variables, were adjusted as a covariate; when stratified via waist circumference, w/h ratio was not adjusted
  4. bParticipants stratified by BMI as non-obese (BMI < 30, n = 3675) or obese (BMI ≥ 30, n = 1704); interaction test presented for the effect of BMI on the association between breast cancer and rs560887 (effect size −0.38, p-value 0.28)
  5. cParticipants stratified by waist circumference as non-obese (waist ≤88 cm; n = 3042) or obese (waist >88 cm; n = 2337); interaction test presented for the effect of waist circumference on the association between breast cancer and rs560887 (effect size −0.55, p-value 0.13)
  6. dParticipants stratified by w/h as non-obese (w/h ≤ 0.85; n = 3712) or obese (w/h > 0.85; n = 1667); interaction tests presented for the effect of w/h on the association between breast cancer and rs560887 (effect size −0.57, p-value 0.11) and rs35767 (effect size 0.54, p-value 0.01)
  7. eParticipants stratified by dietary fat intake as non-obese (< 40% calories from fat; n = 4325) or obese (≥ 40% calories from fat; n = 1054); interaction test presented for the effect of dietary fat intake on the association between breast cancer and rs560887 (effect size −0.45, p-value 0.26)
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BMC Cancer

ISSN: 1471-2407

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