Table 4.
Association between instrumental genetic variables for sedentary time (per standard deviation in percent time spent sedentary) and risk of breast cancer
| Type of breast cancer | N cases (vs. 54,452 controls) | Odds ratios (95% CI) a | P for heterogeneity b |
|---|---|---|---|
|
| |||
| Invasive cancers | |||
|
| |||
| All invasive | 69,838 | 1.20 (0.93–1.55) | 0.962 |
| Pre/perimenopausal | c 23,999 | 1.22 (0.78–1.90) | 0.589 |
| Postmenopausal | d45,839 | 1.21 (0.89–1.65) | 0.983 |
|
| |||
| By receptor status | |||
|
| |||
| ER+ | 46,528 | 1.19 (0.90–1.57) | 0.992 |
| ER− | 11,246 | 1.43 (0.90–2.26) | 0.926 |
| PR+ | 34,891 | 1.19 (0.87–1.63) | 0.386 |
| PR− | 16,432 | 1.40 (0.94–2.09) | 0.435 |
| HER2+ | 6,945 | 1.17 (0.67–2.06) | 0.718 |
| HER2− | 33,214 | 1.27 (0.93–1.74) | 0.955 |
|
| |||
| Combined hormone receptor- and/or HER2-defined subtypes | |||
|
| |||
| ER+ or PR+; HER2+ | 4,816 | 0.86 (0.44–1.67) | 0.585 |
| ER+ or PR+; HER2− | 27,874 | 1.12 (0.80–1.56) | 0.801 |
| ER−; PR−; HER2+ | 1,974 | 1.94 (0.71–5.25) | 0.646 |
| ER−; PR−; HER2− | 4,964 | 2.04 (1.06–3.93) | 0.500 |
| ER− and PR− (all) | 9,215 | 1.77 (1.07–2.92) | 0.819 |
|
| |||
| By morphology | |||
|
| |||
| Ductal | 42,223 | 1.21 (0.91–1.62) | 0.992 |
| Lobular | 8,795 | 1.12 (0.66–1.91) | 0.695 |
|
| |||
| By stage at diagnosis | |||
|
| |||
| Stage I | 17,583 | 1.62 (0.99–2.65) | 0.187 |
| Stage II | 15,992 | 1.23 (0.79–1.90) | 0.820 |
| Stage III/IV | 4,553 | 0.91 (0.45–1.84) | 0.640 |
|
| |||
| By tumour grade | |||
|
| |||
| Grade 1/2 | 34,647 | 1.15 (0.84–1.57) | 0.901 |
| Grade 3 | 16,432 | 1.32 (0.88–1.97) | 0.967 |
|
| |||
| In situ cancers | |||
|
| |||
| All in situ | 6,667 | 1.75 (1.00–3.07) | 0.933 |
| Ductal carcinoma in situ | 3,510 | 2.11 (0.99–4.49) | 0.487 |
Abbreviations: CI, confidence interval; ER+/−, oestrogen receptor positive/negative; GWAS, genome wide association study; HER2+/−, human epidermal growth factor receptor 2 positive/negative; PR+/−, progesterone receptor positive/negative; SNP, single nucleotide polymorphism.
Causal odds ratios were estimated by inverse-variance weighted Mendelian randomization, using six SNPs identified in a GWAS of accelerometer-measured movement traits by Doherty et al (9)
p-value associated with the heterogeneity test statistic (Cochran’s Q statistic) measuring heterogeneity of causal effects between SNPs
vs pre/perimenopausal controls (n=17,686), assigned using age (<50 years) if menopause status was unknown
vs postmenopausal controls (n=36,766), assigned using age (≥50 years) if menopause status was unknown