Background
Methods
Malmö diet and cancer study
Study population
Levels of vitamin D
Selecting SNPs
Statistical methods
Results
Potential confounders in cases and control subjects
Factor | Category | Study population with SNP data (%) | Study population with data on vitamin D (%) | ||
---|---|---|---|---|---|
Control subjects (n = 3193) | Cases (n = 865) | Control subjects (n = 643) | Cases (n = 700) | ||
Age, years |
Mean ± SD
|
57.4 ± 6.3
|
56.6 ± 7.3
|
57.0 ± 7.3
|
56.9 ± 7.2
|
Season of inclusion in MDCS | January–March | 33.1 | 28.8 | 29.9 | 29.9 |
April–June | 19.0 | 24.7 | 24.0 | 23.9 | |
July–September | 18.0 | 22.8 | 21.3 | 21.9 | |
October–December | 29.9 | 23.7 | 24.9 | 24.4 | |
Education | O-level college (7–9 years) | 73.6 | 66.5 | 68.0 | 67.7 |
A-level college (11–12 years) | 6.8 | 7.1 | 7.3 | 7.3 | |
University | 19.4 | 26.1 | 24.7 | 24.7 | |
Type of occupation | Manual labour worker | 39.6 | 32.7 | 38.7 | 34.4 |
Non-manual labour worker | 52.5 | 60.6 | 53.8 | 58.6 | |
Employer/self-employed | 6.9 | 5.7 | 7.5 | 5.7 | |
Missing | 0.9 | 1.0 | 0.0 | 1.3 | |
Married/co-habitating | No | 31.0 | 33.5 | 32.0 | 34.0 |
Yes | 69.0 | 66.5 | 68.0 | 66.0 | |
Age at menarche, years | < 12 | 6.2 | 7.6 | 4.5 | 7.3 |
12–15 | 67.2 | 67.3 | 68.9 | 67.1 | |
> 15 | 25.6 | 23.9 | 26.0 | 24.4 | |
Missing | 0.9 | 1.2 | 0.6 | 1.1 | |
Parity | Nulliparous | 12.0 | 14.1 | 11.2 | 13.6 |
One child | 21.4 | 19.5 | 22.4 | 19.3 | |
Two children | 40.6 | 44.7 | 40.9 | 44.1 | |
Three children or more | 22.8 | 19.5 | 22.7 | 20.6 | |
Missing | 3.1 | 2.1 | 2.8 | 2.4 | |
Age at first birth, years | Nulliparous | 12.0 | 14.1 | 11.2 | 13.6 |
≤ 20 | 16.5 | 14.9 | 17.9 | 13.6 | |
21–24 | 28.2 | 27.3 | 27.7 | 27.7 | |
25–29 | 29.1 | 28.7 | 28.6 | 30.1 | |
≥ 30 | 11.1 | 12.9 | 11.8 | 12.6 | |
Missing | 3.1 | 2.1 | 2.8 | 2.4 | |
Age at menopause, years | Pre-/peri-menopause | 27.2 | 35.6 | 32.5 | 33.1 |
< 45 | 9.8 | 9.0 | 8.6 | 9.4 | |
45–53 | 45.3 | 39.5 | 42.6 | 41.6 | |
> 53 | 16.0 | 13.8 | 14.9 | 13.7 | |
Missing | 1.7 | 2.1 | 1.4 | 2.1 | |
Exposure to oral contraceptives | No | 54.3 | 45.9 | 50.1 | 48.6 |
Yes | 45.7 | 54.0 | 49.9 | 51.3 | |
Exposure to hormone replacement therapy (HRT) | No (pre-menopausal) | 22.0 | 28.4 | 26.3 | 25.7 |
No (post-menopausal) | 59.8 | 44.5 | 53.3 | 45.7 | |
Oestrogen only | 7.6 | 7.4 | 9.2 | 7.6 | |
Progesterone only | 0.6 | 1.2 | 0.9 | 1.3 | |
Combined HRT | 9.4 | 18.3 | 9.8 | 19.4 | |
Height, m | ≤ 1.59 | 24.6 | 20.6 | 23.2 | 20.3 |
1.60–1.69 | 58.1 | 61.4 | 59.1 | 61.6 | |
≥ 1.70 | 17.2 | 18.0 | 17.7 | 18.1 | |
Body mass index, kg/m2
| < 25 | 53.3 | 50.1 | 51.8 | 50.6 |
≥ 25 to < 30 | 33.6 | 34.5 | 36.1 | 33.3 | |
≥ 30 | 13.0 | 15.5 | 12.1 | 16.1 | |
Alcohol consumption | Not in last year | 11.4 | 9.7 | 11.4 | 10.4 |
Some in last year | 12.7 | 11.2 | 12.4 | 11.4 | |
Some in last month | 75.6 | 78.8 | 75.9 | 78.0 | |
Smoking | Never | 46.8 | 43.0 | 42.5 | 44.0 |
Current | 26.7 | 26.7 | 27.8 | 26.6 | |
Ex-smoker | 26.4 | 30.3 | 29.7 | 29.4 |
SNPs and risk of low vitamin D level
SNP (GWAS SNP) | Risk of low vitamin D | Risk of breast cancer | ||||
---|---|---|---|---|---|---|
Allele | Frequency of low/high vitamin Da (n = 1343) | Crude OR of low vitamin D (95% CI) | Adjusted ORb of low vitamin D (95% CI) | Cases/control subjects (n = 4058) | Crude OR (95% CI) | Adjusted ORb (95% CI) |
rs12239582 (rs12144344) | ||||||
CC | 224/188 | 1.00 | 1.00 | 290/986 | 1.00 | 1.00 |
CA | 344/336 | 0.86 (0.67–1.10) | 0.87 (0.67–1.12) | 412/1604 | 0.87 (0.74–1.04) | 0.82 (0.68–0.99) |
AA | 116/135 | 0.72 (0.53–0.99) | 0.72 (0.52–1.00) | 163/600 | 0.92 (0.74–1.15) | 0.93 (0.73–1.17) |
Missing | – | – | – | 0/3 | – | – |
rs705117 | ||||||
CC | 504/486 | 1.00 | 1.00 | 657/2376 | 1.00 | 1.00 |
CT | 164/168 | 0.94 (0.73–1.21) | 0.94 (0.73–1.22) | 194/762 | 0.92 (0.77–1.10) | 0.86 (0.71–1.05) |
TT | 16/5 | 3.06 (1.11–8.44) | 3.38 (1.20–9.49) | 14/55 | 0.92 (0.51–1.67) | 0.94 (0.49–1.81) |
rs7041 | ||||||
AA | 213/270 | 1.00 | 1.00 | 332/1149 | 1.00 | 1.00 |
AC | 341/308 | 1.40 (1.11–1.78) | 1.39 (1.09–1.77) | 397/1521 | 0.90 (0.77–1.07) | 0.88 (0.74–1.05) |
CC | 130/81 | 2.03 (1.46–2.83) | 2.12 (1.51–2.99) | 136/522 | 0.90 (0.72–1.13) | 0.89 (0.70–1.13) |
Missing | – | – | – | 0/1 | – | – |
rs2282679 (rs17467825) | ||||||
GG | 342/397 | 1.00 | 1.00 | 480/1734 | 1.00 | 1.00 |
GT | 278/230 | 1.40 (1.12–1.76) | 1.42 (1.13–1.80) | 326/1222 | 0.96 (0.82–1.13) | 0.98 (0.83–1.16) |
TT | 62/29 | 2.45 (1.56–3.95) | 2.51 (1.56–4.05) | 57/229 | 0.90 (0.66–1.22) | 0.91 (0.66–1.27) |
Missing | 2/3 | – | – | 2/8 | – | – |
rs10485165 | ||||||
TT | 515/501 | 1.00 | 1.00 | 650/2385 | 1.00 | 1.00 |
TC | 153/144 | 1.04 (0.80–1.35) | 1.03 (0.79–1.34) | 194/735 | 0.97 (0.81–1.16) | 0.99 (0.82–1.20) |
CC | 16/14 | 1.10 (0.53–2.29) | 1.04 (0.49–2.21) | 21/73 | 1.06 (0.65–1.73) | 1.00 (0.60–1.74) |
rs198300 (rs156299) | ||||||
GG | 218/229 | 1.00 | 1.00 | 295/1134 | 1.00 | 1.00 |
GA | 344/319 | 1.13 (0.89–1.44) | 1.08 (0.84–1.38) | 430/1513 | 1.09 (0.92–1.29) | 1.10 (0.91–1.30) |
AA | 122/111 | 1.16 (0.84–1.59) | 1.09 (0.79–1.52) | 140/545 | 0.99 (0.79–1.24) | 0.96 (0.75–1.22) |
Missing | – | – | – | 0/1 | – | – |
rs4751058 | ||||||
AA | 496/460 | 1.00 | 1.00 | 614/2286 | 1.00 | 1.00 |
AG | 174/183 | 0.88 (0.69–1.13) | 0.88 (0.68–1.13) | 234/828 | 1.05 (0.89–1.25) | 1.05 (0.88–1.27) |
GG | 14/16 | 0.81 (0.39–1.68) | 0.77 (0.36–1.63) | 17/79 | 0.80 (0.47–1.36) | 0.66 (0.38–1.17) |
rs12295888 (rs12287212) | ||||||
CC | 270/296 | 1.00 | 1.00 | 367/1384 | 1.00 | 1.00 |
CT | 321/302 | 1.16 (0.93–1.46) | 1.22 (0.96–1.54) | 402/1435 | 1.06 (0.90–1.24) | 1.05 (0.88–1.24) |
TT | 93/61 | 1.67 (1.16–2.40) | 1.80 (1.24–2.63) | 96/373 | 0.97 (0.75–1.25) | 0.93 (0.71–1.23) |
Missing | – | – | – | 0/1 | – | – |
rs1007392 | ||||||
GG | 231/267 | 1.00 | 1.00 | 325/1184 | 1.00 | 1.00 |
GA | 337/310 | 1.26 (0.99–1.59) | 1.31 (1.03–1.67) | 417/1543 | 0.99 (0.84–1.16) | 0.99 (0.83–1.18) |
AA | 115/82 | 1.62 (1.16–2.26) | 1.78 (1.26–2.52) | 123/462 | 0.97 (0.77–1.23) | 0.91 (0.71–1.17) |
Missing | 1/0 | – | – | 0/4 | – | – |
rs2060793 (rs10741657) | ||||||
AA | 246/194 | 1.00 | 1.00 | 283/1040 | 1.00 | 1.00 |
AG | 328/323 | 0.80 (0.63–1.02) | 0.78 (0.61–1.00) | 418/1544 | 1.00 (0.84–1.18) | 1.10 (0.92–1.33) |
GG | 110/142 | 0.61 (0.45–0.84) | 0.58 (0.42–0.81) | 164/606 | 1.00 (0.80–1.24) | 1.04 (0.82–1.32) |
Missing | – | – | – | 0/3 | – | – |
rs7944926 (rs12785878) | ||||||
AA | 297/343 | 1.00 | 1.00 | 423/1436 | 1.00 | 1.00 |
AG | 299/272 | 1.27 (1.01–1.59) | 1.30 (1.03–1.64) | 366/1400 | 0.89 (0.76–1.04) | 0.91 (0.77–1.08) |
GG | 88/44 | 2.31 (1.56–3.43) | 2.39 (1.59–3.59) | 76/356 | 0.73 (0.55–0.95) | 0.77 (0.57–1.02) |
Missing | – | – | – | 0/1 | – | – |
rs3829251 | ||||||
AA | 402/435 | 1.00 | 1.00 | 545/1954 | 1.00 | 1.00 |
AG | 242/210 | 1.25 (0.99–1.57) | 1.30 (1.02–1.64) | 287/1079 | 0.95 (0.81–1.12) | 0.99 (0.83–1.18) |
GG | 40/14 | 3.09 (1.65–5.77) | 3.26 (1.72–6.17) | 33/160 | 0.74(0.50–1.09) | 0.77 (0.51–1.16) |
rs2302190 | ||||||
CC | 451/466 | 1.00 | 1.00 | 566/2122 | 1.00 | 1.00 |
CT | 211/176 | 1.24 (0.98–1.57) | 1.24 (0.97–1.58) | 268/955 | 1.05(0.89–1.24) | 1.09 (0.91–1.30) |
TT | 20/13 | 1.59 (0.78–3.23) | 1.45 (0.69–3.02) | 28/109 | 0.96 (0.63–1.47) | 0.99 (0.62–1.58) |
Missing | 2/4 | – | – | 3/7 | – | – |
SNPs and overall breast cancer risk
SNPs and breast cancer risk in different strata of serum vitamin D
SNP (proxy for GWAS) | Low vitamin Da
| High vitamin Da
| |||
---|---|---|---|---|---|
Allele | Frequency in cases/control subjects (n = 684) | ORb of breast cancer (95% CI) |
p Value for interaction | Frequency in cases/control subjects (n = 659) | ORb of breast cancer (95% CI) |
rs12239582 (rs12144344) | |||||
CC | 127/97 | 1.00 | 99/89 | 1.00 | |
CA | 176/168 | 0.85 (0.59–1.21) | 0.73 | 164/172 | 0.91 (0.62–1.33) |
AA | 60/56 | 0.83 (0.52–1.34) | 0.30 | 74/61 | 1.16 (0.72–1.87) |
rs705117 | |||||
CC | 278/226 | 1.00 | 251/235 | 1.00 | |
CT | 76/88 | 0.65 (0.45–0.95) | 0.28 | 84/84 | 0.87 (0.60–1.27) |
TT | 9/7 | 1.14 (0.41–3.22) | 0.36 | 2/3 | 0.45 (0.66–3.11) |
rs7041 | |||||
AA | 120/93 | 1.00 | 141/129 | 1.00 | |
AC | 169/172 | 0.70 (0.48–1.00) | 0.14 | 161/147 | 1.05 (0.74–1.47) |
CC | 74/56 | 1.11 (0.69–1.76) | 0.15 | 35/46 | 0.65 (0.38–1.11) |
rs2282679 (rs17467825) | |||||
GG | 174/168 | 1.00 | 209/188 | 1.00 | |
GT | 155/123 | 1.25 (0.89–1.75) | 0.16 | 113/117 | 0.91 (0.65–1.29) |
TT | 33/29 | 1.21 (0.68–2.16) | 0.69 | 14/15 | 0.92 (0.42–2.04) |
Missing | 1/1 | – | – | 1/2 | – |
rs10485165 | |||||
TT | 267/248 | 1.00 | 262/239 | 1.00 | |
TC | 88/65 | 1.34 (0.91–1.98) | 0.08 | 67/77 | 0.83 (0.56–1.22) |
CC | 8/8 | 0.94 (0.32–2.78) | 0.79 | 8/6 | 1.11 (0.36–3.40) |
rs198300 (rs156299) | |||||
GG | 126/92 | 1.00 | 110/119 | 1.00 | |
GA | 184/160 | 0.82 (0.57–1.18) | 0.25 | 165/154 | 1.06 (0.74–1.52) |
AA | 53/69 | 0.53 (0.33–0.87) | <0.01 | 62/49 | 1.38 (0.85–2.23) |
rs4751058 | |||||
AA | 267/229 | 1.00 | 235/225 | 1.00 | |
AG | 89/85 | 0.91 (0.63–1.329 | 0.37 | 96/87 | 1.06 (0.74–1.52) |
GG | 7/7 | 1.00 (0.33–3.03) | 0.42 | 6/10 | 0.47 (0.16–1.38) |
rs12295888 (rs12287212) | |||||
CC | 146/124 | 1.00 | 157/139 | 1.00 | |
CT | 169/152 | 0.94 (0.66–1.33) | 0.88 | 154/148 | 0.86 (0.61–1.20) |
TT | 48/45 | 1.01 (0.60–1.67) | 0.33 | 26/35 | 0.65 (0.36–1.17) |
rs1007392 | |||||
GG | 129/102 | 1.00 | 140/127 | 1.00 | |
GA | 177/160 | 0.87 (0.61–1.25) | 0.71 | 159/151 | 0.91 (0.64–1.29) |
AA | 57/58 | 0.81 (0.50–1.30) | 0.98 | 38/44 | 0.79 (0.47-1.34) |
Missing | 0/1 | – | – | – | |
rs2060793 (rs10741657) | |||||
AA | 134/112 | 1.00 | 89/105 | 1.00 | |
AG | 168/160 | 0.95 (0.67–1.35) | 0.10 | 174/149 | 1.35 (0.93–1.97) |
GG | 61/49 | 0.99 (0.61–1.60) | 0.44 | 74/68 | 1.31 (0.83–2.08) |
rs7944926 (rs12785878) | |||||
AA | 167/130 | 1.00 | 180/163 | 1.00 | |
AG | 158/141 | 0.88 (0.62–1.24) | 0.75 | 137/135 | 0.93 (0.66–1.29) |
GG | 38/50 | 0.58 (0.35–0.98) | 0.49 | 20/24 | 0.78 (0.40–1.51) |
rs3829251 | |||||
AA | 218/184 | 1.00 | 222/213 | 1.00 | |
AG | 126/116 | 0.95 (0.68–1.34) | 0.56 | 110/100 | 1.07 (0.76–1.51) |
GG | 19/21 | 0.74 (0.37–1.49) | 0.62 | 5/9 | 0.57 (0.18–1.79) |
rs2302190 | |||||
CC | 236/215 | 1.00 | 229/237 | 1.00 | |
CT | 114/97 | 1.03 (0.73–1.47) | 0.49 | 97/79 | 1.27 (0.88–1.84) |
TT | 12/8 | 1.36 (0.51–3.60) | 0.52 | 9/4 | 2.11 (0.61–7.30) |
Missing | 1/1 | – | – | 2/2 | – |