Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.
CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.
Chen
Chu
C
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Mailstop M5-C800, P.O. Box 19024, Seattle, WA 98109-1024, USA. cchen@fhcrc.org
Sakoda
Lori C
LC
Doherty
Jennifer A
JA
Loomis
Melissa M
MM
Fish
Sherianne
S
Ray
Roberta M
RM
Lin
Ming Gang
MG
Fan
Wenhong
W
Zhao
Lue Ping
LP
Gao
Dao Li
DL
Stalsberg
Helge
H
Feng
Ziding
Z
Thomas
David B
DB
D000328:Adult; D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016504:Breast Self-Examination; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005348:Fibrocystic Breast Disease / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
D001141:Aromatase