title: Family history of cancer and the risk of squamous cell carcinoma of oesophagus: a case-control study in Kashmir, India.
abstract: BACKGROUND
  Only a few studies have examined the association between family history of cancer (FHC) and the risk of oesophageal squamous cell carcinoma (ESCC) in high incidence areas of ESCC. We conducted a case-control study to evaluate the relationship between FHC and ESCC risk in Kashmir, India, with analysis of detailed epidemiological data and information on multiple gene polymorphisms.
  
  
  METHODS
  We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 703 histopathologically confirmed ESCC cases and 1664 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).
  
  
  RESULTS
  Participants who had FHC showed a strong association with ESCC risk, and the risk was stronger when first-degree relatives (FDRs) had FHC (OR=6.8; 95% CI=4.6-9.9). Having a sibling with a cancer showed the strongest association (OR=10.8; 95% CI=6.0-19.3), but having a child with a cancer was not associated with ESCC risk. A history of any cancer in the spouse was also associated with ESCC risk (OR=4.1; 95% CI=1.6-10.2). Those with two or more relatives with FHC were at a higher risk of ESCC. After restricting FHC to familial ESCC only, the above associations were strengthened, except when spouses were affected with ESCC (OR=2.5; 95% CI=0.7-8.9). When we examined the associations between several single-nucleotide polymorphisms and ESCC in those with and without FHC, the associations of variant genotypes in cytochrome P450 (CYP) 2C19 and CYP2D6 and the wild genotype of CYP2E1 with ESCC were much stronger in those with FHC. The FHC had an additive interaction with several risk factors of ESCC in this population.
  
  
  CONCLUSIONS
  Our results showed that FHC was strongly associated with ESCC risk in Kashmir. It seems both genetic factors and shared environment are involved in this association.
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
authors.forename: G A
authors.initials: GA
authors.lastname: Bhat
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
authors.forename: I A
authors.initials: IA
authors.lastname: Shah
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
authors.forename: R
authors.initials: R
authors.lastname: Rafiq
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
authors.forename: S
authors.initials: S
authors.lastname: Nabi
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
authors.forename: B
authors.initials: B
authors.lastname: Iqbal
authors.affiliation: Departments of Radiation Oncology, SK Institute of Medical Sciences, Soura Srinagar, 190011 India.
authors.forename: M M
authors.initials: MM
authors.lastname: Lone
authors.affiliation: 1] Surveillance and Health Services Research, American Cancer Society, Atlanta, GA, USA [2] Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, 14117 Iran.
authors.forename: F
authors.initials: F
authors.lastname: Islami
authors.affiliation: Tisch Cancer Institute and Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Boffetta
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
authors.forename: N A
authors.initials: NA
authors.lastname: Dar
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D000077277:Esophageal Squamous Cell Carcinoma; D005192:Family Health / Q000706:statistics & numerical data*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D019392:Cytochrome P-450 CYP2E1; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6