Reference
Complete the bibliographic reference for the article according to AJE format.

Category of HuGE information
Specify the types of information (from the list below) available in the article:

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

1. Prevalence of gene variant
2. Gene-disease association

Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study

Gene(s)
Identification of the following:

1. Gene name
2. Chromosome location
3. Gene product/function
4. Alleles
5. OMIM #
6. GDPInfo link

1. Gene name: IGF1

2. Chromosome location: 12q22

3. Gene product/function: Glucocerebrosidase is a lysosomal enzyme that hydrolyzes glucocerebroside to glucose and ceramide. Deficiency of glucocerebrosidase results in accumulation of glucocerebroside in macrophages, causing multiorgan involvement.

4. Alleles:IGF1 gene product is a 70-amino acid polypeptide transcribed by two promoters. IGF1 mainly synthesized by the liver. It presents in circulation and binds to specific IGF binding protein (BP). IGF1 stimulates skeletal muscle hypertrophy and a switch to glycolytic metabolism by activating the calcium calmodulin-dependent phosphatase calcineurin and inducing the nuclear translocation of transcription factor NFATC1. In humans, IGF1 polymorphisms have been associated with type-2 diabetes, cardiovascular disease, Alzheimer disease, low birth weight, insulin resistant, prostate cancer and breast cancer.

   • Alleles: There are ten IGF1 alleles, (CA)11, (CA)13, (CA)16, (CA)17, (CA)18, (CA)19, (CA)20, (CA)21, (CA)22, (CA)23
     
5. OMIM#: 147440
6. Go to GDPInfo Genes A-Z result

Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)

N/A

Health outcome(s)
Identification of the major health outcome(s) studied

1. Case-control
2. Cohort 
3. Cross-sectional
4. Descriptive or case series
5. Clinical trial
6. Population screening

1. Case-control study (population-based)

Case definition
For study designs 2, 3, and 6, the following are defined, where available:

1. Case selection criteria
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

1. Disease case definition: All cases were newly diagnosed; aged 25-64 years during 1996-1998; Shanghai permanent residents. Tissue slides were reviewed by two senior pathologists.
2. Exclusion criteria: Unavailable blood samples; refusal; death prior to interview; inability to locate
3. Gender: Female
4. Race/ethnicity: Chinese
5. Age: 25-64 years
6. Time period: 1996-1998
7. Geographic location: Shanghai, China
8. Number of participants: 1,041 cases (87.3% of total eligible)

Control definition  
For study design 1, the following are defined, if available. 

1. Control selection criteria
2. Matching variables
3. Exclusion criteria 
4. Gender
5. Race/ethnicity
6. Age
7. Time period
8. Geographic location
9. Number of participants

1. Control selection criteria: Randomly selected from general female Shanghai population
2. Matching variables: Frequency-matched by 5-year age group
3. Exclusion criteria: Unavailable blood samples; refusal
4. Gender: Female
5. Race/ethnicity: Chinese
6. Age: 25-64 years
7. Time period: 1996-1998
8. Geographic location: Shanghai, China
9. Number of participants: 1,086 (82.9% of total eligible)

Cohort definition
For study designs 2, 3, and 6, define the following if available:

1. Cohort selection criteria
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

1. Cohort selection criteria: N/A
2. Exclusion criteria: N/A
3. Gender: N/A
4. Race/ethnicity: N/A
5. Age: N/A
6. Time period: N/A
7. Geographic location: N/A
8. Number of participants: N/A

1. Environmental factor
2. Exposure assessment
3. Exposure definition
4. Number of participants with exposure data (%
   of total eligible)

1. Environmental factor: N/A
2. Exposure assessment: N/A
3. Exposure definition:  N/A
4. Number of Participants with exposure data: N/A

1. Gene
2. DNA source
3. Methodology
4. Number of participants genotyped (% of total eligible) 

1. Gene: IGF1

2. DNA source: peripheral blood

3. Genotyping method: PCR, sequencing

4. Number of participants genotyped: 1,041 cases (87.3% of total eligible) and 1,086 controls (82.9%) were genotyped

1. Subjects who were heterozygous or homozygous for an IGF1 polymorphism were compared to those who did not carry the polymorphism.
2. Conditional logistic regression models were used to estimate odds ratio and 95% confidence interval of IGF1 genotypes, adjusted for potential confounders.
3. In tera ction analysis for association of breast cancer with IGF1 genotypes and plasma IGF1.
4. Meta-analysis

All analysis was appropriate to address the relevant questions.

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

1. Prevalence of gene variant (attached as Table 1-2)
   Ten IGF1 alleles were detected in this study. Six common alleles of (CA)17, (CA)18, (CA)19, (CA)20, (CA)21 and (CA)22 repeats constituted 98.9% of all alleles in the cases and 99.5% in the controls. 62.6% of cases and 58% of controls were heterozygous for (CA)19 allele
   
   
2. Gene-disease association (attached as Table 3-5). Genotypes with any copies of (CA)17 or (CA)19 allele were associated with a significantly decreased (OR=0.8, 95% CI:0.64-1.00) or increased (OR=1.23, 95% CI:1.04-1.47) risk of breast cancer, respectively. The genotypes with any rare alleles were also associated with an increased risk of breast cancer (OR=1.92, 95% CI:0.92-4.02).This study also confirmed the previous studies that plasma IGF1, IGF1I and IGFBP-3 were associated with breast cancer risk; No association was found between IGF1 genotype and plasma IGF; Meta analysis showed that IGF1 genotypes containing the (CA)19 allele were consistently associated with increased risk of breast cancer.
   • Table 1
   • Table 2
   • Table 3
   • Table 4
   • Table 5
   • Table 6

1. The genotype with (CA)19 allele was positively associated with breast cancer risk.
2. The genotype with (CA)17 was negatively associated with breast cancer risk.
3. No association between plasma IGF1 levels and IGF1 genotypes.

Comments
Provide additional insight, including methodologic issues and/or concerns about the study

1. Plasma IGF was only obtained at one time point, may not reflect its long-term level,
2. Blood samples were obtained after cancer diagnosis. The presence of tumor might have affected the level of plasma IGF1, IGF1I and IGFBP-3.
3. Positive association of breast cancer risk with (CA)19 allele in this study, carrier rates of (CA)19 allele were 62.6% and 58% in cases and controls in this population.

The population attributable risk percents (PARP) of (CA)19 genotype were 9.2% in heterozygous and 11.4% in homozygous in all subjects.