| BACKGROUND Gastric cancer (GC) is one of the common tumors in many countries. GC had a high incidence and mortality rate in the world and ranked second in mortality. Worldwide, gastric cancer patients increased 800,000 people each year. Most gastric cancer were present in the middle age and was particularly prevalent in the 40～60 age group, the average age was about 50 years old, only 5% of patients under 30 years of age. Gastric cancer was more common in men than in women , the incidence ratio of gastric cancer was close to 2:1, and the ratio was up to 3～4:1 in China. Gastric cancer was the most common cancer in China, accounting for about one-third of all cancers, and half of gastrointestinal tumors. According to the assessment reports for global common tumor incidence rates by WHO (2001), Chinese cancer accounts for more than 30% of the total incidence of global upper gastrointestinal tumor, the mortality rate of stomach cancer was higher, average annual mortality rate was 16/10~5 and to 60/10~5 in some high incidence areas, 16 million people died from gastric cancer patients each year. The morbidity of gastric cancer showed an upward trend in many areas in recent years. Henan province in China is one of the high incidence areas of gastric cancer, which standardized mortality rate was between 30/10~5～90/10~5.The survival rate of GC is still low; it seriously imperils the health and the livings of the people.The occurrence of gastric cancer is a result from the combined role of multiple factors, including environmental factors, especially Hp infection,dietary factors, life behavior,and the organism of internal factors, including genetic factors, social and psychological factors. In recent years, people had conducted extensive exploration. At present, most of researchers think that both environmental factors and heredity take a role in the etiology of GC, but most of studies emphasize only on environmental risk factors of GC, and to underestimate the role of genetic factors. Along with the in-depth understanding of the cause, more and more people are aware of the importance of genetic factors.AIMS To explore family aggregation of GC, heritability and mode of inheritance of GC, by population-based case control family study, and synthetically evaluate the role of genetic factor in the pathogenesis of gastric cancer.SUBJECTS AND METHODS All new GC cases diagnosed in Xin'an County from August 2003 to August 2005 were chosed as the probands, and all the members of the first and second grade relatives of probands' and their spouses' as controls form the study subjects. All the investigators had been trained strictly and the questionnaires were filled in a form of face-to-face interview. Data were then sorted and input into computer by EpiData 3.1 software with the establishment of a database and were checked twice. The segregate ratio and heritability were calculated to evaluate the genetic characteristics of GC. Then regressive logistic models were used to do complex segregation analysis on the data of GC pedigrees. Based on the equilibrium between probands' pedigrees and spouses' pedigrees, the incidence rates of gastric cancer in pedigree members of probands' and spouses' were compared separately. In complex segregation analysis, class A and class D regressive logistic models were fitted. SPSS (Statistics Package for Social Science, version13.0), and SAGE 5.3.1 were used in the analysis.RESULTS These pedigrees consisted of 42 patients of 902 individuals from 32 probands' pedigrees and 32 spouses' pedigrees. The prevalence of GC in first-degree relatives of probands(9.18%) was higher than that in controls(3.08%); the GCprevalence in second-degree relatives of probands(6.28%) was higher than that incontrols(1.88%) either.The ratio of male and female relatives sufered from GC inprobands was 9.55% and 6.03 % respectively, higher than that in controls (3.256%and 1.778% respectively).The age of onset for gastric cancer was concentrated in 65～75 years old. The averageage of onset for male patients was 64.00±15.96 years old, the average age of onsetfor male patients was64.19±11.54 years old, the difference was not statisticallysignificant (t=-0.047, P=0.963). The average ages of onset for gastric cancer patientswith and without family history of gastric cancer were 58.71±12.54 years and67.72±11.35years old, separately, the difference was statistically significant (t=2.421,P = 0.02).The family history of GC in cases was 35.6%, significantly higher than that incontrols (20.1%)(x~2=26.958, P =0.000).That indicated the family history of GCplayed a role in the occurrenceand and development of GC.The distribution of GC in the pedigrees of probands was different from that incontrols.The binomial distribution analysis showed that there was familial aggregationin the occurrence of GC in relatives of probands, compared theory cases with actualcases.Heritability in the first-degree and second-degree relatives of probands was54.75%±6.74% and 44.97%±11.85% by using Falconer model of susceptiblethreshold value, which indicated that genetic factors played a part in occurrence ofGC, but environmental factors might be more important.The segregate ratio of GC estimated of Li-Mantel-Gart was 0.039±0.022 , which wassignificantly lower than 0.25,and met the polygenic diseases. The results indicatedthat GC conformed to the characteristic of polygenic inheritance.In complex segregation analysis, SAGE-SEGREG software was used to fit severalgenetic model, including Mendelian inheritance(major gene, dominant, recessive,co-dominant) and non-Mendelian inheritance(non-transmitted, environment, general), and at last all Mendelian inheritances including major gene, dominant, recessive, were refused, while co-dominant inheritance was accepted, suggesting occurrence of GC may due to multi minigene effects , in which there may exist major gene effect, and common family environment.CONCLUSIONS1. Family history of GC is possibly a risk factor for GC that may make GC have an early age of onset.2. GC has the family aggregation phenomenon, namely, distribution of GC is not equality of opportunity by the probability distribution3. Genetic factors play a certain role in the incidence of GC , but environmental factors may be more important.4. GC conform to the characteristic of polygenic inheritance, namely, the occurrence of GC is a general effect which produces under certain environmental factors by multi minigene effects, in which there may exist major gene effect.5. We propose ,the families which have two or more than two cases died of gastric cancer in three generations be as high-risk families, the family members over 40 years old be as high-risk groups, regular screening and preventive intervention be conducted to achieve first prevention and secondary prevention. |
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