The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk.
BACKGROUND
The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC).


METHODS
we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk.


CONCLUSIONS
In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Daniele
D
Campa
Anika
A
Hüsing
James D
JD
McKay
Olga
O
Sinilnikova
Ulla
U
Vogel
Anne
A
Tjønneland
Kim
K
Overvad
Jakob
J
Stegger
Françoise
F
Clavel-Chapelon
Nathalie
N
Chabbert-Buffet
Guy
G
Fagherazzi
Antonia
A
Trichopoulou
Dimosthenis
D
Zylis
Erifili
E
Oustoglou
Sabine
S
Rohrmann
Birgit
B
Teucher
Eva
E
Fisher
Heiner
H
Boeing
Giovanna
G
Masala
Vittorio
V
Krogh
Carlotta
C
Sacerdote
Salvatore
S
Panico
Rosario
R
Tumino
N Charlotte
NC
Onland-Moret
Carla H
CH
van Gils
H Bas
HB
Bueno-de-Mesquita
Eiliv
E
Lund
María Dolores
MD
Chirlaque
Núria
N
Sala
José Ramon
JR
Quirós
Eva
E
Ardanaz
Pilar
P
Amiano
Esther
E
Molina-Montes
Göran
G
Hallmans
Per
P
Lenner
Ruth C
RC
Travis
Timothy J
TJ
Key
Nick
N
Wareham
Kay-Tee
KT
Khaw
Sabina
S
Rinaldi
Nadia
N
Slimani
Veronique
V
Chajes
Afshan
A
Siddiq
Elio
E
Riboli
Rudolf
R
Kaaks
Federico
F
Canzian
D000273:Adipose Tissue; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D011110:Polymorphism, Genetic; D012306:Risk
C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins