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.
Campa
Daniele
D
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Hüsing
Anika
A
McKay
James D
JD
Sinilnikova
Olga
O
Vogel
Ulla
U
Tjønneland
Anne
A
Overvad
Kim
K
Stegger
Jakob
J
Clavel-Chapelon
Françoise
F
Chabbert-Buffet
Nathalie
N
Fagherazzi
Guy
G
Trichopoulou
Antonia
A
Zylis
Dimosthenis
D
Oustoglou
Erifili
E
Rohrmann
Sabine
S
Teucher
Birgit
B
Fisher
Eva
E
Boeing
Heiner
H
Masala
Giovanna
G
Krogh
Vittorio
V
Sacerdote
Carlotta
C
Panico
Salvatore
S
Tumino
Rosario
R
Onland-Moret
N Charlotte
NC
van Gils
Carla H
CH
Bueno-de-Mesquita
H Bas
HB
Lund
Eiliv
E
Chirlaque
María Dolores
MD
Sala
Núria
N
Quirós
José Ramon
JR
Ardanaz
Eva
E
Amiano
Pilar
P
Molina-Montes
Esther
E
Hallmans
Göran
G
Lenner
Per
P
Travis
Ruth C
RC
Key
Timothy J
TJ
Wareham
Nick
N
Khaw
Kay-Tee
KT
Rinaldi
Sabina
S
Slimani
Nadia
N
Chajes
Veronique
V
Siddiq
Afshan
A
Riboli
Elio
E
Kaaks
Rudolf
R
Canzian
Federico
F
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